ÂÏÏËÓÈο ÛÙÔÌ·ÙÔÏÔÁÈο ¯ÚÔÓÈο ÂÏÏËÓÈη ÛÙÔÌ·ÙÔÏÔÁÈη ¯ÚÔÓÈη TOMO™ 57 ñ TEYXO™ 1 IANOYAPIO™ - MAPTIO™ 2013 ENTY¶O K§EI™TO AP. A¢. 520/92 £ÂÌÈÛÙÔÎÏ¤Ô˘˜ 38 106 78 Aı‹Ó· Kø¢IKO™ 6705 TPIMHNIAIA EK¢O™H E§§HNIKH™ O¢ONTIATPIKH™ OMO™¶ON¢IA™ ISSN 1011 - 4181 E¶I™THMONIKO ENTY¶O ME E£NIKH ANA°NøPI™H ºEK 431/2 Ù˘ 5 AÚÈÏ›Ô˘ 2005 T· E™X ‚Ú›ÛÎÔÓÙ·È Î·Ù·¯ˆÚË̤ӷ ÛÙÔÓ EıÓÈÎfi ™˘ÏÏÔÁÈÎfi K·Ù¿ÏÔÁÔ EÈÛÙËÌÔÓÈÎÒÓ ¶ÂÚÈÔ‰ÈÎÒÓ ÙÔ˘ EıÓÈÎÔ‡ K¤ÓÙÚÔ˘ TÂÎÌËÚ›ˆÛ˘ TA «E§§HNIKA ™TOMATO§O°IKA XPONIKA» ™TO ¢IA¢IKTYO To ¢ÈÔÈÎËÙÈÎfi ™˘Ì‚Ô‡ÏÈÔ Ù˘ EOO Î·È Ë ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹ ÙˆÓ «EÏÏËÓÈÎÒÓ ™ÙÔÌ·ÙÔÏÔÁÈÎÒÓ XÚÔÓÈÎÒÓ», ÂÎÙÈÌÒÓÙ·˜ ÙȘ ‰˘Ó·ÙfiÙËÙ˜ Ù˘ Û‡Á¯ÚÔÓ˘ ËÏÂÎÙÚÔÓÈ΋˜ Ù¯ÓÔÏÔÁ›·˜, ·ÔÊ¿ÛÈÛÂ, Ë ÙÚÈÌËÓÈ·›· ¤Î‰ÔÛË ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡ Ó· Á›ÓÂÙ·È ·ÔÎÏÂÈÛÙÈο ËÏÂÎÙÚÔÓÈο, Ì ·Ó¿ÚÙËÛË ÙˆÓ Ù¢¯ÒÓ ÛÙÔ ‰È·‰ÈÎÙ˘·Îfi ÙfiÔ Ù˘ EÏÏËÓÈ΋˜ O‰ÔÓÙÈ·ÙÚÈ΋˜ OÌÔÛÔÓ‰›·˜. HÏÂÎÙÚÔÓÈ΋ EÈÎÔÈÓˆÓ›· Î·È AÔÛÙÔÏ‹ EÈÛÙËÌÔÓÈÎÒÓ EÚÁ·ÛÈÒÓ ÛÙË ‰È‡ı˘ÓÛË [email protected] TOMO™ 57 IANOYAPIO™ - MAPTIO™ 2013 hellenic stomatological review HELLENIC DENTAL ASSOCIATION VOLUME 57, ISSUE 1, JANUARY - MARCH 2013 ISSN 1011 - 4181 1 EÏÏËÓÈ΋ O‰ÔÓÙÈ·ÙÚÈ΋ OÌÔÛÔÓ‰›· ÂÏÏËÓÈο ÛÙÔÌ·ÙÔÏÔÁÈο ¯ÚÔÓÈο I¢IOKTHTH™: EÏÏËÓÈ΋ O‰ÔÓÙÈ·ÙÚÈ΋ OÌÔÛÔÓ‰›· ¢IEY£YNTH™ ™YNTA•H™: I. °. T˙Ô‡Ù˙·˜ ™YNTAKTIKH E¶ITPO¶H: °. ¢Ô˘‚›ÙÛ·˜ º. ZÂÚ‚Ô‡-B¿Ï‚Ë H. K·Úη˙‹˜ °. ¶ÔÏ˘˙Ò˘ A. KÔÛÈÒÓË ¶. §·ÁÔ˘‚¿Ú‰Ô˜ °. MÔ˘ÓÙÔ‡Ú˘ X. ¶·ÍÈÌ·‰¿ §. ¶··ÁÈ·ÓÓÔ‡ÏË ¢. ™·ÎÂÏÏ¿ÚË º. T˙¤ÚÌÔ˜ B. TÔ›ÙÛÔÁÏÔ˘-£ÂÌÂÏ‹ ¢. T˙È·Ê¿˜ E¶IME§HTE™ ™YNTA•H™: M. AÓÙˆÓÈ¿‰Ô˘, E.T. º·ÚÌ¿Î˘ E¶IME§EIA EK¢O™H™: Œ‚ÂÏÈÓ M·Ì¿Ë Y¶EY£YNO™ EKTY¶ø™H™: TypeProduct B. & E. M·Ì¿Ë E¶E EÈÎÔ‡ÚÔ˘ 31 & ¶ÂÈÚ·ÈÒ˜ TËÏ.: (210) 32.14.904 ¢IAºHMI™EI™ - ¢HMO™IE™ ™XE™EI™: M. MÔÚʈÓÈÔ‡ - ™. °ÎfiÁη˜ TËÏ.: (210) 33.02.343 Fax: (210) 38.34.385 e-mail: [email protected] T· ™ÙÔÌ·ÙÔÏÔÁÈο XÚÔÓÈο Â›Ó·È ÙÔ Â›ÛËÌÔ ÂÈÛÙËÌÔÓÈÎfi ¤ÓÙ˘Ô Ù˘ EÏÏËÓÈ΋˜ O‰ÔÓÙÈ·ÙÚÈ΋˜ OÌÔÛÔÓ‰›·˜ Ô˘ ÂΉ›‰ÂÙ·È ·Ó¿ ÙÚ›ÌËÓÔ. EÙ‹ÛÈ· Û˘Ó‰ÚÔÌ‹: 0,01 e ™˘Ó‰ÚÔÌ‹ Â͈ÙÂÚÈÎÔ‡ 40 $ EK¢OTH™: Aı·Ó¿ÛÈÔ˜ K·ÙÛ›Î˘, ¶Úfi‰ÚÔ˜ E.O.O. E¢PA EK¢O™H™: £ÂÌÈÛÙÔÎÏ¤Ô˘˜ 38 - Aı‹Ó· 106 78 Kø¢IKO™: 6705 TËÏ.: (210) 38.13.380 Fax: (210) 38.34.385 e-mail: [email protected] TOMO™ 57, TEYXO™ 1 IANOYAPIO™ - MAPTIO™ 2013 ISSN 1011 - 4181 ¶EPIEXOMENA EPEYNHTIKH EP°A™IA ñ ÕÛÎÔË ÔÏ˘Ê·Ú̷Λ· ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÓÔÛËÌ¿ÙˆÓ ÙÔ˘ ÛÙfiÌ·ÙÔ˜. AÓ·‰ÚÔÌÈ΋ ÌÂϤÙË Û 458 ·ÛıÂÓ›˜. E.-M. K·ÏÔÁ‹ÚÔ˘, K.I. TfiÛÈÔ˜ Î·È A. ™ÎÏ·‚Ô‡ÓÔ˘ .........................9-17 £EMA K§INIKOY EN¢IAºEPONTO™ ñ KÏÈÓÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘¯ˆÙ‹˜ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜ ·fi Ô‰ÔÓÙÔÛÙÔȯ›Â˜. ¶·ÚÔ˘Û›·ÛË ÂÚÈÛÙ·ÙÈÎÔ‡ Î·È ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ó·ÛÎfiËÛË. M. ™ˆÙËÚ›Ô˘, N. ¶ÔÏ˘¯ÚÔÓ¿Î˘, º. ºÚ·ÁΛÛÎÔ˜ Î·È E. ™Ù·‡ÚÔ˘..............................................................................19-26 EN¢IAºEPOY™A ¶EPI¶Tø™H ñ H ¢È·Ù·ÙÈ΋ OÛÙÂÔÁ¤ÓÂÛË ÛÙËÓ ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋. ¶·ÚÔ˘Û›·ÛË ÂÚ›ÙˆÛ˘ Î·È ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜. X. ™Ô˘Ï›Ô˘, A. Z·‹, °. B·Á‰Ô‡ÙË Î·È º. T˙¤ÚÌÔ˜ ...................27-37 BIB§IO°PAºIKH ANA™KO¶H™H ñ MÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Î·È ÌÂÙ·ÊÔÚ¿ ÁÔÓȉ›ˆÓ ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ. £. KÔÓ‰‡Ï˘, E. ¶ÂÂÏ¿ÛË ..........................................................39-71 Hellenic Dental Association Hellenic Stomatological Review PROPRIETOR: Hellenic Dental Association EDITOR -IN- CHIEF: J. G. Tzoutzas EDITORIAL BOARD: G. Douvitsas F. Zervou-Valvi H. Karkazis G. Polyzois A. Kossioni P. Lagouvardos G. Mountouris H. Paximada L. Papagiannoulis D. Sakellari F. Tzerbos V. Topitsoglou-Themeli D. Tziafas PRODUCTION SUPERVISORS: M. Antoniadou, E.T. Farmakis COPY EDITOR: Evelin Babai PRODUCTION - PROMOTION: TypeProduct V. & E. Babai Ltd 32 Epikourou Str., Athens Hellas Phone#: (3210) 32.14.904 Fax#: (3210) 32.14.991 ADVERTISEMENTS - PUBLIC RELATIONS: M. Morfoniou - S. Gogas Phone#: (3210) 33.02.343 Fax: (3210) 38.34.385 e-mail: [email protected] Hellenic Stomatological Review is the official publication of the Hellenic Dental Association, published trimonthly. Annual subscription 40 $ USD PUBLISHER: Athanasios Katsikis President of the Hellenic Dental Association HEADQUARTERS 38 Themistokleous Str., Athens, 106 78 Phone#: (3210) 38.13.380 Fax#: (3210) 38.34.385 e-mail: [email protected] VOLUME 57, ISSUE 1 JANUARY - MARCH 2013 ISSN 1011 - 4181 CONTENTS CLINICAL INTEREST ñ Clinical management of epulis fissuratum: Case presentation and Literature Review. M. Sotiriou, N. Polychronakis, F. Fragiskos and E. Stavrou.............9-17 RESEARCH PAPER ñ Drug abuse and overuse in the management of oral diseases. Retrospective study in 458 patients. E.-M. Kalogirou, K. I. Tosios and A. Sklavounou...........................19-26 CASE REPORT ñ The Distraction Osteogenesis in pre-implant surgery. A case report and review of the literature. C. Souliou, C. Zappi, G. Bagdouti and F. Tzermpos .....................27-37 LITERATURE REVIEW ñ Mesenchymal stem cell transplantation and gene transfer for periodontal tissue regeneration. T. Kondylis, E. Pepelassi ...............................................................39-71 ™YNTAKTIKH ™E§I¢A H KÚ›ÛË Î·È ÛÙȘ ¢ËÌÔÛȇÛÂȘ H OÈÎÔÓÔÌÈ΋ KÚ›ÛË Î·È Ù· ·ÚÂÏÎfiÌÂÓ¿ Ù˘, Â›Ó·È ·Ó·ÌÂÓfiÌÂÓÔ Ó· ‰ËÌÈÔ˘ÚÁÔ‡Ó ÛÔ‚·Ú¿ ÚÔ‚Ï‹Ì·Ù· ÛÙËÓ ‰È·Î›ÓËÛË Ù˘ EÈÛÙËÌÔÓÈ΋˜ ÏËÚÔÊÔÚ›·˜, ÙËÓ ·ÓÙ·ÏÏ·Á‹ ·fi„ÂˆÓ Î·È ÙËÓ ÔÌ·Ï‹ ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ¯ÒÚˆÓ Î·È ÙˆÓ ÊÔÚ¤ˆÓ Ô˘ ·Ú¿ÁÔ˘Ó ‹ ÌÂÙ·‰›‰Ô˘Ó ÙË °ÓÒÛË. H OÈÎÔÓÔÌÈ΋ KÚÈÛË Ô˘ Ì·ÛÙ›˙ÂÈ ÙËÓ EÏÏ¿‰· ηٿ ÙËÓ ÙÂÏÂ˘Ù·›· ÂÓÙ·ÂÙ›·, ¤¯ÂÈ ‰ËÌÈÔ˘ÚÁ‹ÛÂÈ ÛÔ‚·Ú¿ ÚÔ‚Ï‹Ì·Ù· ÛÙËÓ ÔÌ·Ï‹ ‰ÈÂÍ·ÁˆÁ‹ Ù˘ ¤Ú¢ӷ˜ Î·È Î·Ù¿ Û˘Ó¤ÂÈ· Ì¿ÏÈÛÙ· ÛÙËÓ ·Ú·ÁˆÁ‹ ‰ËÌÔÛȇÛÂˆÓ Û ¤ÁÎÚÈÙ· EÏÏËÓÈο Î·È ¢ÈÂıÓ‹ EÈÛÙËÌÔÓÈο ŒÓÙ˘·. OÈ ‰˘ÛÎÔϛ˜ ÍÂΛÓËÛ·Ó ÚÈÓ ·fi Ï›Á· ¯ÚfiÓÈ· Ì ÙÔÓ ÂÚÈÔÚÈÛÌfi ‹ ·ÎÚÈ‚¤ÛÙÂÚ· ÙËÓ ·˘ÍË̤ÓË ‰˘ÛÎÔÏ›· Î·È ÙËÓ ·Ó·‚ÏËÙÈÎfiÙËÙ· Ô˘ ·ÚÔ˘ÛÈ¿ÛÙËΠÛÙËÓ ÚfiÛ‚·ÛË Û ÌÂÁ¿Ï· ÂÚ¢ÓËÙÈο ÚÔÁÚ¿ÌÌ·Ù·, ÙËÓ fiÏÔ Î·È ÈÔ ÔχÏÔÎË NÔÌÈο Î·È T˘Èο ‰È·‰Èηۛ·, ÁÈ· ÙËÓ ˘Ô‚ÔÏ‹ Î·È ÙËÓ ‰È·Î›ÓËÛË ÂÚ¢ÓËÙÈÎÒÓ ÚˆÙÔÎfiÏψÓ, ÙËÓ ÂÌÏÔ΋ fiÏÔ Î·È ÂÚÈÛÛÔÙ¤ÚˆÓ NfiÌˆÓ Î·È ¢È·Ù¿ÍÂˆÓ ÛÙË ‰È·‰Èηۛ· Ù˘ Û˘ÓÂÚÁ·Û›·˜ ÂÚ¢ÓËÙÈÎÔ‡ ÚÔÛˆÈÎÔ‡ ‹ ÙËÓ ÚÔÌ‹ıÂÈ· ÂÈÛÙËÌÔÓÈÎÔ‡ ÂÍÔÏÈÛÌÔ‡. ŒÊı·Û ̿ÏÈÛÙ· ̤¯ÚÈ Î·È ÙËÓ ·‰˘Ó·Ì›· ¿ÓÙÏËÛ˘ ÛÙÔȯ›ˆÓ Ù˘ ‰ÈÂıÓÔ‡˜ ‚È‚ÏÈÔÁÚ·Ê›·˜, ̤ۈ ÙˆÓ ËÏÂÎÙÚÔÓÈÎÒÓ ‚È‚ÏÈÔıËÎÒÓ, ÏfiÁˆ ‰È·ÎÔ‹˜ Ù˘ ¯ÚËÌ·ÙÔ‰fiÙËÛ˘ ‹ χÛ˘ ÙˆÓ Û˘Ì‚·ÙÈÎÒÓ Û¯¤ÛÂˆÓ Ì ¤ÁÎÚÈÙÔ˘˜ ÂΉÔÙÈÎÔ‡˜ Ô›ÎÔ˘˜ ÙÔ˘ Â͈ÙÂÚÈÎÔ‡. K·Ù¿ Ù· ÚÒÙ· ¯ÚfiÓÈ· Ô˘ Ë ÎÚ›ÛË ¤Î·Ó ÙËÓ ÂÌÊ¿ÓÈÛ‹ Ù˘, ÔÈ ÂÏÏËÓÈΤ˜ ‰ËÌÔÛȇÛÂȘ -ÙÔ˘Ï¿¯ÈÛÙÔÓ ÛÙÔ ¯ÒÚÔ ÙˆÓ O‰ÔÓÙÈ·ÙÚÈÎÒÓ EΉfiÛˆÓ- ¤‰ÂÈÍ·Ó Ó· ÌËÓ ÂËÚ¿˙ÔÓÙ·È Ô‡Ù ÔÛÔÙÈο, Ô‡Ù ÔÈÔÙÈο Î·È ÙÔ‡ÙÔ ‰ÈfiÙÈ ˘‹Ú¯Â ·ÎfiÌ· Ë Âʉڛ· ÁÓÒÛ˘ Î·È ÂÈÛÙËÌÔÓÈÎÒÓ ÛÙÔȯ›ˆÓ ·fi ·ÚÂÏıÔ‡Û˜ ÂÚ¢ÓËÙÈΤ˜ Î·È Û˘ÁÁÚ·ÊÈΤ˜ ‰Ú·ÛÙËÚÈfiÙËÙ˜. MÈ· ÛÂÈÚ¿ fï˜ ·fi ÁÂÁÔÓfiÙ· Ô˘ Û˘Ó¤‚ËÛ·Ó ¤ÎÙÔÙÂ, ÌÂÚÈο ·fi Ù· ÔÔ›· ·Í›˙ÂÈ Ó· ·Ó·ÊÂÚıÔ‡Ó ·Ú·Î¿Ùˆ, ÂËÚ¤·Û·Ó ÛËÌ·ÓÙÈο ÙȘ ÂȉfiÛÂȘ ÔÏÏÒÓ EÏÏËÓÈÎÒÓ EÈÛÙËÌÔÓÈÎÒÓ ÂÓÙ‡ˆÓ. MÈ· ·Ú¯È΋ ‰È·›ÛÙˆÛË Â›Ó·È fiÙÈ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ‰ÂÓ ˘¿Ú¯Ô˘Ó ϤÔÓ ÛÔ‚·Ú¿ ΛÓËÙÚ· Û ÌÂÁ¿Ï˜ ÂÈÛÙËÌÔÓÈΤ˜ ÔÌ¿‰Â˜ ÁÈ· ¤Ú¢ӷ Î·È ‰ËÌÔÛȇÛÂȘ, fiˆ˜ ÂÍÂÏ›ÍÂȘ ÛÙÔ˘˜ ¯ÒÚÔ˘˜ ÙˆÓ ¶·ÓÂÈÛÙËÌÈ·ÎÒÓ MÂÏÒÓ ¢E¶, ÚÔÎËÚ‡ÍÂȘ Ó¤ˆÓ ı¤ÛˆÓ, ÂÍÂÏ›ÍÂȘ ÛÙÔ ¯ÒÚÔ ÙÔ˘ EıÓÈÎÔ‡ ™˘ÛÙ‹Ì·ÙÔ˜ YÁ›·˜, ¢È‰·ÎÙÔÚÈΤ˜ ¢È·ÙÚÈ‚¤˜, MÔÓÔÁڷʛ˜ Î·È ÁÂÓÈο ·Ó¿ÁÎË ‰ËÌÈÔ˘ÚÁ›·˜ ‚ÈÔÁÚ·ÊÈÎÒÓ ÛËÌÂȈ̿وÓ. ¶·Ú¿ÏÏËÏ· Ë ··›ÙËÛË ÔÏÏÒÓ ·ÓÂÈÛÙËÌÈ·ÎÒÓ ÎÚÈÙÒÓ ÁÈ· ÙËÓ ·Ó¿ÁÎË ‡·Ú͢ ‰ÈÂıÓÒÓ ‰ËÌÔÛȇÛÂˆÓ ÛÙ· ‚ÈÔÁÚ·ÊÈο ÛËÌÂÈÒÌ·Ù· ÙˆÓ ÎÚÈÓfiÌÂÓˆÓ, ÌÂٷΛÓËÛ ÙÔ ÂӉȷʤÚÔÓ ÙˆÓ Û˘ÁÁڷʤˆÓ ÚÔ˜ ͤӷ -΢ڛˆ˜ AÁÁÏfiʈӷ- EÈÛÙËÌÔÓÈο ¤ÓÙ˘·, Ù· ÔÔ›· ‰È·ı¤ÙÔ˘Ó Î¿ÔÈÔ Û˘ÓÙÂÏÂÛÙ‹ ‚·Ú‡ÙËÙ·˜ Î·È ‚Ú›ÛÎÔÓÙ·È Î·È ·Ú¯ÂÈÔıÂÙË̤ӷ Û οÔÈ· Ì˯·Ó‹ HÏÂÎÙÚÔÓÈ΋˜ K·Ù·¯ÒÚËÛ˘ Î·È AÓ·˙‹ÙËÛ˘ . T¤ÏÔ˜ Ë Â› ÙÚÈÂÙ›· ·Ó·ÛÙÔÏ‹ Ù˘ ÂÈÛ‰Ô¯‹˜ Ó¤Ô˘ ¢È‰·ÎÙÈÎÔ‡ ÚÔÛˆÈÎÔ‡ -·ÚÈ· ÂÈÛ·ÁˆÁÈÎÒÓ ‚·ıÌ›‰ˆÓ- ÛÙÔ˘˜ ¯ÒÚÔ˘˜ ÙˆÓ AEI, ¤¯ÂÈ Ï¤ÔÓ ‰ËÌÈÔ˘ÚÁ‹ÛÂÈ Î·ıÂÛÙÒ˜ ·‰È·ÊÔÚ›·˜ Î·È ·ÚÓËÙÈÛÌÔ‡ ÛÙËÓ ·Ú·ÁˆÁ‹ ÁÚ·ÙÔ‡ ÂÈÛÙËÌÔÓÈÎÔ‡ ÏfiÁÔ˘ ·fi Ó¤Ô˘˜ Î·È ·ÍÈfiÏÔÁÔ˘˜ ÂÈÛÙ‹ÌÔÓ˜, ÂÓÒ ·ÓÙ›ıÂÙ· ·ÓıÔ‡Ó Û ‚·ıÌfi Ì¿ÏÈÛÙ· ÏËıˆÚÈÎfi ÔÈ ·ÚÔ˘ÛÈ¿ÛÂȘ Û ™˘Ó¤‰ÚÈ·, ™˘ÌfiÛÈ·, HÌÂÚ›‰Â˜, KÏÈÓÈο ºÚÔÓÙÈÛÙ‹ÚÈ·, Ì ¿ÊıÔÓÔ ÂÈÛÙËÌÔÓÈÎfi ˘ÏÈÎfi, Ì ¯·Ú·ÎÙ‹Ú· ÂÊËÚÌÔṲ̂Ó˘ ÁÓÒÛ˘ Î·È ÂÌÂÈÚ›·˜. T· ÂÈÛÙËÌÔÓÈο ÂÚÈÔ‰Èο ¤¯Ô˘Ó ›Û˘ ÏËÁ› ·fi ÙËÓ ¿ÓÙÏËÛË ÏËÚÔÊfiÚËÛ˘ ̤ۈ ÙÔ˘ ‰È·‰ÈÎÙ‡Ô˘,·fi fiÔ˘ Ô Î¿ı ÂÈÛÙ‹ÌÔÓ·˜, ÌÔÚ› Ó· ·ÓÙÏ‹ÛÂÈ ÔÔÙ‰‹ÔÙÂ Û˘ÌÏËڈ̷ÙÈ΋ ÁÓÒÛË -fi¯È fiˆ˜ ¿ÓÙÔÙ ˘„ËÏ‹˜ ÔÈfiÙËÙ·˜ Î·È ·ÍÈÔÈÛÙ›·˜- Ì ¯·ÌËÏfi ‹ ·Ó‡·ÚÎÙÔ ÎÔÛÙÔÏfiÁÈÔ Î·È Ì ÂÚÈÔÚÈṲ̂ÓË ÙËÓ ·Ó¿ÁÎË Ó· Û˘ÁÎÂÎÙÚÒÓÂÈ ¤ÓÙ˘· ÛÙÔ ¯ÒÚÔ Ù˘ ÌÂϤÙ˘ ÙÔ˘, Ô˘ Ï›ÁÔ Î·ÈÚfi ÌÂÙ¿ ÌÂÙ·ÙÚ¤ÔÓÙ·È Û ÌÂÁ¿ÏÔ˘ ‚¿ÚÔ˘˜ Î·È ÙÂÚ¿ÛÙÈÔ˘ fiÁÎÔ˘, ÂÓÔ¯ÏËÙÈ΋ ¯·ÚÙfiÌ·˙·. OÈ ÂÈÛÙËÌÔÓÈÎÔ› ÂΉfiÙ˜, Ú¤ÂÈ Ó· Û˘ÓÂÚÁ·ÛıÔ‡Ó ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Î·È Â›Ï˘ÛË ·˘ÙÔ‡ ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜, ‰ÈfiÙÈ Ë ÁÚ·Ù‹ ÁÓÒÛË Ô˘ ¤¯ÂÈ ˘ÔÛÙ› ÙË ‚¿Û·ÓÔ Ù˘ ÔÏÏ·Ï‹˜ ÎÚ›Û˘ Î·È ÂÂÍÂÚÁ·Û›·˜ ·fi ÔÈΛÏÏÔ˘˜ ÎÚÈÙ¤˜, ·ÔÙÂÏ› ÙËÓ ÏÂfiÓ ·ÍÈfiÈÛÙË ÌÔÚÊ‹ ÏËÚÔÊfiÚËÛ˘ ÁÈ· οı ÂÈÛÙ‹ÌÔÓ·, ÔÈ ‰Â EÏÏËÓÈΤ˜ ¢ËÌÔÛȇÛÂȘ Â›Ó·È Ë ÈÔ Â‡ÂÙË ÔÚÊ‹ ÁÓÒÛ˘ ÁÈ· ÙÔÓ Â˘·ÈÛıËÙÔÔÈË̤ÓÔ E·ÁÁÂÏÌ·Ù›· O‰ÔÓÙ›·ÙÚÔ, Ô˘ ‰ÂÓ ¤¯ÂÈ ÙÔ ¯ÚfiÓÔ Î·È ›Ûˆ˜ Î·È ÙË ‰˘Ó·ÙfiÙËÙ· Ó· ÂÚÈËÁÂ›Ù·È ÛÙȘ HÏÂÎÙÚÔÓÈΤ˜ BÈ‚ÏÈÔı‹Î˜ ÁÈ· Ó· ÂÓËÌÂÚˆı› › ıÂÌ¿ÙˆÓ Ù˘ ηıËÌÂÚÈÓ‹˜ ¿ÛÎËÛ˘ ÙÔ˘ ÏÂÈÙÔ˘ÚÁ‹Ì·Ùfi˜ ÙÔ˘. I. °. TZOYTZA™ ¢È¢ı˘ÓÙ‹˜ ™‡ÓÙ·Í˘ T· EÏÏËÓÈο ™ÙÔÌ·ÙÔÏÔÁÈο XÚÔÓÈο ÛÙÔ ‰È·‰›ÎÙ˘Ô O‰ËÁ›Â˜ ÁÈ· ÙËÓ ·Ó·˙‹ÙËÛ‹ ÙÔ˘˜ 1. 2. 3. 4. 5. 6. ¶ÏËÎÙÚÔÏÔÁ›ÛÙ http://www.eoo.gr – EÈϤͷÙ ÙËÓ ÂÓfiÙËÙ· «EΉfiÛÂȘ» – EÌÊ·Ó›˙ÂÙ·È Ë ÛÂÏ›‰· EÌÊ·Ó›˙ÂÙ·È Ë ÛÂÏ›‰· EÈϤͷÙ ٷ «EÏÏËÓÈο ™ÙÔÌ·ÙÔÏÔÁÈο XÚÔÓÈο». EÈϤͷÙ ÙÔ ¤ÙÔ˜ Ô˘ Û·˜ ÂӉȷʤÚÂÈ EÈϤͷÙ ÙËÓ ÂÚÁ·Û›· Ô˘ Û·˜ ÂӉȷʤÚÂÈ ¢ÒÛÙ ÂÓÙÔÏ‹ ÁÈ· ·Ôı‹Î¢ÛË ‹ ÂÎÙ‡ˆÛË Ù˘ ÂÓfiÙËÙ·˜ Ô˘ Û·˜ ÂӉȷʤÚÂÈ ™˘ÓÙÌ‹ÛÂȘ Î·È ™‡Ì‚ÔÏ· ™Ù·ıÂÚÒÓ MÔÓ¿‰ˆÓ, ™Ù·ÙÈÛÙÈÎÒÓ ŸÚˆÓ Î·È OÚÁ·ÓÔÏÔÁ›·˜ ŸÚÔ˜ ™‡ÓÙÌËÛË ‹ ۇ̂ÔÏÔ ™Ù·ıÂÚ¤˜ ÌÔÓ¿‰Â˜ ampere A angström AÆ barm b calorie cal candela cd coulomb C counts per minute cpm counts per second cps curie Ci degree Celsius ÆC disintegration per minute dpm disintegration per second dps electron Volt eV equivalent Eq farad F gauss G gram g henry H hertz Hz hour h inch in ŸÚÔ˜ international unit joule kelvin kilogram liter/litre meter, metre minute molar mole newton normal (concentration) ohm osmol pascal pound pound per square inch revolutions per minute second square centimeter volt watt week year ™‡ÓÙÌËÛË ‹ ۇ̂ÔÏÔ IU J K kg I or L m min M mol N N ø osmol Pa lb psi rpm s cm2 V W wk yr ™‡ÓÙÌËÛË ‹ ۇ̂ÔÏÔ ŸÚÔ˜ correlation coefficient degrees of freedom mean mean not significant number of observations teragigamegakilohectodecadeciSEM: TEM: ESEM: CSEM: AFM: SPM: EELS: EDS: EPMA: XRF: XRD: FTIR: (1012) (109) (106) (103) (102) (10) (10-1) ™‡ÓÙÌËÛË ‹ ۇ̂ÔÏÔ ŸÚÔ˜ ™Ù·ÙÈÛÙÈÎÔ› fiÚÔÈ probability standard deviation Standard error of the mean Student’s test n variance r df x NS ™˘Ó‰˘·ÛÌfi˜ ÚÔıÂÌ¿ÙˆÓ T centiG miliM microk nanoh picoda femtod atto- (10-2) (10-3) (10-6) (10-9) (10-12) (10-15) (10-18) Scanning Electron Microscopy Transmission Electron Microscopy Environmental Scanning Electron Microscopy Confocal Scanning Electron Microscopy Atomic Force Microscopy Scanning Probe Microscopy Electron Energy Loss Spectrometry Element Dispersive Spectroscopy Electron Probe Microanalysis X-ray Fluorescence analysis X-ray Diffraction Fourrier Transformation Infrared Spectroscopy p SD SE t test F c m Ìm n p f a O¢H°IE™ °IA TOY™ ™Y°°PAºEI™ T· ™TOMATO§O°IKA XPONIKA Â›Ó·È Ë Â›ÛËÌË ÂÈÛÙËÌÔÓÈ΋ ¤Î‰ÔÛË Ù˘ EÏÏËÓÈ΋˜ O‰ÔÓÙÈ·ÙÚÈ΋˜ OÌÔÛÔÓ‰›·˜ Î·È ˆ˜ ÛÙfi¯Ô ¤¯Ô˘Ó ÙË Û˘Ó¯‹ ÂÈÛÙËÌÔÓÈ΋ ÂÓË̤ڈÛË ÙÔ˘ ŒÏÏËÓ· O‰ÔÓÙÈ¿ÙÚÔ˘ Î·È ÙËÓ ÚÔÒıËÛË Ù˘ O‰ÔÓÙÈ·ÙÚÈ΋˜ EÈÛÙ‹Ì˘ ÛÙÔÓ EÏÏËÓÈÎfi ¯ÒÚÔ. °È· ÙËÓ Ú·ÁÌ¿ÙˆÛË ÙÔ˘ ÛÎÔÔ‡ ·˘ÙÔ‡ ‰ËÌÔÛȇÔÓÙ·È: 1. 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ŒÎÙ·ÛË ¿ÚıÚˆÓ: OÈ ·Ó·ÛÎÔ‹ÛÂȘ ‰Â ı· Ú¤ÂÈ Ó· ÍÂÂÚÓÔ‡Ó ÙȘ 7.500 ϤÍÂȘ (25 ‰·ÎÙ˘ÏÔÁÚ·ÊË̤Ó˜ ÛÂÏ›‰Â˜) Î·È ÙȘ 100 ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·Ô̤˜ Ì ÂÍ·›ÚÂÛË ÂȉÈο ı¤Ì·Ù· Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ‚·ÛÈΤ˜ ÂÈÛً̘. OÈ ÂÚ¢ÓËÙÈΤ˜ ÂÚÁ·Û›Â˜ Î·È Ù· Ú·ÎÙÈο ı¤Ì·Ù· ‰Â ı· Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÔ˘Ó ÙȘ 3.000 ϤÍÂȘ (10 ÛÂÏ›‰Â˜) Î·È ÙȘ 40 ·Ú·Ô̤˜. T· ¿ÚıÚ· Ô˘ ·ÊÔÚÔ‡Ó ÂӉȷʤÚÔ˘Û˜ ÂÚÈÙÒÛÂȘ ‰Â ı· Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÔ˘Ó ÙȘ 1.000 ϤÍÂȘ (4 ÛÂÏ›‰Â˜), ÂÓÒ Ù· ·ÁÁÂÏÌ·ÙÈο ı¤Ì·Ù· ı· Ú¤ÂÈ Ó· ÂÚÈÔÚ›˙ÔÓÙ·È ÛÙȘ 5.000 ϤÍÂȘ (20 ÛÂÏ›‰Â˜). ™ÙËÓ ¤ÎÙ·ÛË ÙˆÓ ·Ú·¿Óˆ ¿ÚıÚˆÓ Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÙ·È Î·È Ë ‚È‚ÏÈÔÁÚ·Ê›· Ô˘ ı· Ú¤ÂÈ Ó· Â›Ó·È Â›Î·ÈÚË Î·È Ó· ¤¯ÂÈ ¿ÌÂÛË Û¯¤ÛË Ì ÙÔ ‰È·Ú·ÁÌ·Ù¢fiÌÂÓÔ ı¤Ì·. ™‡ÓÙ·ÍË ÎÂÈ̤ӈÓ: T· ¿ÚıÚ· Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È ÁÈ· ‰ËÌÔÛ›Â˘ÛË Ú¤ÂÈ Ó· Â›Ó·È ÁÚ·Ì̤ӷ ÛÙË ÓÂÔÂÏÏËÓÈ΋ ‰ËÌÔÙÈ΋, Ì ÌÔÓÔÙÔÓÈÎfi Û‡ÛÙËÌ·, ηıÒ˜ ›Û˘ Î·È ÛÙËÓ ·ÁÁÏÈ΋ ÁÏÒÛÛ·. H ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹ ‰È·ÙËÚ› ÙÔ ‰Èη›ˆÌ· Ó· ÂϤÁÍÂÈ ÙËÓ ·ÎÚ›‚ÂÈ· ÙˆÓ ·ÁÁÏfiÊˆÓˆÓ fiÚˆÓ Î·È ‰È·Ù˘ÒÛÂˆÓ ·Â˘ı˘ÓfiÌÂÓË Û ·ÁÁÂÏ̷ٛ˜ È·ÙÚÈÎÔ‡˜ ÌÂÙ·ÊÚ·ÛÙ¤˜. O ‰ÈÔÚıˆÙ‹˜ ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡ ¤¯ÂÈ ÙÔ ‰ÈηÈÒÌ· Ó· ÙÚÔÔÔÈ‹ÛÂÈ ÁψÛÛÈο ÙÔ Î›ÌÂÓÔ, ¯ˆÚ›˜ fï˜ Ó· ·ÏÏÔÈÒÛÂÈ ÙÔ ‡ÊÔ˜ ÙÔ˘ Û˘ÁÁڷʤ·. OÈ ÂÚÁ·Û›Â˜ ·˘Ù¤˜ Ú¤ÂÈ Ó· Â›Ó·È ÏËÎÙÚÔÏÔÁË̤Ó˜ Û ‰ÈÏfi ‰È¿ÛÙËÌ·, Ì ÁÚ·ÌÌ·ÙÔÛÂÈÚ¤˜ Arial, Tahoma ‹ Verdana Ì ÂÚÈıÒÚÈÔ ·fi ÙȘ ‰‡Ô Ï¢ڤ˜. ™Â ȉȷ›ÙÂÚË ÛÂÏ›‰· ·Ú¯›˙Ô˘Ó ÔÈ ÂÍ‹˜ ÂÓfiÙËÙ˜: Ë ÛÂÏ›‰· Ù›ÙÏÔ˘, Ë ÂÚ›ÏË„Ë Î·È ÔÈ Ï¤ÍÂȘ ÎÏÂȉȿ, ÙÔ Î›ÌÂÓÔ Ù˘ ÂÚÁ·Û›·˜, Ë ÂÚ›ÏË„Ë ÛÙËÓ ·ÁÁÏÈ΋ Î·È ÔÈ Ï¤ÍÂȘ ÎÏÂȉȿ ÛÙËÓ ·ÁÁÏÈ΋, ÔÈ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·Ô̤˜, ÔÈ ÏÂ˙¿ÓÙ˜, ÔÈ ›Ó·Î˜ Î·È ÔÈ ÂÈÎfiÓ˜. ŸÏ˜ ÔÈ ÛÂÏ›‰Â˜ ·ÚÈıÌÔ‡ÓÙ·È Ì ÙËÓ ·ÓˆÙ¤Úˆ ÛÂÈÚ¿. ¶ÚÔÎÂÈ̤ÓÔ˘ Ó· ·ÍÈÔÔÈËıÔ‡Ó ÔÈ Â˘ÎÔϛ˜ Ù˘ Û‡Á¯ÚÔÓ˘ Ù¯ÓÔÏÔÁ›·˜ Î·È ÚÔ˜ ·ÔÊ˘Á‹Ó ÙˆÓ ÛÊ·ÏÌ¿ÙˆÓ Î·Ù¿ ÙËÓ ÏËÎÙÚÔÏfiÁËÛË ÎÚ›ÓÂÙ·È Û·Ó ··Ú·›ÙËÙË Ë ˘Ô‚ÔÏ‹ Ù˘ ÂÚÁ·Û›·˜ ÂȘ ÙÚÈÏÔ‡Ó Û˘Óԉ¢fiÌÂÓË ·fi CD fiÔ˘ Ù· ΛÌÂÓ· ı· Ú¤ÂÈ Ó· Â›Ó·È ÏËÎÙÚÔÏÔÁË̤ӷ Û ÚfiÁÚ·ÌÌ· Word Û ¯·Ú·ÎÙ‹Ú˜ 12 ÛÙÈÁÌÒÓ. Afi ÙÔÓ I·ÓÔ˘¿ÚÈÔ ÙÔ˘ 2010 ÔÈ ÂÚÁ·Û›Â˜ ˘Ô‚¿ÏÏÔÓÙ·È Î·È ËÏÂÎÙÚÔÓÈο ÛÙËÓ ‰È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜ ÙˆÓ E™X [email protected] ™ÂÏ›‰· Ù›ÙÏÔ˘: ¶ÂÚÈÏ·Ì‚¿ÓÂÈ: ·) ÙÔÓ Ù›ÙÏÔ Ù˘ ÂÚÁ·Û›·˜, ‚) ÙÔ fiÓÔÌ· Î·È ÙÔÓ Ù›ÙÏÔ ÙÔ˘ (ÙˆÓ) Û˘ÁÁڷʤ· (ˆÓ), Á) ÙÔ ›‰Ú˘Ì· ·’ fiÔ˘ ÚÔ¤Ú¯ÂÙ·È Ë ÂÚÁ·Û›·, ‰) ÙÔ ·Ó Ë ÂÚÁ·Û›· ¤¯ÂÈ ·Ó·ÎÔÈÓˆı› Û οÔÈÔ Û˘Ó¤‰ÚÈÔ Î·È ÔÈÔ, Â) ÙÔ fiÓÔÌ·, ‰È‡ı˘ÓÛË Î·È ÙËϤʈÓÔ ÙÔ˘ Û˘ÁÁڷʤ· ÁÈ· ÙËÓ ·ÏÏËÏÔÁÚ·Ê›·, ÛÙ) ÙÔ ¯·Ú·ÎÙËÚÈÛÙÈÎfi Ù˘ ÂÚÁ·Û›·˜ (‚¿ÛÂÈ ÙÔ˘ 2 ‹ 4), ˙) ¶Èı·Ó‹ ËÁ‹ ¯ÚËÌ·ÙÔ‰fiÙËÛ˘ Ù˘ ¤Ú¢ӷ˜. ¶ÂÚ›ÏË„Ë Î·È Ï¤ÍÂȘ ÎÏÂȉȿ: H ÂÚ›ÏË„Ë ı· Ú¤ÂÈ Ó· ¤¯ÂÈ ¤ÎÙ·ÛË Ì¤¯ÚÈ 200 ϤÍÂȘ. ™ÙȘ ÂÚ¢ÓËÙÈΤ˜ ÂÚÁ·Û›Â˜, Ë ÂÚ›ÏË„Ë ı· Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ ÙÔ ÛÎÔfi ÂÚÁ·Û›·˜, ÙÔ ˘ÏÈÎfi, ÙË ÌÂıÔ‰ÔÏÔÁ›· Î·È Ù· Û˘ÌÂÚ¿ÛÌ·Ù·. OÈ Ï¤ÍÂȘ - ÎÏÂȉȿ ı· ·Ú·Ù›ıÂÓÙ·È Ì ÙËÓ ÂÚ›ÏË„Ë Î·È ı· Ú¤ÂÈ Ó· Â›Ó·È 3-10 ÌÂÌÔӈ̤ÓÔÈ fiÚÔÈ ‹ ÌÈÎÚ¤˜ ÊÚ¿ÛÂȘ. OÈ Ï¤ÍÂȘ ·˘Ù¤˜ ı· Ú¤ÂÈ Ó· ·ÓÙÈÛÙÔÈ¯Ô‡Ó ÛÙÔ˘˜ ‰ÈÂıÓ›˜ fiÚÔ˘˜ ÏÂÍÈÎÔÁÚ¿ÊËÛ˘ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔ Index Medicus Î·È Dental Index Î·È Ó· ÂÌÂÚȤ¯ÔÓÙ·È ÛÙÔ Î›ÌÂÓÔ Ù˘ ÂÚ›Ï˄˘. K›ÌÂÓÔ: T· ¿ÚıÚ· Ô˘ ·ÊÔÚÔ‡Ó ·Ó·ÛÎÔ‹ÛÂȘ ı· Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÔ˘Ó Ì›· ·ÓÙÈÚÔÛˆÂ˘ÙÈ΋ ÂÈÛ·ÁˆÁ‹ Î·È Î·ÙfiÈÓ Ó· ·Ó·Ê¤ÚÔÓÙ·È ÙÂÎÌËÚȈ̤Ó˜ ‚È‚ÏÈÔÁÚ·ÊÈο fiϘ ÔÈ ·fi„ÂȘ Ô˘ ·ÊÔÚÔ‡Ó ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ı¤Ì·. T¤ÏÔ˜, ı· Ú¤ÂÈ Ó· ·Ú·Ù›ıÂÙ·È ÌÈ· ÎÚÈÙÈ΋ ·Ó¿Ï˘ÛË ÙˆÓ ·fi„ÂˆÓ ·˘ÙÒÓ ·fi ÙÔ Û˘ÁÁڷʤ· Î·È Ó· ηٷϋÁÂÈ ÛÂ Û˘ÁÎÂÎÚÈ̤ӷ Û˘ÌÂÚ¿ÛÌ·Ù·. OÈ ÂÚ¢ÓËÙÈΤ˜ ÂÚÁ·Û›Â˜ ı· Ú¤ÂÈ Ó· ·ÔÙÂÏÔ‡ÓÙ·È ·fi Ù· ÎÂÊ¿Ï·È·: EÈÛ·ÁˆÁ‹, YÏÈο Î·È M¤ıÔ‰Ô˜, E˘Ú‹Ì·Ù·-AÔÙÂϤÛÌ·Ù·, ™˘˙‹ÙËÛË Î·È ™˘ÌÂÚ¿ÛÌ·Ù·. ™Ù· ˘fiÏÔÈ· ›‰Ë ÙˆÓ ¿ÚıˆÓ ÙÔ Î›ÌÂÓÔ ‰È·ÌÔÚÊÒÓÂÙ·È Û‡Ìʈӷ Ì ÙȘ ··ÈÙ‹ÛÂȘ ÙÔ˘ ¿ÚıÚÔ˘. BÈ‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·Ô̤˜: OÈ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·Ô̤˜ ÛÙÔ Î›ÌÂÓÔ, fiˆ˜ Î·È ÛÙÔ˘˜ ›Ó·Î˜ Î·È ÛÙȘ ÂÈ- ÎfiÓ˜ Ì ÙȘ ÏÂ˙¿ÓÙ˜ ÙÔ˘˜, ÚÔÛ‰ÈÔÚ›˙ÔÓÙ·È Ì ·Ú·‚ÈÎÔ‡˜ ·ÚÈıÌÔ‡˜ Û ·Ú¤ÓıÂÛË. TÂÏ›˜ ‹ ÎfiÌ·Ù· ÛËÌÂÈÒÓÔÓÙ·È ÌÂÙ¿ ÙËÓ ·Ú¤ÓıÂÛË Ô˘ ·Ú¤¯ÂÈ ÙË ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ú·ÔÌ‹. H ·Ú›ıÌËÛË ÙˆÓ ‚È‚ÏÈÔÁÚ·ÊÈÎÒÓ ·Ú·ÔÌÒÓ Á›ÓÂÙ·È Î·Ù’ ·‡ÍÔÓÙ· ·ÚÈıÌfi Î·È Ì ÙË ÛÂÈÚ¿ Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙÔ Î›ÌÂÓÔ. ŸÏ˜ ÔÈ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·Ô̤˜ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔ Î›ÌÂÓÔ Î·Ù·¯ˆÚÔ‡ÓÙ·È ÛÙÔ ‚È‚ÏÈÔÁÚ·ÊÈÎfi ηٿÏÔÁÔ Ô˘ ·Ú¯›˙ÂÈ Û ȉȷ›ÙÂÚË ÛÂÏ›‰· ÌÂÙ¿ ÙÔ Î›ÌÂÓÔ. ¶ÚÈÓ ·fi οı ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ú·ÔÌ‹ ÛÙÔÓ Î·Ù¿ÏÔÁÔ, ÚÔËÁÂ›Ù·È Ô ·ÓÙ›ÛÙÔȯԘ ·ÚÈıÌfi˜ Ô˘ ÛËÌÂÈÒıËΠÛÙÔ Î›ÌÂÓÔ Î·È ÛÙÔÓ ÔÔ›Ô ·ÓÙÈÛÙÔȯ› Ë ‚È‚ÏÈÔÁÚ·Ê›·. ™ÙÔ ‚È‚ÏÈÔÁÚ·ÊÈÎfi ηٿÏÔÁÔ ÚÔËÁÔ‡ÓÙ·È Ù· ÔÓfiÌ·Ù· ÙˆÓ Û˘ÁÁڷʤˆÓ (ÚÒÙ· ÙÔ ÂÒÓ˘ÌÔ Î·È ÌÂÙ¿ ÙÔ fiÓÔÌ·, ·ÎÔÏÔ˘ı› ÎfiÌ· Î·È ÙÔ ÂÒÓ˘ÌÔ ÙÔ˘ ÂfiÌÂÓÔ˘ Û˘ÁÁڷʤ· Î.Ô.Î.), Ù›ıÂÙ·È ¿Óˆ Î·È Î¿Ùˆ ÛÙÈÁÌ‹ (:) Ô Ù›ÙÏÔ˜ ÙÔ˘ ¿ÚıÚÔ˘, ÙÂÏ›·, ÙÔ ÂÚÈÔ‰ÈÎfi ÛÂ Û˘ÓÙÔÌÔÁÚ·Ê›·, ÙÔ ¤ÙÔ˜, ÙÔ ÚfiÛËÌÔ (;), Ô ÙfiÌÔ˜ ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡, Û ·Ú¤ÓıÂÛË ÙÔ Ù‡¯Ô˜, ¿Óˆ Î·È Î¿Ùˆ ÛÙÈÁÌ‹ Î·È ÔÈ ÛÂÏ›‰Â˜ ÙÔ˘ ¿ÚıÚÔ˘ (ÚÒÙË, ·‡Ï· Î·È ÙÂÏÂ˘Ù·›·). OÈ Û˘ÓÙÌ‹ÛÂȘ ÙˆÓ Ù›ÙÏˆÓ ÂÚÈÔ‰ÈÎÒÓ Ú¤ÂÈ Ó· ÁÚ¿ÊÔÓÙ·È Û‡Ìʈӷ Ì ÙÔ Dental Index Î·È Index Medicus. °È· ÙȘ Û˘ÓÙÌ‹ÛÂȘ ÙˆÓ ÂÏÏËÓÈÎÒÓ ÂÚÈÔ‰ÈÎÒÓ ˘¿Ú¯ÂÈ Û¯ÂÙÈÎfi˜ ηٿÏÔÁÔ˜ ÙÔ˘ IATPOTEK. ¶Ú¤ÂÈ Ó’ ·ÔʇÁÂÙ·È ÁÂÓÈο Ë ¯ÚËÛÈÌÔÔ›ËÛË ÂÚÈÏ‹„ÂˆÓ (abstracts) ˆ˜ ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ú·ÔÌ‹, fiˆ˜ ›Û˘ «·‰ËÌÔÛ›Â˘Ù˜ ·Ú·ÙËÚ‹ÛÂȘ» Î·È «ÚÔÛˆÈΤ˜ ÂÈÎÔÈӈӛ˜». T· «EÏÏËÓÈο ™ÙÔÌ·ÙÔÏÔÁÈο XÚÔÓÈο» Ú¤ÂÈ Ó· Û˘ÓÙÔÌÔÁÚ·ÊÔ‡ÓÙ·È Û·Ó EÏÏ. ™ÙÔÌ. XÚÔÓ. ‹ ·ÁÁÏfiʈӷ Hel Stom Rev. EÚÁ·Û›Â˜ Ô˘ ¤¯Ô˘Ó Á›ÓÂÈ ‰ÂÎÙ¤˜ ÁÈ· ‰ËÌÔÛ›Â˘ÛË, ·ÏÏ¿ ‰Â ‰ËÌÔÛȇıËÎ·Ó ·ÎfiÌË, ÌÔÚÔ‡Ó Ó· ·Ó·ÊÂÚıÔ‡Ó ÛÙË ‚È‚ÏÈÔÁÚ·Ê›·. ™ÙËÓ ÂÚ›ÙˆÛË ·˘Ù‹ ÛËÌÂÈÒÓÂÙ·È ÛÙÔ ÂÚÈÔ‰ÈÎfi Î·È Ë ÊÚ¿ÛË «˘fi ‰ËÌÔÛ›Â˘ÛË» Û ·Ú¤ÓıÂÛË. E¿Ó Î·È ÂÊfiÛÔÓ ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· ÂÌÂÚȤ¯ÔÓÙ·È ¿ÚıÚ· ·fi ÂÚÈÔ‰Èο Ì ϷÙÈÓÔÁÂÓ‹ ÁÏÒÛÛ· Ô˘ ¤¯ÂÈ ÙÔÈΤ˜ ȉȷÈÙÂÚfiÙËÙ˜ (°ÂÚÌ·ÓÈο, ™Î·Ó‰ÈÓ·˘Èο, °·ÏÏÈο), Ô ÙÔÓÈÛÌfi˜ ÙˆÓ Ï¤ÍÂˆÓ Â›Ó·È Â˘ı‡ÓË ÙˆÓ Û˘ÁÁڷʤˆÓ. ¶·Ú¿‰ÂÈÁÌ· ÙÔ˘ ÔÚıÔ‡ ÙÚfiÔ˘ ÁÚ·Ê‹˜ ÙˆÓ ‚È‚ÏÈÔÁÚ·ÊÈÎÒÓ ‰›ÓÂÙ·È ·Ú·Î¿Ùˆ: ¶ÂÚÈÔ‰ÈÎfi: AӷʤÚÔÓÙ·È Ù· ÂÒÓ˘Ì· Î·È Ù· ·Ú¯Èο ÙˆÓ ÔÓÔÌ¿ÙˆÓ fiÏˆÓ ÙˆÓ Û˘ÁÁڷʤˆÓ ̤¯ÚÈ ¤ÍË (fiÙ·Ó Â›Ó·È ÂÚÈÛÛfiÙÂÚÔÈ ·ÎÔÏÔ˘ı› Ë ¤Ó‰ÂÈÍË «et al», ÛÙ· ÂÏÏËÓÈο ¿ÚıÚ· ÁÚ¿ÊÔ˘Ì «Î·È Û˘Ó.»), Ô Ù›ÙÏÔ˜ Ù˘ ÂÚÁ·Û›·˜, Ë Û˘ÓÙÔÌÔÁÚ·Ê›· ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡, ÙÔ ¤ÙÔ˜, Ô ÙfiÌÔ˜, ÙÔ Ù‡¯Ô˜, Ë ÚÒÙË Î·È Ë ÙÂÏÂ˘Ù·›· ÛÂÏ›‰· Ù˘ ‰ËÌÔÛ›Â˘Û˘. ¶.¯. Papagiannoulis L, Kakaboura A, Eliades G: In vivo Vs in Vitro anticariogenic behavior of glass-ionomer and resin composite restorative materials. Dent Mater 2002; 18 (8): 561-569. BÈ‚Ï›· Î·È ¿ÏϘ ÌÔÓÔÁڷʛ˜: AӷʤÚÔÓÙ·È Ì ÙË ÛÂÈÚ¿ Ù· ÂÒÓ˘Ì· Î·È ·Ú¯Èο ÙˆÓ Û˘ÁÁڷʤˆÓ, Ô Ù›ÙÏÔ˜ ÙÔ˘ ‚È‚Ï›Ô˘, Ô ·ÚÈıÌfi˜ ¤Î‰ÔÛ˘, Ë fiÏË ¤Î‰ÔÛ˘. AÎÔÏÔ˘ı› Ô ÂΉfiÙ˘, ÙÔ ¤ÙÔ˜ (¿Óˆ - οو ÙÂÏ›·) ÎÈ Ë ÛÂÏ›‰·. ¶.¯. Ryge GM: Dental Corrosion. 2nd ed. New York. Harper and Row. 1985: 204. AÓ Ë ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ú·ÔÌ‹ ·ÔÙÂÏ› ÎÂÊ¿Ï·ÈÔ ÂÓfi˜ ‚È‚Ï›Ô˘ Ô˘ ¤¯ÂÈ ÁÚ·Ê› ·fi ¿ÏÏÔ Û˘ÁÁڷʤ·, Ë ·Ó·ÊÔÚ¿ Á›ÓÂÙ·È ˆ˜ ÂÍ‹˜: Johnston AJ: Corrosion Resistance of Amalgams. In: Goldman AK, Johns KO, eds. Restorative Materials, Baltimore. Williams and Wilkins Co., 1984-87. IÛÙÔÛÂÏ›‰Â˜: http://www.eudental.org/Community strategy concerning mercury, fiˆ˜ ·˘Ùfi ÂÌÊ·Ó›˙ÂÙ·È ÙËÓ .............. (ËÌÂÚÔÌËÓ›· ·Ó·˙‹ÙËÛ˘). H ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹ ˘ÂÓı˘Ì›˙ÂÈ ÛÙÔ˘˜ Û˘ÁÁÚ·Ê›˜ ÙˆÓ ÂÚÁ·ÛÈÒÓ fiÙÈ Î·Ïfi ›ӷÈ, ÛÙȘ ηٷÙÈı¤ÌÂÓ˜ ÂÚÁ·Û›Â˜ Ó· Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙȘ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·Ô̤˜, ÂÊfiÛÔÓ ‚¤‚·È· ˘Ê›ÛÙ·ÓÙ·È, ÔÈÔÙÈο EÏÏËÓÈο ¿ÚıÚ· Û¯ÂÙÈο Ì ÙÔ ı¤Ì·. AÁÁÏÈ΋ ÂÚ›ÏË„Ë: ¶ÂÚÈÏ·Ì‚¿ÓÂÈ, ÛÙËÓ AÁÁÏÈ΋ ÁÏÒÛÛ·, Ù· ÔÓfiÌ·Ù· ÙˆÓ Û˘ÁÁڷʤˆÓ Î·È ÙÔÓ Ù›ÙÏÔ Ù˘ ÂÚÁ·Û›·˜. ™ÙȘ ·Ó·ÛÎÔ‹ÛÂȘ ı· Ú¤ÂÈ Ó· ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÛÙÔȯ›· ÁÈ· fiÏ· Ù· ÎÂÊ¿Ï·È· Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó Î·È Ù· Û˘ÌÂÚ¿ÛÌ·Ù·. ™ÙȘ ÂÚ¢ÓËÙÈΤ˜ ÂÚÁ·Û›Â˜ ı· Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÂÙ·È Ë ÂÈÛ·ÁˆÁ‹ Ô ÛÎÔfi˜, Ù· ˘ÏÈο Î·È Ë Ì¤ıÔ‰Ô˜, Ù· ·ÔÙÂϤÛÌ·Ù· Ù· Û˘ÌÂÚ¿ÛÌ·Ù· Î·È Ë Û˘˙‹ÙËÛË. H ¤ÎÙ·ÛË ÙˆÓ ÂÚÈÏ‹„ÂˆÓ ı· Ú¤ÂÈ Ó· Î˘Ì·›ÓÂÙ·È ÌÂٷ͇ ÙˆÓ 250 ¤ˆ˜ 350 Ϥ͈Ó. ¶›Ó·Î˜: ¢·ÎÙ˘ÏÔÁÚ·ÊÔ‡ÓÙ·È Û ¯ˆÚÈÛÙ‹ ÛÂÏ›‰· Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ Î·È ÙË ÏÂ˙¿ÓÙ·. H ÏÂ˙¿ÓÙ· Ú¤ÂÈ Ó· Â›Ó·È Û‡ÓÙÔÌË Î·È Î·Ù·ÙÔÈÛÙÈ΋. AÚÈıÌÔ‡ÓÙ·È Ì ·Ú·‚ÈÎÔ‡˜ ·ÚÈıÌÔ‡˜ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔ Î›ÌÂÓÔ. OÈ ÂÂÍËÁ‹ÛÂȘ ÙˆÓ Û˘ÓÙÔÌÔÁÚ·ÊÈÒÓ, ηıÒ˜ Î·È ¿ÏϘ ‰È¢ÎÚÈÓ‹ÛÂȘ, Á›ÓÔÓÙ·È ÛÙÔ Ù¤ÏÔ˜ ÙÔ˘ ›Ó·Î·. EÈÎfiÓ˜: T· Û¯‹Ì·Ù·, Ù· ‰È·ÁÚ¿ÌÌ·Ù· Î·È ÔÈ ÊˆÙÔÁڷʛ˜ Ú¤ÂÈ Ó· ÂÈÛ˘Ó¿ÙÔÓÙ·È ÛÙÔ ÚˆÙfiÙ˘Ô Î·È Ó· Â›Ó·È ˘„ËÏ‹˜ ¢ÎÚ›ÓÂÈ·˜. OÈ ÏÂ˙¿ÓÙ˜ ÙˆÓ ÂÈÎfiÓˆÓ ÁÚ¿ÊÔÓÙ·È Ì ÙÔÓ ·‡ÍÔÓÙ· ·ÚÈıÌfi ÙÔ˘˜ ۠ͯˆÚÈÛÙ‹ ÛÂÏ›‰· ηٿ ÙËÓ ˘Ô‚ÔÏ‹ Ù˘ ÂÚÁ·Û›·˜. Y¿Ú¯ÂÈ ‰˘Ó·ÙfiÙËÙ· ÂÎÙ‡ˆÛ˘ ¤Á¯ÚÒÌˆÓ ÂÈÎfiÓˆÓ ÌÂÙ¿ ·fi Û˘ÓÂÓÓfiËÛË Ì ÙÔ ¢È¢ı˘ÓÙ‹ ™‡ÓÙ·Í˘ Î·È ÙËÓ ËÏÂÎÙÚÔÓÈ΋ ·ÔÛÙÔÏ‹ ÂÁ¯ÚÒÌˆÓ ÊˆÙÔÁÚ·ÊÈÒÓ. OÈ ÂÈÎfiÓ˜ ı· Ú¤ÂÈ Ó· ¤¯Ô˘Ó Û·Úˆı› Ì ·Ó¿Ï˘ÛË ÙÔ˘Ï¿¯ÈÛÙÔÓ 300 dpi, Ó· ¤¯Ô˘Ó ÙË ÌÔÚÊ‹ ·Ú¯Â›ˆÓ JPG Î·È Ó· ÌËÓ ÂÌÂÚȤ¯ÔÓÙ·È ÛÙË ÚÔ‹ ÙÔ˘ ηٷÙÈıÂ̤ÓÔ˘ ÎÂÈ̤ÓÔ˘. EÊfiÛÔÓ ÛÙȘ ÂÈÎfiÓ˜ ÂÌÊ·Ó›˙ÂÙ·È ÙÔ ÚfiÛˆÔ ÙÔ˘ ¿Û¯ÔÓÙÔ˜, Ë ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹, ηٿ ÙË ‰ËÌÔÛ›Â˘ÛË, ı· ηχÙÂÈ ÙËÓ ÂÚÈÔ¯‹ ÙˆÓ ÔÊı·ÏÌÒÓ Ì ̷‡ÚË Ù·ÈÓ›· ÁÈ· ÏfiÁÔ˘˜ Û‚·ÛÌÔ‡ ÚÔÛˆÈÎÒÓ ‰Â‰Ô̤ӈÓ. H ÎÚ›ÛË ÙˆÓ ÂÚÁ·ÛÈÒÓ Á›ÓÂÙ·È ·fi ‰‡Ô ÎÚÈÙ¤˜ Ô˘ ¤¯Ô˘Ó ÂÈÏÂÁ› ·fi ÙËÓ EÈÙÚÔ‹ ™‡ÓÙ·Í˘. H ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹ ÙÔ˘ ¶ÂÚÈÔ‰ÈÎÔ‡ ‰È·ÙËÚ› ÙÔ ‰Èη›ˆÌ· Ó· ÚÔÙ›ÓÂÈ ÙÚÔÔÔÈ‹ÛÂȘ ‹ Ó· ·ÔÚÚ›ÙÂÈ Ù· ¿ÚıÚ· Ô˘ ‰ÂÓ Â›Ó·È ÁÚ·Ì̤ӷ Û‡Ìʈӷ Ì ÙȘ Ô‰ËÁ›Â˜ ÁÈ· ÙÔ˘˜ Û˘ÁÁÚ·Ê›˜. OÈ Û˘ÁÁÚ·Ê›˜ ¤¯Ô˘Ó ÙËÓ ˘Ô¯Ú¤ˆÛË Ì›·˜ Ù˘ÔÁÚ·ÊÈ΋˜ ‰ÈfiÚıˆÛ˘ ̤۷ Û 2 ‚‰ÔÌ¿‰Â˜ ·fi ÙËÓ ·ÔÛÙÔÏ‹ ÙÔ˘ ‰ÔÎÈÌ›Ô˘. MÂÙ¿ ÙËÓ ÛÙËÏÔı¤ÙËÛË ‰Â Á›ÓÔÓÙ·È ‰ÂÎÙ¤˜ ÌÂÙ·‚ÔϤ˜ ÙÔ˘ ÎÂÈ̤ÓÔ˘. T· ‰ËÌÔÛÈÂ˘Ì¤Ó· ¿ÚıÚ·, ÂÈÎfiÓ˜ Î·È ‰È·ÁÚ¿ÌÌ·Ù· ·ÔÙÂÏÔ‡Ó È‰ÈÔÎÙËÛ›· ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡. °È· ÙËÓ ·Ó·‰ËÌÔÛ›Â˘Û‹ ÙÔ˘˜ Â›Ó·È ··Ú·›ÙËÙË Ë ¿‰ÂÈ· Ù˘ ™˘ÓÙ·ÎÙÈ΋˜ EÈÙÚÔ‹˜ Î·È ÙÔ˘ Û˘ÁÁڷʤ·. EÈÛ‹Ì·ÓÛË: °È· ÙËÓ ·Ú·Ï·‚‹ ÂÈÛÙËÌÔÓÈ΋˜ ÂÚÁ·Û›·˜ ÁÈ· ‰ËÌÔÛ›Â˘ÛË Ú¤ÂÈ Ó· ÂÈÛ˘Ó¿ÙÂÙ·È ‰È·‚‚·›ˆÛË ÙˆÓ Û˘ÁÁڷʤˆÓ fiÙÈ Ë ÂÚÁ·Û›· ‰ÂÓ ¤¯ÂÈ Î·Ù·ÙÂı› Û ¿ÏÏÔ ÂÈÛÙËÌÔÓÈÎfi ¤ÓÙ˘Ô ÂÚÈÔ‰ÈÎÔ‡ Ù‡Ô˘, fiÙÈ ‰ÂÓ ÂÚȤ¯ÔÓÙ·È ·˘ÙÔ‡ÛȘ ÚÔÙ¿ÛÂȘ ·fi ¿ÏϘ ÂÈÛÙËÌÔÓÈΤ˜ ‰ËÌÔÛȇÛÂȘ –ÏËÓ ÙˆÓ ÔÚÈÛÌÒÓ, ÓfïÓ, ηÓfiÓˆÓ Î·È ‰È·Ù¿ÍˆӖ Î·È fiÙÈ ÙÔ ÊˆÙÔÁÚ·ÊÈÎfi ˘ÏÈÎfi Â›Ó·È ›‰ÈÔ ‹ ÌÂٷۯ‰›·ÛË ‹ ¿Ïψ˜ Ó· ·Ó·Ê¤ÚÂÙ·È Û·ÊÒ˜ Ë ËÁ‹, ηıÒ˜ ›Û˘ Î·È fiÙÈ ÏËÚÔ‡ÓÙ·È ÔÈ ÚÔ¸Ôı¤ÛÂȘ ÙÔ˘ ¶.¢.39 Ù˘ 1˘ AÚÈÏ›Ô˘ 2009 ·Ú. ºEK 55. INSTRUCTIONS FOR AUTHORS HELLENIC STOMATOLOGICAL REVIEW is the official peer-reviewed open access electronic publication of the Hellenic Dental Association and aims at providing Greek and international dentists with ongoing up-to-date scientific information in all fields of dental science. The Journal publishes the following types of articles: 1. Focus articles: Review articles addressing contemporary and controversial topics proposed by the Editorial Board and written by colleagues with expertise on the particular topics. 2. Original articles: These articles may fall into one of the following categories: (a) Reviews (up to 3 authors), (b) Research papers (Experimental studies, Clinical studies, Laboratory studies, Epidemiological Studies, Clinicostatistical studies, Clinopathological studies), (c) Interesting case reports, (d) Practice-related topics, (e) Scientifically-documented professional issues, (d) Public Health issues, (e) Strategy-related topics, (f) Educational issues and (g) Specific issues. 3. Letters to the Editorial Board: The letters must be approved by the Editorial Board prior to publication and may pertain to: (a) critical reviews of published articles and (b) specific queries on sciencerelated topics, answers to which are provided in the correspondence section. 4. Short reports: These original papers or findings should not exceed 2.000 words and are published as soon as possible after undergoing a review process by the Editorial Board. 5. Reviews from published articles: These reviews focus on Greek colleagues articles recently published in international journals. Article length: Reviews should not exceed 7.500 words (25 typed pages) and should have no more than 100 references, with the exception of special issues related to basic sciences. Research papers and practice-related topics should not exceed 3.000 words (10 pages) and have no more than 40 references. Any articles on important case reports should not exceed 1.000 words (4 pages) while articles addressing professional issues should be no more than 5.000 words (20 pages). The reference list is included in the total word count and must be timely and pertinent to the topic under discussion. Text structure: The manuscripts submitted for publication must be written both in modern Greek, using the monotonic system and in English. The Editorial Board reserves the right to check the accuracy of the English terms and phrasings, consulting with professional medical translators. The Copy Editor of the Journal reserves the right to proceed to linguistic modifications without distorting, though, the authors style. Particularly for the English speaking authors, manuscripts may be submitted only in English language with an extensive (300 words) Greek summary. In this case the scientific editorial board will undertake the preparation of the summary applying the appropriate Greek terminology. All papers submitted must be double spaced, typed in Arial, Tahoma or Verdana font with margins on both sides. The title page, the summary and key words, the main text of the paper, the English summary and key words, the references, the legends, the tables and the figures appear on separate pages. All pages are numbered in the above order. Starting January 2010 all manuscripts are also submitted electronically at [email protected]. Title page: This page includes the following information: (a) title of the paper, (b) name and title of the author(s), (c) institution, (d) whether the paper has been previously presented at a conference and, if yes, details, (e) name, address and telephone of the corresponding author, (f) type of paper (based on 2 or 4), (g) possible source of financing for research. Summary and key words: The summary should be no longer than 200 words. In research papers the summary includes the purpose, the material, the methodology and the conclusions and it is followed by key words which normally include 3-10 key terms or short phrases. The particular words must be in accordance with the international lexicographical terminology as it appears in Index Medicus and Dental Index and must be included in the summary. Main text: Literature reviews should include a comprehensive introduction followed by a summarization of all the views relevant to the topic under discussion, based on specific references. Finally, the author is expected to provide a critical analysis of these views and reach clear conclusions. Research papers should comprise the following chapters: Introduction, Materials and Method, Findings-Results, Discussion and Conclusions. As regards the remaining types of articles, the text should follow an appropriate layout to meet the article demands. References: Any references in the text, the tables and the figure legends are cited by arabic numerals in brackets. Any dots or commas appear after the bracketed reference. The references are numbered consecutively in the order of appearance. All references mentioned in the text are included in the reference list which appears on a separate page after the end of the text. Every reference in the list should be preceded by the number it is identified with in the main text. The reference list should be organised in the following sequence: names of the authors (surname, first name followed by a comma, then surname of the next author and so on), colon (:), title of the article, period (.), abbreviation of the journal, year, semi colon (;),volume, issue in brackets, colon and pages (first page and last page separated by a slash). Titles of Greek journals should be abbreviated in accordance with the IATROTEK list. The use of summaries, unpublished comments or personal communications as references should be avoided. Hellenic Stomatological Review should be abbreviated as Hel Stom Rev. Papers accepted for publication, though not published yet, can be included in the reference list. In this case, the phrase under publication in brackets is added. If the the reference list contains articles from journals using a language of latin origin with language-specific features (German, Scandinavian, French), the authors are responsible for word stress. An example of correct reference presentation is as follows: Journals: The authors surnames and initials appear first (unless there are more than six authors in which case the fifth name is followed by et al), followed by the title of the paper, the journal abbreviation, the year, the volume, the issue and, finally, the first and last page of the publication. E.g. Papagiannoulis L, Kakaboura A, Eliades G: In vivo Vs in Vitro anticariogenic behavior of glassionomer and resin composite restorative materials. Dent Mater 2002; 18 (8): 561-569. Books and other monographs: The authors surnames and initials appear first followed by the title of the book, the number of publication and the city of publication. Next comes the publisher, the year (colon) and the page. E.g. Ryge GM: Dental Corrosion. 2nd ed. New York. Harper and Row. 1985: 204. If the reference corresponds to a chapter from a book written by another author, it should appear as follows: Johnston AJ: Corrosion Resistance of Amalgams. In: Goldman AK, Johns KO, eds. Restorative Materials, Baltimore. Williams and Wilkins Co., 1984-87. Websites: E.g. http://www.eudental.org/Community strategy concerning mercury, as it appears in (search date). The Editoral Board strongly encourages the authors to include references to high quality Greek articles related to the topic under discussion, if possible. English summary: It includes the names of the authors and the title of the paper in English. In literature reviews the summary should present data on all the chapters it includes as well as the conclusions. In research papers the summary includes the introduction, the aim, the materials and methods, the results, the conclusions and the discussion. A summary should be 250 to 300 words long. Tables: They are typed on a separate page including the legend. The legend should be concise and comprehensive. The tables are numbered with Arabic numerals which are also used for citation in the text. Any explanations of the abbreviations or other clarifications appear at the end of the table. Illustrative material: Any figures, diagrams and photographs should be attached to the manuscript and be high-resolution files. Figure legends are numbered consecutively on a separate page during the submission process of the paper. Colour images are possible to print. Authors should contact the Editor-in-Chief and send the colour images electronically. The images should be scanned at a minimum resolution of 300 dpi, in JPG format and should not be included in the main document submitted for publication. In case a patients face is visible in the image the Editorial Board anonymises it, prior to publication, through a black band across the eyes to protect patient confidentiality. The review process is assigned to two reviewers selected by the Editorial Board. The Editorial Board of the Journal reserves the right to suggest revisions or reject articles which have failed to comply with the instructions for authors. It is the authors responsibility to check for typographical errors within 2 weeks from the submission date of the manuscript. After the paper has been formatted in columns no modifications are accepted. Copyrights to all published articles, images and diagrams are assigned to the Journal. Permission by the Editorial Board and the author(s) is necessary prior to any republication. Note: Any paper submitted for publication must be accompanied by a written statement by the author(s) certifying that the paper has not been submitted to any other scientific journal, does not contain unchanged sentences from other scientific publications excluding definitions, laws, rules and regulations and that the illustrative material is the same as the original or a redesign, otherwise the source must be clearly stated. EÚ¢ÓËÙÈ΋ EÚÁ·Û›· Research Study ÕÛÎÔË ÔÏ˘Ê·Ú̷Λ· ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÓÔÛËÌ¿ÙˆÓ ÙÔ˘ ÛÙfiÌ·ÙÔ˜. AÓ·‰ÚÔÌÈ΋ ÌÂϤÙË Û 458 ·ÛıÂÓ›˜. E. M. K·ÏÔÁ‹ÚÔ˘*, K. I. TfiÛÈÔ˜**, A. ™ÎÏ·‚Ô‡ÓÔ˘*** Drug abuse in the management of oral diseases. Retrospective study in 458 patients. E.M. Kalogirou*, K.I. Tosios**, A. Sklavounou*** ¶EPI§HæH SUMMARY EÈÛ·ÁˆÁ‹: H ¿ÛÎÔË ¯ÔÚ‹ÁËÛË Ê·ÚÌ¿ÎˆÓ ÛÙÔ ¯ÒÚÔ Ù˘ ™ÙÔÌ·ÙÔÏÔÁ›·˜ ÂȂ‚·ÈÒÓÂÙ·È ·fi ‰Â‰Ô̤ӷ ÂÏÏËÓÈÎÒÓ ÌÂÏÂÙÒÓ Ù· ÙÂÏÂ˘Ù·›· 25 ¯ÚfiÓÈ· Ô˘ ηٷ‰ÂÈÎÓ‡Ô˘Ó ˆ˜ Ë Ê·Ú̷΢ÙÈ΋ ηٿ¯ÚËÛË Û˘¯Ó¿ ηı˘ÛÙÂÚ› ÙË ‰È¿ÁÓˆÛË, Ì ‰˘ÛÌÂÓ›˜ Û˘Ó¤ÂȘ ·ÎfiÌ· Î·È ÁÈ· ÙË ˙ˆ‹ ÙˆÓ ·ÛıÂÓÒÓ Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ, ÂÓÒ ÂÈ‚·Ú‡ÓÂÈ ÔÈÎÔÓÔÌÈο ÙÔ˘˜ ›‰ÈÔ˘˜, ·ÏÏ¿ Î·È ÙË ‰ËÌfiÛÈ· ˘Á›·. ™ÎÔfi˜: H ηٷÁÚ·Ê‹ ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ê·Ú̷΢ÙÈ΋˜ ηٿ¯ÚËÛ˘ Û ÓÔÛ‹Ì·Ù· ÙÔ˘ ÛÙfiÌ·ÙÔ˜ Û ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÙÂÛÛ¿ÚˆÓ ÂÙÒÓ Î·È Ë Û‡ÁÎÚÈÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ·˘ÙÒÓ Ì ٷ Â˘Ú‹Ì·Ù· ÚÔËÁÔ‡ÌÂÓˆÓ ÌÂÏÂÙÒÓ. YÏÈÎfi Î·È M¤ıÔ‰Ô˜: 458 Ê¿ÎÂÏÔÈ ·ÛıÂÓÒÓ, ·fi ÙÔ Introduction: The unnecessary dispensing of drugs in Oral Medicine is confirmed by data from Greek research over the past 25 years, which show that drug abuse often delays the diagnosis with adverse effects that burden not only the patients but also the public health system financially. Purpose: To record the cases of drug abuse in oral diseases during a four year period and to compare the results with those of previous studies. Materials and Methods: The records of 458 patients, from a total of 2,662 patients who were referred to the Department of Oral Pathology and Medicine, Dental School, University of Athens during the years 20082011, were retrospectively collected on the basis that * MÂÙ·Ù˘¯È·Î‹ ÊÔÈÙ‹ÙÚÈ· A’ ·ÎÏÔ˘ ** E›ÎÔ˘ÚÔ˜ K·ıËÁËÙ‹˜ *** K·ıËÁ‹ÙÚÈ· * Graduate student ** Assistant Professor *** Professor EÚÁ·ÛÙ‹ÚÈÔ ™ÙÔÌ·ÙÔÏÔÁ›·˜, O‰ÔÓÙÈ·ÙÚÈ΋ ™¯ÔÏ‹, EıÓÈÎfi Î·È K·Ô‰ÈÛÙÚÈ·Îfi ¶·ÓÂÈÛÙ‹ÌÈÔ AıËÓÒÓ. Department of Oral Pathology and Medicine, Dental School, University of Athens. M¤ÚÔ˜ ·˘Ù‹˜ Ù˘ ÂÚÁ·Û›·˜ ¤¯ÂÈ ·Ó·ÎÔÈÓˆı› ÛÙËÓ 1Ë HÌÂÚ›‰· ÙÔ˘ O‰ÔÓÙÈ·ÙÚÈÎÔ‡ ™˘ÏÏfiÁÔ˘ AÙÙÈ΋˜ (26/01/2013), Ì ı¤Ì· «º¿Ú̷η ÛÙËÓ O‰ÔÓÙÈ·ÙÚÈ΋. EӉ›ÍÂȘ, ·ÓÙÂӉ›ÍÂȘ Î·È ·ÓÂÈı‡ÌËÙ˜ ÚÔÂÎÙ¿ÛÂȘ». This study was partly presented at the 1st seminar of Attica Dental Association (26/01/2013): Drugs in dentistry. Indications, contraindications and adverse side effects. ÂÏÏËÓÈο ÛÙÔÌ·ÙÔÏÔÁÈο ¯ÚÔÓÈο 57: 9-17, 2013 ·ÚÂÏ‹ÊıË 28/6/2013 - ÂÎÚ›ıË 26/9/2013 Hellenic Stomatological Review 57: 9-17, 2013 paper received 28/6/2013 - accepted 26/9/2013 9 EÚ¢ÓËÙÈ΋ EÚÁ·Û›· Research Study Û‡ÓÔÏÔ 2662 ·ÛıÂÓÒÓ Ô˘ ÚÔÛ‹Ïı·Ó ÛÙËÓ KÏÈÓÈ΋ Ù˘ ™ÙÔÌ·ÙÔÏÔÁ›·˜ Ù˘ O‰ÔÓÙÈ·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ AıËÓÒÓ Î·Ù¿ Ù· ¤ÙË 2008-2011, ÂÈϤ¯ıËÎ·Ó ·Ó·‰ÚÔÌÈο Ì ÎÚÈÙ‹ÚÈÔ fiÙÈ ÛÙËÓ ·ÚÔ‡Û· ÓfiÛÔ ·Ó·ÊÂÚfiÙ·Ó Ï‹„Ë Ê·ÚÌ¿ÎÔ˘ ‹ Ê·ÚÌ¿ÎˆÓ ÁÈ· ÙË ıÂڷ›· ÙÔ˘ ÛÙÔÌ·ÙÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÚÈÓ ÙËÓ ÚÔÛ¤ÏÂ˘Û‹ ÙˆÓ ·ÛıÂÓÒÓ ÛÙËÓ KÏÈÓÈ΋. AÔÙÂϤÛÌ·Ù·: ÕÛÎÔË Ï‹„Ë Ê·ÚÌ¿ÎˆÓ ÚÈÓ ÙËÓ ÙÂÎÌËÚ›ˆÛË Ù˘ ÙÂÏÈ΋˜ ‰È¿ÁÓˆÛ˘ ÛËÌÂÈÒıËΠÛÙÔ 77% ÙˆÓ ·ÛıÂÓÒÓ, ÌÂ Û˘¯ÓfiÙÂÚË Î·ÙËÁÔÚ›· Ù· ·ÓÙÈÛËÙÈο. TËÓ Â˘ı‡ÓË ·‰ÈηÈÔÏfiÁËÙ˘ Û˘ÓÙ·ÁÔÁÚ¿ÊËÛ˘ ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ¤ÊÂÚ·Ó ÔÈ ˆÙÔÚÚÈÓÔÏ·Ú˘ÁÁÔÏfiÁÔÈ. ™˘˙‹ÙËÛË Î·È Û˘ÌÂÚ¿ÛÌ·Ù·: H Ê·Ú̷΢ÙÈ΋ ηٿ¯ÚËÛË ÛÙÔ ¯ÒÚÔ Ù˘ ™ÙÔÌ·ÙÔÏÔÁ›·˜ ‰ÂÓ ÂÌÊ·Ó›˙ÂÈ Ù¿ÛË Ì›ˆÛ˘ Ì ÙËÓ ¿ÚÔ‰Ô ÙˆÓ ÂÙÒÓ. TÔ ÁÂÁÔÓfi˜ ·˘Ùfi ÂÈ‚¿ÏÏÂÈ ÙËÓ Â·ÁÚ‡ÓËÛË ÙÔ˘ Ô‰ÔÓÙÈ·ÙÚÈÎÔ‡ Î·È È·ÙÚÈÎÔ‡ ÎfiÛÌÔ˘, ÒÛÙÂ Ë ıÂڷ›· Ó· ¤ÂÙ·È Ù˘ ‰È¿ÁÓˆÛ˘ Î·È ÔÈ ·ÛıÂÓ›˜ Ó· ÌËÓ ÂÈ‚·Ú‡ÓÔÓÙ·È ·fi ÙȘ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ÙˆÓ Ê·Ú̿ΈÓ. §¤ÍÂȘ ÎÏÂȉȿ: ηٿ¯ÚËÛË Ê·Ú̿ΈÓ, ÓÔÛ‹Ì·Ù· ÛÙfiÌ·ÙÔ˜, ·‰ÈηÈÔÏfiÁËÙË Û˘ÓÙ·ÁÔÁÚ¿ÊËÛË. EI™A°ø°H «K·Ù¿¯ÚËÛË», «Ï·Óı·Ṳ̂ÓË», «¿ÎÚÈÙË Î·È ·ÏfiÁÈÛÙË» ‹ «ÌË-È·ÙÚÈ΋» ¯Ú‹ÛË Ê·Ú̿ΈÓ, «·‰ÈηÈÔÏfiÁËÙË Û˘ÓÙ·ÁÔÁÚ¿ÊËÛË» Î·È «¿ÛÎÔË ÔÏ˘Ê·Ú̷Λ·» Â›Ó·È fiÚÔÈ Ô˘ ·ÓÙ·Ó·ÎÏÔ‡Ó ÙËÓ ·ÓËÛ˘¯›· Ù˘ È·ÙÚÈ΋˜ ÎÔÈÓfiÙËÙ·˜ ÁÈ· ÙË Û˘Ó¯Ҙ ·˘Í·ÓfiÌÂÓË Ù¿ÛË ¯Ú‹Û˘ Ê·Ú̷΢ÙÈÎÒÓ Û΢·ÛÌ¿ÙˆÓ ¯ˆÚ›˜ ¤Ó‰ÂÈÍË. TËÓ ·ÓËÛ˘¯›· ·˘Ù‹ ÂÈÙ›ÓÔ˘Ó ÂȉËÌÈÔÏÔÁÈο ÛÙÔȯ›· ·fi ÙȘ H¶A, fiÔ˘ ÙÔ 2010 ÁÈÓfiÙ·Ó Î·Ù¿¯ÚËÛË Ê·ÚÌ¿ÎˆÓ ·fi 7.000.000 Ôϛ٘ οı ̋ӷ, ·ÚÈıÌfi˜ Ô˘ ͤڷÛ ·ÎfiÌ· Î·È ÙÔ˘˜ ¯Ú‹ÛÙ˜ Ó·ÚΈÙÈÎÒÓ Î·È ·Ú·ÈÛıËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ1. EÈϤÔÓ, ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ·Ó Î·È Ô ·ÚÈıÌfi˜ ÙˆÓ ÂÈÛΤ„ÂˆÓ ÛÙ· ÙÌ‹Ì·Ù· ÂÂÈÁfiÓÙˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ ·Ú·Ì¤ÓÂÈ ÛÙ·ıÂÚfi˜, ÙÔ ÔÛÔÛÙfi Ô˘ ÔÊ›ÏÂÙ·È Û ÂÈÏÔΤ˜ ·fi Ï·Óı·Ṳ̂ÓË Ï‹„Ë Ê·ÚÌ¿ÎˆÓ ·˘Í‹ıËΠηٿ 44%1. H Ê·Ú̷΢ÙÈ΋ ηٿ¯ÚËÛË ·ÊÂÓfi˜ ÂÈ‚·Ú‡ÓÂÈ ÙËÓ ˘Á›· ÙˆÓ ·ÛıÂÓÒÓ, ›Ù ÏfiÁˆ ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÙˆÓ ·ÚÂÓÂÚÁÂÈÒÓ Î·È Ù˘ Ù˘¯fiÓ Û˘Ó¤ÚÁÂÈ·˜ ÙˆÓ Ê·Ú̷΢ÙÈÎÒÓ Û΢·ÛÌ¿ÙˆÓ, ηıÒ˜ Î·È ÙÔ˘ ÁÂÁÔÓfiÙÔ˜ fiÙÈ Î·ı˘ÛÙÂÚ› Ë ‰È¿ÁÓˆÛË ÙÔ˘ ÛÙÔÌ·ÙÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜, Î·È ·ÊÂÙ¤ÚÔ˘ Ô‰ËÁ› ÛÙËÓ ÔÈÎÔÓÔÌÈ΋ ÂÈ‚¿Ú˘ÓÛË ·ÛıÂÓÒÓ Î·È ‰ËÌÔÛ›ˆÓ Ù·Ì›ˆÓ. H ηٿ¯ÚËÛË ÙˆÓ Ê·ÚÌ¿ÎˆÓ ‰ÂÓ ·Ê‹ÓÂÈ ·ÓÂËÚ¤·ÛÙË ÙËÓ Ô‰ÔÓÙÈ·ÙÚÈ΋ ÎÔÈÓfiÙËÙ·. Œ¯ÂÈ ˘ÔÏÔÁÈÛÙ› fiÙÈ ÂÚÈÛÛfiÙÂÚÔ ·fi ÙÔ 40% ÙˆÓ Ô‰ÔÓÙÈ·ÙÚÈÎÒÓ ·ÛıÂÓÒÓ Ô˘ Ï·Ì‚¿ÓÔ˘Ó Ê¿Ú̷η ÂÈ‚·Ú‡ÓÂÙ·È ·fi ÙȘ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȤ˜ ÙÔ˘˜, ÔÛÔÛÙfi Ô˘ ·˘Í¿ÓÂÙ·È Î·Ù¿ Ôχ Û ÂÚÈÙÒÛÂȘ fiÔ˘ Ë Ï‹„Ë ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ‰ÂÓ Á›ÓÂÙ·È 10 the patients had already taken medications for the treatment of their oral disease before attending the clinic. Results: Unnecessary drug abuse before the documentation of the final diagnosis was recorded in 77% of the patients and antiseptics were the drugs most commonly overused. ENT specialists more frequently bore the responsibility for irrational drug prescription. Discussion and conclusions: No decline in the rate of drug abuse in Oral Medicine is observed over the years. Awareness of both the dental and medical community is required so that treatment follows accurate diagnosis and patients are free of the medications’ side effects. Key Words: drug abuse, oral diseases, irrational prescription. INTRODUCTION “Abuse”, “misuse”, “overuse”, “non medical use” of drugs or “irrational drug prescription” and “unreasonable polypharmacy” are synonymous terms reflecting the medical community’s concern about the increasing tendency for drug use without any indication; a concern that is raised because of epidemiological data from the U.S.A., where in 2010 medication abuse occurs among 7,000,000 people every month, a number which surpasses the users of cocaine, heroin or hallucinogens1. Although the number of drug-related visits in the Emergency Departments remained stable during the recent years, a 44% increase in drug overuse-related visits to the Emergency Departments was recorded1. Drug abuse not only affects patients’ health, because of medications’ side effects or synergy or even a delay in the diagnosis of their oral disease, but also affects both the patients and the public health system financially. Dentistry could not be unaffected by medications’ abuse. It has been estimated that more than 40% of dental patients taking drugs suffer from the medications adverse reactions, a percentage that increases significantly in cases of non medical drug use2. It is also reported that 5% of visits to the Greek Hospitals are estimated to have occured as a result of medications’ side effects, while that ratio among the elderly approximates even 20%2. A wide variety of drugs are used in the management of oral diseases, including antiseptics, analgesics-antipyretics, non steroidal anti-inflammatory drugs, antibiotics, antivirals, antifungals and corticosteroids (topical or systemic), drugs for the central nervous system, antihistamines, healing drugs, immunosuppressive-immunomodulatory drugs, antineoplastic drugs and saliva substitutes for the treatment of xerostomia. Drug abuse has been presented in three previous Greek studies, all conducted at the Department of Oral Pathology and Hellenic Stomatological Review 57: 9-17, 2013 EÚ¢ÓËÙÈ΋ EÚÁ·Û›· Research Study ÌÂÙ¿ ·fi È·ÙÚÈ΋ Ô‰ËÁ›·2. AӷʤÚÂÙ·È, ›Û˘, ˆ˜ ÙÔ 5% ÙˆÓ ÂÈÛ·ÁˆÁÒÓ ÛÙ· ÓÔÛÔÎÔÌ›· ÛÙËÓ EÏÏ¿‰· ÔÊ›ÏÂÙ·È Û ·ÚÂÓ¤ÚÁÂȘ Ê·Ú̿ΈÓ, ÔÛÔÛÙfi Ô˘ ÚÔÛÂÁÁ›˙ÂÈ Ì¤¯ÚÈ Î·È ÙÔ 20% ÛÙËÓ ÙÚ›ÙË ËÏÈΛ·2. °È· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ·ı‹ÛÂˆÓ Ù˘ ÛÙÔÌ·ÙÈ΋˜ ÎÔÈÏfiÙËÙ·˜ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ‰È¿ÊÔÚ˜ ηÙËÁÔڛ˜ Ê·Ú̿ΈÓ, ΢ڛˆ˜ ·ÓÙÈÛËÙÈο, ·Ó·ÏÁËÙÈο-·ÓÙÈ˘ÚÂÙÈο, ÌËÛÙÂÚÔÂȉ‹ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë, ·ÓÙÈ‚ÈÔÙÈο, ·ÓÙÈÈο, ·ÓÙÈÌ˘ÎËÙÈ·ÛÈο Î·È ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ (ÙÔÈο ‹ Û˘ÛÙËÌ·ÙÈο), Ê¿Ú̷η ÁÈ· ÙȘ ·ı‹ÛÂȘ ÙÔ˘ ÎÂÓÙÚÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ·ÓÙÈÈÛÙ·ÌÈÓÈο, ÂÔ˘ÏˆÙÈο, ·ÓÔÛÔηٷÛÙ·ÏÙÈο-·ÓÔÛÔÙÚÔÔÔÈËÙÈο, ·ÓÙÈÓÂÔÏ·ÛÌ·ÙÈο Î·È ˘ÔηٿÛٷٷ Û¿ÏÈÔ˘ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÍËÚÔÛÙÔÌ›·˜. H ηٿ¯ÚËÛË Ê·ÚÌ¿ÎˆÓ ¤¯ÂÈ ·ÔÙ˘ˆı› Û ÙÚÂȘ ÚÔËÁÔ‡ÌÂÓ˜ ÌÂϤÙ˜ ·fi ÙÔÓ ÂÏÏËÓÈÎfi ¯ÒÚÔ, fiϘ ·fi ÙËÓ KÏÈÓÈ΋ Ù˘ ™ÙÔÌ·ÙÔÏÔÁ›·˜ Ù˘ O‰ÔÓÙÈ·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ÙÔ˘ EıÓÈÎÔ‡ Î·È K·Ô‰ÈÛÙÚÈ·ÎÔ‡ ¶·ÓÂÈÛÙËÌ›Ô˘ AıËÓÒÓ, ÙfiÛÔ ÁÈ· Û˘ÁÎÂÎÚÈ̤Ó˜ ηÙËÁÔڛ˜ Ê·Ú̿ΈÓ, fiˆ˜ Ù· ·ÓÙÈÛËÙÈο3 Î·È Ù· ·ÓÙÈÌ˘ÎËÙÈ·ÛÈο4, fiÛÔ Î·È ÛÙÔ Û‡ÓÔÏfi ÙÔ˘˜2. ™ÙËÓ ÂÚÁ·Û›· Ù˘ M·˙ÔÔ‡ÏÔ˘3 ÙÔ 1987 ·ÚÔ˘ÛÈ¿ÛÙËÎÂ Ë ¯Ú‹ÛË Î·È Ë Î·Ù¿¯ÚËÛË ÙÔÈÎÒÓ ·ÓÙÈÛËÙÈÎÒÓ ·fi 100 ·ÛıÂÓ›˜ ÛÂ Û˘ÓÔÏÈÎfi ‰Â›ÁÌ· ÂÚ›Ô˘ 1000 ·ÛıÂÓÒÓ. ™ÙË ÌÂϤÙË ÙˆÓ ™ÎÏ·‚Ô‡ÓÔ˘ Î·È ¢Ú›ÎÔ˘4 ÙÔ 1989 ηٷÁÚ¿ÊËÎ·Ó 80 ÂÚÈÙÒÛÂȘ ·ÛıÂÓÒÓ ·fi Û˘ÓÔÏÈÎfi ‰Â›ÁÌ· ÂÚ›Ô˘ 1000 ·ÛıÂÓÒÓ, ÔÈ ÔÔ›ÔÈ ÚÈÓ ·fi ÙËÓ ÚÔÛ¤ÏÂ˘Û‹ ÙÔ˘˜ ÛÙËÓ KÏÈÓÈ΋ Ù˘ ™ÙÔÌ·ÙÔÏÔÁ›·˜ ›¯·Ó οÓÂÈ ¯Ú‹ÛË ·ÓÙÈÌ˘ÎËÙÈ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÌÂÙ¿ ·fi ·Ú·›ÓÂÛË Ô‰ÔÓÙÈ¿ÙÚÔ˘ ‹ È·ÙÚÔ‡, ‹ Ì ‰È΋ ÙÔ˘˜ ÚˆÙÔ‚Ô˘Ï›·. ™ÙËÓ ÈÔ ÚfiÛÊ·ÙË ¤Ú¢ӷ ÙˆÓ X·Ù˙ËÁÈ¿ÓÓË Î·È Û˘Ó.2 ÙÔ 2007 Û˘ÁÎÂÓÙÚÒıËÎ·Ó 217 ÂÚÈÙÒÛÂȘ ·ÛıÂÓÒÓ ·fi Û‡ÓÔÏÔ ÂÚ›Ô˘ 1000, ÔÈ ÔÔ›ÔÈ Â›¯·Ó οÓÂÈ ¯Ú‹ÛË Î¿ÔÈÔ˘ Ê·ÚÌ¿ÎÔ˘, ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ·ÓÙÈ‚ÈÔÙÈÎÔ‡, ·ÓÙÈÛËÙÈÎÔ‡ ‹ ·ÓÙÈÌ˘ÎËÙÈ·ÛÈÎÔ‡, ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ÛÙÔÌ·ÙÈÎÔ‡ ÙÔ˘˜ ÓÔÛ‹Ì·ÙÔ˜. H ·ÏfiÁÈÛÙË ¯Ú‹ÛË Ê·ÚÌ¿ÎˆÓ ·fi ÙÔ˘˜ ÛÙÔÌ·ÙÔÏÔÁÈÎÔ‡˜ ·ÛıÂÓ›˜ ÔÊ›ÏÂÙ·È ¿ÏÏÔÙ ÛÙËÓ ·‰ÈηÈÔÏfiÁËÙË Û˘ÓÙ·ÁÔÁÚ¿ÊËÛ‹ ÙÔ˘˜ ·fi ÙÔ˘˜ ıÂÚ¿ÔÓÙ˜ Ô‰ÔÓÙÈ¿ÙÚÔ˘˜ ‹ È·ÙÚÔ‡˜, Î·È ¿ÏÏÔÙ ÛÙËÓ Ï‹„Ë ÙÔ˘˜ ÌÂÙ¿ ·fi Û‡ÛÙ·ÛË ÙÔ˘ Ê·ÚÌ·ÎÔÔÈÔ‡ ‹ ÚˆÙÔ‚Ô˘Ï›· ÙˆÓ ›‰ÈˆÓ ÙˆÓ ·ÛıÂÓÒÓ2-4. ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÂÚÁ·Û›·˜ Â›Ó·È Ë ‰ÈÂÚ‡ÓËÛË Ù˘ Èı·Ó‹˜ ·‰ÈηÈÔÏfiÁËÙ˘ ¯Ú‹Û˘ Ê·ÚÌ¿ÎˆÓ ·fi ·ÛıÂÓ›˜ Ì ÛÙÔÌ·ÙÔÏÔÁÈο ÓÔÛ‹Ì·Ù·, fiˆ˜ ‰È·ÌÔÚÊÒıËΠηٿ Ù· ¤ÙË 2008-2011, Î·È Ë Û‡ÁÎÚÈÛË ÙˆÓ ÛËÌÂÚÈÓÒÓ ‰Â‰ÔÌ¤ÓˆÓ Ì ·˘Ù¿ ÚÔËÁÔ˘Ì¤ÓˆÓ ÌÂÏÂÙÒÓ Ô˘ ¤¯Ô˘Ó ‰ÈÂÍ·¯ı› ÛÙËÓ EÏÏ¿‰·. Medicine of Dental School of the University of Athens, either with absolute regard to specific drug categories such as antiseptics3 and antifungal4, or to all medications for oral diseases2. In 1987, Bazopoulou3 reported the use and misuse of topical antiseptics by 100 patients out of a total sample of 1,000 patients. Sklavounou and Drikos4 in 1989 recorded 80 cases over a total sample of 1,000 patients, who had already used antifungal for their oral disease either with a dental or medical prescription or on their own initiative. In the most recent study, Hatziyannis et al2 in 2007 reported 217 cases over a total sample of 1,000 patients, who had used medications, most commonly antibiotics, antiseptics or antifungal, for the therapy of their oral disease. Drug overuse in Oral Medicine occurs due to either irrational dental or medical prescription, or because of the patients’ initiative or the pharmacist’s recommendation2-4. The purpose of this study is to investigate possible drug abuse among patients with oral diseases during the years 2008-2011 and to compare those results with the relevant data of the previous Greek studies. MATERIALS AND METHODS Of the 2,662 records of patients that were examined at the Department of Oral Pathology and Medicine in Dental School of the University of Athens during the years 20082011, 646 records were retrospectively selected on the basis that the patients had already taken medications for the treatment of their oral disease before attending the clinic. Due to unclear information about either the exact cause of the drug intake or the drug formulation, 52 records were excluded. The remaining 594 records were analyzed with regard to the compatibility of the medication to the final diagnosis. Only the medication class was evaluated, but not the drug substance or the dosage regimen. In 458 out of the 594 (77%) records, there was no compatibility of the medication to the final diagnosis and those patients constituted the “drug abuse” group. Epidemiological data (sex, age), the year of examination and the drug or drugs category were recorded, as well as whether the medication was taken following the patients initiative or a doctor’s recommendation. When there was a prescription, the specialty of the medical professionals was also recorded. RESULTS Y§IKO KAI ME£O¢O™ Afi 2.662 ʷΤÏÔ˘˜ ·ÛıÂÓÒÓ Ô˘ ÂÍÂÙ¿ÛÙËÎ·Ó ÛÙËÓ KÏÈÓÈ΋ Ù˘ ™ÙÔÌ·ÙÔÏÔÁ›·˜ Ù˘ O‰ÔÓÙÈ·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ÙÔ˘ EıÓÈÎÔ‡ Î·È K·Ô‰ÈÛÙÚÈ·ÎÔ‡ ¶·ÓÂÈÛÙËÌ›Ô˘ AıËÓÒÓ ·fi ÙÔÓ I·ÓÔ˘¿ÚÈÔ ÙÔ˘ 2008 ¤ˆ˜ Î·È ÙÔ ¢ÂΤ̂ÚÈÔ ÙÔ˘ 2011, ÂÈϤ¯ıËÎ·Ó ·Ó·‰ÚÔÌÈο 646 Ê¿ÎÂÏÔÈ, ÛÙÔ˘˜ ÔÔ›Ô˘˜ ·Ó·ÊÂÚfiÙ·Ó Ï‹„Ë Ê·ÚÌ¿ÎÔ˘ ‹ Ê·ÚÌ¿ÎˆÓ ÁÈ· ÙÔ ÓfiÛËÌ· Ô˘ ·ÔÙÂÏÔ‡Û ÙËÓ ·ÈÙ›· ÚÔÛ¤ÏÂ˘Û‹˜. Afi ÙÔ˘˜ ʷΤÏÔ˘˜ ·˘ÙÔ‡˜ ÂÍ·ÈÚ¤ıËÎ·Ó 52, ÂÍ·ÈÙ›·˜ ·Û·Hellenic Stomatological Review 57: 9-17, 2013 As far as the patients’ gender is concerned, there were 267 females and 191 males with a female to male ratio of 1.4:1. The age range was from 2.5 to 95 years, the mean age was 50.62 (±19) years, while almost half of the patients (204/458, 44,5%) were between their 50th and 70th year. 5% of the patients were under 18 years old. 66% of the patients (301/458) had taken only one kind of medication, while 2-5 different drug categories (polypharmacy) were taken by 34% (157/458) of the patients. 11 EÚ¢ÓËÙÈ΋ EÚÁ·Û›· Research Study ÊÒÓ ÏËÚÔÊÔÚÈÒÓ Û¯ÂÙÈο Ì ÙËÓ ·ÎÚÈ‚‹ ·ÈÙ›· Ù˘ ¯Ú‹Û˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ‹ ÙÔ Â›‰Ô˜ ÙÔ˘ Û΢¿ÛÌ·ÙÔ˜. ™ÙÔ˘˜ ˘fiÏÔÈÔ˘˜ 594 ʷΤÏÔ˘˜ ÂÎÙÈÌ‹ıËÎÂ Ë Û˘Ì‚·ÙfiÙËÙ· ÌÂٷ͇ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Ô˘ ›¯Â ÏËÊı› ÚÈÓ ·fi ÙËÓ ÂͤٷÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ Î·È Ù˘ ÙÂÏÈ΋˜ ‰È¿ÁÓˆÛ˘. AÍÈÔÏÔÁ‹ıËΠÌfiÓÔÓ Ë Î·ÙËÁÔÚ›· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Î·È fi¯È Ë Ê·Ú̷΢ÙÈ΋ Ô˘Û›· ‹ ÙÔ ‰ÔÛÔÏÔÁÈÎfi Û¯‹Ì·. ™Â 458 ·fi ÙÔ˘˜ 594 (77%) ʷΤÏÔ˘˜ ‰ÂÓ ÚԤ΢„Â Û˘Ìʈӛ· Î·È ·ÔÙ¤ÏÂÛ·Ó ÙȘ ÂÚÈÙÒÛÂȘ «Ê·Ú̷΢ÙÈ΋˜ ηٿ¯ÚËÛ˘». K·Ù·ÁÚ¿ÊËÎ·Ó Ù· ÂȉËÌÈÔÏÔÁÈο ÛÙÔȯ›· ÙˆÓ ·ÛıÂÓÒÓ (ʇÏÔ, ËÏÈΛ·), ÙÔ ¤ÙÔ˜ ÂͤٷÛ˘, Ë Î·ÙËÁÔÚ›· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ‹ ÙˆÓ Ê·ÚÌ¿ÎˆÓ Ô˘ Ï‹ÊıËηÓ, ÙÔ ·Ó Ï‹ÊıËÎÂ/Ï‹ÊıËÎ·Ó ÌÂÙ¿ ·fi ÚˆÙÔ‚Ô˘Ï›· ÙÔ˘ ·ÛıÂÓÔ‡˜ ‹ ˘fi‰ÂÈÍË È·ÙÚÔ‡, Î·È ÛÙË ‰Â‡ÙÂÚË ÂÚ›ÙˆÛË Ë ÂȉÈÎfiÙËÙ· ÙÔ˘ È·ÙÚÔ‡. 189 (41.3%) of the patients were examined in the first two years of the study and 269 (58.7%) in the latter two. Figure 1 presents the drug categories that were taken by the 458 patients in detail. As shown, of the 680 drug formulations that were taken by all of the 458 patients, there was a clear preference for antiseptics (198/680, 29.1%), antifungals (178/680, 26.2%) and antibiotics (124/680, 18.2%) which were selected as a “solution” in almost 3/4 of the cases (500/680), equally by both genders. In particular, antiseptics represented the most commonly used category and in 57% of cases (113/198) they were chosen as monotherapy, while in the remaining cases, antiseptics were combined with 1-4 other medications, mainly with antibiotics and antifungals. A¶OTE§E™MATA ø˜ ÚÔ˜ ÙÔ Ê‡ÏÔ ÙˆÓ ·ÛıÂÓÒÓ, 267 ‹Ù·Ó Á˘Ó·›Î˜ Î·È 191 ¿Ó‰Ú˜, ·Ó·ÏÔÁ›· 1,4:1. TÔ Â‡ÚÔ˜ ÙˆÓ ËÏÈÎÈÒÓ ‹Ù·Ó 2,5-95 ¤ÙË, Ô Ì¤ÛÔ˜ fiÚÔ˜ ËÏÈΛ·˜ ‹Ù·Ó Ù· 50,62 (±19) ¤ÙË, ÂÓÒ Û¯Â‰fiÓ ÔÈ ÌÈÛÔ› ·ÛıÂÓ›˜ (204/458, 44,5%) ‚Ú›ÛÎÔÓÙ·Ó ÌÂٷ͇ 50Ô˘ Î·È 70Ô˘ ¤ÙÔ˘˜ ËÏÈΛ·˜. TÔ 5% ÙˆÓ ·ÛıÂÓÒÓ ‹Ù·Ó ·Ó‹ÏÈÎÔÈ. TÔ 66% ÙˆÓ ·ÛıÂÓÒÓ (301/458) Ï¿Ì‚·Ó ÌfiÓÔ ¤Ó· ›‰Ô˜ Ê·ÚÌ¿ÎÔ˘ (ÌÔÓÔıÂڷ›·), ÂÓÒ ÛÙÔ 34% (157/458) ÁÈÓfiÙ·Ó Û˘Ó‰˘·ÛÙÈ΋ Ï‹„Ë 2-5 Ê·ÚÌ¿ÎˆÓ ‰È·ÊÔÚÂÙÈÎÒÓ Î·ÙËÁÔÚÈÒÓ (ÔÏ˘Ê·Ú̷Λ·). Afi ÙÔ˘˜ ·ÛıÂÓ›˜ 189 (41,3%) ÂÍÂÙ¿ÛÙËÎ·Ó ÛÙ· ÚÒÙ· ‰‡Ô ¤ÙË Ù˘ ÌÂϤÙ˘ Î·È ÔÈ 269 (58,7%) ÛÙ· ‰‡Ô ÙÂÏÂ˘Ù·›·. ™ÙÔ ‰È¿ÁÚ·ÌÌ· 1 ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ·Ó·Ï˘ÙÈο ÔÈ Î·ÙËÁÔڛ˜ Ê·ÚÌ¿ÎˆÓ Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ·fi ÙÔ˘˜ 458 ·ÛıÂÓ›˜. Ÿˆ˜ Ê·›ÓÂÙ·È, ÌÂٷ͇ ÙˆÓ 680 Û΢·ÛÌ¿ÙˆÓ Ô˘ Ï‹ÊıËÎ·Ó Û˘ÓÔÏÈο ·fi ÙÔ˘˜ 458 ·ÛıÂÓ›˜, Û·Ê‹˜ ‹Ù·Ó Ë ÚÔÙ›ÌËÛË ÁÈ· Ù· ·ÓÙÈÛËÙÈο (198/680, 29,1%), Ù· ·ÓÙÈÌ˘ÎËÙÈ·ÛÈο (178/680, 26,2%) Î·È Ù· ·ÓÙÈ‚ÈÔÙÈο (124/680, 18,2%) Ô˘ ÂÈϤ¯ıËÎ·Ó ˆ˜ «Ï‡ÛË» ۯ‰fiÓ ÛÙ· 3/4 ÙˆÓ ÂÚÈÙÒÛÂˆÓ (500/680), ÂÍ›ÛÔ˘ Î·È ·fi Ù· ‰‡Ô ʇϷ. EȉÈÎfiÙÂÚ·, Ù· ·ÓÙÈÛËÙÈο ·ÓÙÈÚÔÛÒ¢·Ó ÙË Û˘¯ÓfiÙÂÚË ·ÁˆÁ‹, ÛÙÔ 57% (113/198) ˆ˜ ÌÔÓÔıÂÚ·- ¢È¿ÁÚ·ÌÌ· 1: K·ÙËÁÔڛ˜ ÙˆÓ 680 Ê·ÚÌ¿ÎˆÓ Ô˘ ¤Ï·‚·Ó ÔÈ 458 ·ÛıÂÓ›˜. 12 Figure 1: Categories of the 680 drugs of the 458 patients. According to patients’ statements, in 157 cases (34.3%) there was a dental or medical prescription, 21 (4.6%) patients had gone to 2-4 dentists or physicians, 155 (33.8%) patients had taken the medications on their own initiative, while in 125 (27.3%) cases, there were no relevant information. Medications were irrationally prescribed mainly by ENT specialists (178 cases), followed by dentists, “oral pathologists”, dermatologists, physicians and other medical specialists (figure 2). The total ratio of patients who had taken medications on their own initiative (33.8% or 155/458 cases) was equal to the partial percentages for the two genders (33.3% or 89/267 cases among females and 34.6% or 66/191 cases among males). No gender predilection was found in the percentage of patients who considered their oral disease as “dental” and thus went to a general dental practitioner, a dental specialist or an “oral pathologist” (14% or 64/458 cases among all the patients, 14.6% or 39/267 cases among females and 13.1% or 25/191 cases among males). In conclusion, table 1 presents a few representative examples of drug abuse from patients that were examined at the Department of Oral Medicine and Pathology of Dental School during the years 2008-2011. Hellenic Stomatological Review 57: 9-17, 2013 EÚ¢ÓËÙÈ΋ EÚÁ·Û›· Research Study ›·, ÂÓÒ ÛÙȘ ˘fiÏÔȘ ÂÚÈÙÒÛÂȘ Û˘Ó‰˘¿ÛÙËÎ·Ó Ì 1-4 ¿ÏÏ· Ê¿Ú̷η, Ì ·ÚÈÔ˘˜ ÂÎÚÔÛÒÔ˘˜ Ù· ·ÓÙÈ‚ÈÔÙÈο Î·È Ù· ·ÓÙÈÌ˘ÎËÙÈ·ÛÈο. ™‡Ìʈӷ Ì ٷ fiÛ· ·Ó·Ê¤ÚÔÓÙ·Ó ·fi ÙÔ˘˜ ·ÛıÂÓ›˜, Û 157 ÂÚÈÙÒÛÂȘ (34,3%) Ù· Ê¿Ú̷η ›¯·Ó Û˘ÓÙ·ÁÔÁÚ·ÊËı› ·fi Ô‰ÔÓÙÈ¿ÙÚÔ˘˜ ‹ È·ÙÚÔ‡˜, 21 (4,6%) ·Â˘ı‡ÓıËÎ·Ó Û 2-4 Ô‰ÔÓÙÈ¿ÙÚÔ˘˜ ‹ È·ÙÚÔ‡˜, 155 (33,8%) ·ÛıÂÓ›˜ ¤Ï·‚·Ó οÔÈÔ Ê¿ÚÌ·ÎÔ Ì ‰È΋ ÙÔ˘˜ ÚˆÙÔ‚Ô˘Ï›·, ÂÓÒ Û 125 (27,3%) ÂÚÈÙÒÛÂȘ ‰ÂÓ ˘‹Ú¯·Ó ÔÈ Û¯ÂÙÈΤ˜ ÏËÚÔÊÔڛ˜. ÕÛÎÔË ¯ÔÚ‹ÁËÛË Ê·ÚÌ¿ÎˆÓ Û˘ÛÙ‹ıËΠηٿ ·ÚÈÔ ÏfiÁÔ ·fi ÙÔ˘˜ ˆÙÔÚÚÈÓÔÏ·Ú˘ÁÁÔÏfiÁÔ˘˜ (178 ÂÚÈÙÒÛÂȘ) Î·È ·ÎÔÏÔ˘ıÔ‡Û·Ó Ô‰ÔÓÙ›·ÙÚÔÈ, «ÛÙÔÌ·ÙÔÏfiÁÔÈ», ‰ÂÚÌ·ÙÔÏfiÁÔÈ, ·ıÔÏfiÁÔÈ Î·È ¿ÏÏÔÈ (‰È¿ÁÚ·ÌÌ· 2). TÔ Û˘ÓÔÏÈÎfi ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‹Ú·Ó Ì ‰È΋ ÙÔ˘˜ ÚˆÙÔ‚Ô˘Ï›· Ê¿Ú̷η (33,8% ‹ 155/458 ÂÚÈÙÒÛÂȘ) ‹Ù·Ó ·Ú·Ï‹ÛÈÔ Ì ٷ › ̤ÚÔ˘˜ ÔÛÔÛÙ¿ ÁÈ· οı ʇÏÔ (33,3% ‹ 89/267 ÂÚÈÙÒÛÂȘ ÛÙȘ Á˘Ó·›Î˜, Î·È 34,6% ‹ 66/191 ÂÚÈÙÒÛÂȘ ÛÙÔ˘˜ ¿Ó‰Ú˜). ¢ÂÓ ˘‹ÚÍ ‰È·ÊÔÚ¿ ÌÂٷ͇ ÙˆÓ ‰‡Ô Ê‡ÏˆÓ ˆ˜ ÚÔ˜ ÙÔ ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ıÂÒÚËÛ·Ó ÙÔ ÓfiÛËÌ¿ ÙÔ˘˜ «Ô‰ÔÓÙÈ·ÙÚÈÎfi» Î·È ·Â˘ı‡ÓıËÎ·Ó Û οÔÈÔ ÁÂÓÈÎfi ‹ ÂÍÂȉÈÎÂ˘Ì¤ÓÔ Ô‰ÔÓÙ›·ÙÚÔ ‹ Û «ÛÙÔÌ·ÙÔÏfiÁÔ» (14% ‹ 64/458 ÂÚÈÙÒÛÂȘ ÛÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÛıÂÓÒÓ, 14,6% ‹ 39/267 ÂÚÈÙÒÛÂȘ ÛÙȘ Á˘Ó·›Î˜ Î·È 13,1% ‹ 25/191 ÂÚÈÙÒÛÂȘ ÛÙÔ˘˜ ¿Ó‰Ú˜). T¤ÏÔ˜, ÛÙÔÓ ›Ó·Î· 1 ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È, ÂÓ‰ÂÈÎÙÈο, ÔÚÈṲ̂ӷ ·Ú·‰Â›ÁÌ·Ù· ηٿ¯ÚËÛ˘ Ê·ÚÌ¿ÎˆÓ ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÂÍÂÙ¿ÛÙËÎ·Ó ÛÙÔ ‰È¿ÛÙËÌ· 2008-2011 ÛÙËÓ KÏÈÓÈ΋ Ù˘ ™ÙÔÌ·ÙÔÏÔÁ›·˜ Ù˘ O‰ÔÓÙÈ·ÙÚÈ΋˜ ™¯ÔÏ‹˜. ¢È¿ÁÚ·ÌÌ· 2: ¶ÂÚÈÙÒÛÂȘ ¯ÔÚ‹ÁËÛ˘ Ê·ÚÌ¿ÎˆÓ ÌfiÓÔ ·fi Ì›· ÂȉÈÎfiÙËÙ·. ™YZHTH™H H ·ÚÔ‡Û· ·Ó·‰ÚÔÌÈ΋ ÌÂϤÙË Î·Ù¤ÁÚ·„ ÙËÓ Î·Ù¿¯ÚËÛË Ê·ÚÌ¿ÎˆÓ ÁÈ· ÛÙÔÌ·ÙÔÏÔÁÈο ÓÔÛ‹Ì·Ù· ηٿ ÙË ‰È¿ÚÎÂÈ· Ì›·˜ ÙÂÙÚ·ÂÙ›·˜ Û ¤Ó· ÂÍÂȉÈÎÂ˘Ì¤ÓÔ ÛÙÔÌ·ÙÔÏÔÁÈÎfi ΤÓÙÚÔ. T· ·ÔÙÂϤÛÌ·Ù· ‰Â›¯ÓÔ˘Ó ˆ˜ Ë ·ÏfiÁÈÛÙË ¯Ú‹ÛË Ê·ÚÌ¿ÎˆÓ Â›Ó·È Û˘¯Ófi Ê·ÈÓfiÌÂÓÔ Î·È ‰Â ‰È·Ê·›ÓÂÙ·È Ù¿ÛË Ì›ˆÛ˘ Ì ÙËÓ ¿ÚÔ‰Ô ÙˆÓ ÂÙÒÓ. Hellenic Stomatological Review 57: 9-17, 2013 Figure 2: Cases of medication administration by one specialty. DISCUSSION The present retrospective study recorded the drug abuse in oral diseases during a four year period in a center specialized in Oral Medicine and Pathology. The results indicate that irrational drug use is a common phenomenon with no tendency to decrease over the years. Comparing the results of the present study with those of the previous Greek studies, it is obvious that the rates of drug abuse remain constantly high. The irrational use of drugs in this research was estimated at 77% of patients, a higher proportion than in the study of Hatziyannis et al.2 (72%) and Bazopoulou3 (69%), but smaller than that recorded in the study of Sklavounou and Drikos and4 (90%). It should be also noted that the studies of Bazopoulou3 and Sklavounou and Drikos4 referred to the drug abuse of a specific drug category. Furthermore, it seems that antiseptics, antifungals and antibiotics are the most overused drug categories, a finding that is in accordance with the results of the study of Hatziyannis et al.2. Regarding the proportion of drug abuse attributed to the initiative of the patients in the present study, it was estimated at 34% and is almost more than double the 19% in the research of Hatziyannis et al. (19%)2, but less than those of the studies of Sklavounou and Drikos4 (51%) and Bazopoulou3 (57%). It should be noted, however, that as all studies were retrospective, including the present one, and in that of Hatziyannis et al.2 for a large number of patients there was no evidence about who was responsible for the medication administration (27% and 41%, respectively), which might affect the rates. The only encouraging element in the present study was that the percentage of polypharmacy (32%) was lower compared to previous studies, which was 52.5%2, 72.5%4 and 58%3. According to the data of the present study, a great percentage of the irrational prescription was decided by ENT specialists, who alone or in combination with other medical specialties were responsible for drug abuse in 15.3% of cases (70 cases), which is clearly greater than 13 EÚ¢ÓËÙÈ΋ EÚÁ·Û›· Research Study ¶›Ó·Î·˜ 1: ¶·Ú·‰Â›ÁÌ·Ù· ¿ÛÎÔ˘ ÔÏ˘Ê·Ú̷Λ·˜ ·fi ÙËÓ KÏÈÓÈ΋ Ù˘ ™ÙÔÌ·ÙÔÏÔÁ›·˜ ÛÙÔ ‰È¿ÛÙËÌ· 2008-2011. E›‰Ë Ê·ÚÌ¿ÎˆÓ AfiÊ·ÛË ÁÈ· Ù· Ê¿Ú̷η ·ÓÙÈÛËÙÈÎfi, ·ÓÙÈÌ˘ÎËÙÈ·ÛÈÎfi, ·ıÔÏfiÁÔ˜ ·ÓÙÈ‚ÈÔÙÈÎfi, ÙÔÈÎfi TÂÏÈ΋ ‰È¿ÁÓˆÛË ÏÂ˘Îˆfi ›¯ÚÈÛÌ· ÁÏÒÛÛ·˜ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ¤˜ ·ÓÙÈÛËÙÈÎfi, ·ÓÙÈÌ˘ÎËÙÈ·ÛÈÎfi, ¯ˆÚ›˜ ÛÙÔȯ›· ¤ÌÊÈÁ· Ô‰ÔÓÙ›·ÙÚÔ˜ ·Î·ÓıÔ΢ÙÙ·ÚÈÎfi ‚Èٷ̛Ә ·ÓÙÈÛËÙÈÎfi, ·ÓÙÈ‚ÈÔÙÈÎfi ηÚΛӈ̷ Table 1: Examples of irrational polypharmacy from the data of the Department of Oral Medicine and Pathology during the years 2008-2011. Medication type antiseptic, antifungal, antibiotic, Decision for the drug administration general physician topical corticosteroid Final diagnosis white coating on tongue antiseptic, antifungal, vitamins not available pemphigus vulgaris antiseptic, antibiotic dentist squamous cell carcinoma ™˘ÁÎÚ›ÓÔÓÙ·˜ Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ Ì ٷ ·ÓÙ›ÛÙÔȯ· ÙˆÓ ÙÚÈÒÓ ÚÔÁÂÓÂÛÙ¤ÚˆÓ ÌÂÏÂÙÒÓ ·fi ÙËÓ EÏÏ¿‰·, Á›ÓÂÙ·È ÂÌÊ·Ó¤˜ fiÙÈ Ù· ÔÛÔÛÙ¿ Ê·Ú̷΢ÙÈ΋˜ ηٿ¯ÚËÛ˘ ÁÈ· ÛÙÔÌ·ÙÔÏÔÁÈο ÓÔÛ‹Ì·Ù· ·Ú·Ì¤ÓÔ˘Ó ÛÙ·ıÂÚ¿ ˘„ËÏ¿. H ·ÏfiÁÈÛÙË ¯Ú‹ÛË ÙˆÓ Ê·ÚÌ¿ÎˆÓ ÛÙËÓ ·ÚÔ‡Û· ¤Ú¢ӷ ˘ÔÏÔÁ›ÛÙËΠÛÙÔ 77% ÙˆÓ ·ÛıÂÓÒÓ, ÔÛÔÛÙfi ÌÂÁ·Ï‡ÙÂÚÔ ·fi ÙÔ ·ÓÙ›ÛÙÔÈ¯Ô ÛÙȘ ÂÚÁ·Û›Â˜ ÙˆÓ X·Ù˙ËÁÈ¿ÓÓË Î·È Û˘Ó.2 (72%) Î·È Ù˘ M·˙ÔÔ‡ÏÔ˘3 (69%), ·ÏÏ¿ ÌÈÎÚfiÙÂÚÔ ·fi ·˘Ùfi Ô˘ ηٷÁÚ¿ÊËΠÛÙË ÌÂϤÙË ÙˆÓ ™ÎÏ·‚Ô‡ÓÔ˘ Î·È ¢Ú›ÎÔ˘4 (90%). £· Ú¤ÂÈ, ‚¤‚·È·, Ó· ÛËÌÂȈı› fiÙÈ ÔÈ ÌÂϤÙ˜ Ù˘ M·˙ÔÔ‡ÏÔ˘3 Î·È ÙˆÓ ™ÎÏ·‚Ô‡ÓÔ˘ Î·È ¢Ú›ÎÔ˘4 ·ÊÔÚÔ‡Û·Ó Û ηٿ¯ÚËÛË Û˘ÁÎÂÎÚÈ̤Ó˘ ηÙËÁÔÚ›·˜ Ê·Ú̷΢ÙÈÎÒÓ Û΢·ÛÌ¿ÙˆÓ. E›Û˘, Ê·›ÓÂÙ·È ˆ˜ Ù· ·ÓÙÈÛËÙÈο, Ù· ·ÓÙÈÌ˘ÎËÙÈ·ÛÈο Î·È Ù· ·ÓÙÈ‚ÈÔÙÈο Â›Ó·È ÔÈ Î·ÙËÁÔڛ˜ Ê·ÚÌ¿ÎˆÓ Ì ÙË ÌÂÁ·Ï‡ÙÂÚË Î·Ù¿¯ÚËÛË, ‡ÚËÌ· Ô˘ Û˘ÌʈÓ› Ì ٷ ·ÔÙÂϤÛÌ·Ù· Ù˘ ÂÚÁ·Û›·˜ ÙˆÓ X·Ù˙ËÁÈ¿ÓÓË Î·È Û˘Ó.2. AÓ·ÊÔÚÈο Ì ÙÔ ÔÛÔÛÙfi Ê·Ú̷΢ÙÈ΋˜ ηٿ¯ÚËÛ˘ Ô˘ ·Ô‰fiıËΠ۠ڈÙÔ‚Ô˘Ï›· ÙˆÓ ·ÛıÂÓÒÓ, ÛÙËÓ ·14 that recorded in the work of Hatziyannis et al.2 and Bazopoulou3 (7% and 6%, respectively). Although these data should be evaluated with caution, since they are derived from information provided by patients, they stress the necessity that patients with oral diseases be treated by a specialist in Oral Medicine. Studies investigating only the use of drugs in oral diseases, excluding odontogenic infections and periodontal diseases, are not found in the international literature. On the contrary, there are numerous publications about antibiotics for diseases of the dental pulp or periapical and periodontal tissues administrated by dentists. Regarding antibiotics, which hold the top spot internationally on dental prescribing5, two types of studies have been conducted. The first category includes questionnaires with hypothetical cases of patients, which were sent to general dentists, asking them to identify in which cases, in their opinion, patients should take antibiotics6-13. Among those reviews, only Jaunay et al.8 refer to oral mucosal diseases, and include in patients’ complaints Hellenic Stomatological Review 57: 9-17, 2013 EÚ¢ÓËÙÈ΋ EÚÁ·Û›· Research Study ÚÔ‡Û· ÂÚÁ·Û›· ·˘Ùfi ˘ÔÏÔÁ›ÛÙËΠ۠34% Î·È Â›Ó·È Û¯Â‰fiÓ ˘ÂÚ‰ÈÏ¿ÛÈÔ ·fi ÙÔ 19% ÛÙËÓ ÂÚÁ·Û›· ÙˆÓ X·Ù˙ËÁÈ¿ÓÓË Î·È Û˘Ó.2 (19%), ·ÏÏ¿ ÌÈÎÚfiÙÂÚÔ ·fi ·˘Ù¿ ÙˆÓ ÂÚ¢ÓÒÓ ÙˆÓ ™ÎÏ·‚Ô‡ÓÔ˘ Î·È ¢Ú›ÎÔ˘4 (51%) Î·È Ù˘ M·˙ÔÔ‡ÏÔ˘3 (57%). ™ËÌÂÈÒÓÂÙ·È, ˆÛÙfiÛÔ, ˆ˜ ÂÂȉ‹ fiϘ ÔÈ ÌÂϤÙ˜ ‹Ù·Ó ·Ó·‰ÚÔÌÈΤ˜, ÙfiÛÔ ÛÙËÓ ·ÚÔ‡Û·, fiÛÔ Î·È Û ·˘Ù‹ ÙˆÓ X·Ù˙ËÁÈ¿ÓÓË Î·È Û˘Ó.2 Û ¤Ó· ÌÂÁ¿ÏÔ ·ÚÈıÌfi ·ÛıÂÓÒÓ ‰ÂÓ ˘‹Ú¯·Ó ÛÙÔȯ›· ÁÈ· ÙÔ ÔÈÔ˜ ·ÔÊ¿ÛÈÛ ÙË ¯ÔÚ‹ÁËÛË (27% Î·È 41%, ·ÓÙ›ÛÙÔȯ·), ÁÂÁÔÓfi˜ Ô˘ ÂӉ¯Ô̤ӈ˜ ÂËÚ¿˙ÂÈ Ù· ÔÛÔÛÙ¿. TÔ ÌfiÓÔ ÂÓı·ÚÚ˘ÓÙÈÎfi ÛÙÔÈ¯Â›Ô ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ‹Ù·Ó ÙÔ ÔÛÔÛÙfi ÔÏ˘Ê·Ú̷Λ·˜ (32%) Ô˘ ‹Ù·Ó ÌÂȈ̤ÓÔ Û ۯ¤ÛË Ì ÙȘ ÚÔËÁÔ‡ÌÂÓ˜ ÌÂϤÙ˜, ÛÙȘ Ôԛ˜ ‹Ù·Ó 52,5%2, 72,5%4 Î·È 58%3. MÂÁ¿ÏÔ ÔÛÔÛÙfi Ù˘ ·‰ÈηÈÔÏfiÁËÙ˘ Û˘ÓÙ·ÁÔÁÚ¿ÊËÛ˘, Û‡Ìʈӷ Ì ٷ ÛÙÔȯ›· Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘, ¤ÁÈÓ ·fi È·ÙÚÔ‡˜ øP§, ÔÈ ÔÔ›ÔÈ ÌfiÓÔÈ ÙÔ˘˜ ‹ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ¿ÏϘ È·ÙÚÈΤ˜ ÂȉÈÎfiÙËÙ˜ ¤ÊÂÚ·Ó ÙËÓ Â˘ı‡ÓË Ù˘ Ê·Ú̷΢ÙÈ΋˜ ηٿ¯ÚËÛ˘ ÛÙÔ 15,3% ÙˆÓ ÂÚÈÙÒÛÂˆÓ (70 ÂÚÈÙÒÛÂȘ), ÔÛÔÛÙfi Û·ÊÒ˜ ÌÂÁ·Ï‡ÙÂÚÔ ·fi ·˘Ùfi Ô˘ ›¯Â ηٷÁÚ·Ê› ÛÙȘ ÂÚÁ·Û›Â˜ ÙˆÓ X·Ù˙ËÁÈ¿ÓÓË Î·È Û˘Ó.2 Î·È Ù˘ M·˙ÔÔ‡ÏÔ˘3 (7% Î·È 6%, ·ÓÙ›ÛÙÔȯ·) . AÓ Î·È Ù· ÛÙÔȯ›· ·˘Ù¿ Ú¤ÂÈ Ó· ÂÎÙÈÌÒÓÙ·È Ì ÂÈʇϷÍË, ηıÒ˜ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙȘ ÏËÚÔÊÔڛ˜ Ô˘ ‰›ÓÔ˘Ó ÔÈ ·ÛıÂÓ›˜, ÂÈÛËÌ·›ÓÔ˘Ó ÙËÓ ·Ó¿ÁÎË ·ÓÙÈÌÂÙÒÈÛ˘ ÙˆÓ ·ÛıÂÓÒÓ Ì ÛÙÔÌ·ÙÔÏÔÁÈο ÓÔÛ‹Ì·Ù· ·fi ÂȉÈÎÔ‡˜ ÛÙÔÌ·ÙÔÏfiÁÔ˘˜. MÂϤÙ˜ Ô˘ ‰ÈÂÚ¢ÓÔ‡Ó ·ÔÎÏÂÈÛÙÈο ÙËÓ ¯Ú‹ÛË Ê·ÚÌ¿ÎˆÓ Û ÓÔÛ‹Ì·Ù· ÙÔ˘ ÛÙfiÌ·ÙÔ˜, ÂÍ·ÈÚÔ˘Ì¤ÓˆÓ ÙˆÓ Ô‰ÔÓÙÔÁÂÓÒÓ ÏÔÈÌÒÍÂˆÓ Î·È ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÓfiÛˆÓ, ‰ÂÓ ·Ó¢ڛÛÎÔÓÙ·È ÛÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›·. AÓÙ›ıÂÙ·, ˘¿Ú¯ÂÈ ÏËıÒÚ· ‰ËÌÔÛȇÛÂˆÓ Û¯ÂÙÈο Ì ÙËÓ ˘ÂÚ‚ÔÏÈ΋ ¯ÔÚ‹ÁËÛË ·ÓÙÈ‚ÈÔÙÈÎÒÓ ÁÈ· ÙȘ ·ı‹ÛÂȘ ÙÔ˘ ÔÏÊÔ‡, ÙˆÓ ÂÚÈ·ÎÚÔÚÚÈ˙ÈÎÒÓ Î·È ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ ·fi Ô‰ÔÓÙÈ¿ÙÚÔ˘˜. ø˜ ÚÔ˜ Ù· ·ÓÙÈ‚ÈÔÙÈο, Ô˘ η٤¯Ô˘Ó ‰ÈÂıÓÒ˜ ÙËÓ ÚÒÙË ı¤ÛË ÛÙËÓ Ô‰ÔÓÙÈ·ÙÚÈ΋ Û˘ÓÙ·ÁÔÁÚ¿ÊËÛË5, ¤¯Ô˘Ó ‰ÈÂÍ·¯ı› ‰‡Ô ›‰Ë ÌÂÏÂÙÒÓ. H ÚÒÙË Î·ÙËÁÔÚ›· ÂÚÈÏ·Ì‚¿ÓÂÈ ÂÚˆÙËÌ·ÙÔÏfiÁÈ· Ì ˘ÔıÂÙÈο ÛÂÓ¿ÚÈ· ÂÚÈÙÒÛÂˆÓ ·ÛıÂÓÒÓ Ô˘ ÛÙ¿ÏıËÎ·Ó Û ÁÂÓÈÎÔ‡˜ Ô‰ÔÓÙÈ¿ÙÚÔ˘˜, ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ˙ËÙ‹ıËΠӷ ÚÔÛ‰ÈÔÚ›ÛÔ˘Ó Û ÔȘ, ηٿ ÙË ÁÓÒÌË ÙÔ˘˜, ÂÚÈÙÒÛÂȘ ÔÈ ·ÛıÂÓ›˜ ¤¯ÚË˙·Ó ·ÓÙÈ‚ÈÔÙÈ΋˜ ·ÁˆÁ‹˜613 . MÂٷ͇ ·˘ÙÒÓ ÙˆÓ ‰ËÌÔÛȇۈÓ, ·Ó·ÊÔÚ¿ Û ‚Ï¿‚˜ ÙÔ˘ ÛÙÔÌ·ÙÈÎÔ‡ ‚ÏÂÓÓÔÁfiÓÔ˘ ˘¿Ú¯ÂÈ ÌfiÓÔ ÛÙËÓ ÂÚÁ·Û›· ÙˆÓ Jaunay Î·È Û˘Ó.8, ÛÙËÓ ÔÔ›· ÛÙȘ Èı·Ó¤˜ ·Èٛ˜ ÚÔÛ¤Ï¢Û˘ ·ÛıÂÓÒÓ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·Ó Ù· Ôͤ· ÙÚ·˘Ì·ÙÈο ¤ÏÎË Î·È Ë ‰ËÌÈÔ˘ÚÁ›· ÂÚ˘ı‹Ì·ÙÔ˜ Û ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ·Ê·ÈÚÔ‡Û·Ó ÙȘ Ô‰ÔÓÙÔÛÙÔȯ›Â˜ ÙÔ˘˜ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ‡ÓÔ˘. Afi ÙÔ˘˜ 68 Ô‰ÔÓÙÈ¿ÙÚÔ˘˜ Ô˘ Û˘ÌÌÂÙ›¯·Ó ÛÙËÓ ¤Ú¢ӷ, ÙÔ 17% ı· ¯ÔÚËÁÔ‡Û ·ÓÙÈ‚ÈÔÙÈÎfi ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ÙÚ·˘Ì·ÙÈÎÔ‡ ¤ÏÎÔ˘˜, ÂÓÒ ÙÔ 19% ı· Û˘ÓÙ·ÁÔÁÚ·ÊÔ‡Û ·ÓÙÈÌ˘ÎËÙÈ·ÛÈÎfi ÁÈ· ÙË ÛÙÔÌ·Ù›Ùȉ· ·fi Ô‰ÔÓÙÔÛÙÔȯ›·, ¯ˆÚ›˜ Ù·˘Ùfi¯ÚÔÓË Û‡ÛÙ·ÛË ÁÈ· ·ÔÌ¿ÎÚ˘ÓÛË Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ‡ÓÔ˘8. ™ÙË ‰Â‡ÙÂÚË Î·ÙËÁÔÚ›· ÌÂÏÂÙÒÓ ˙ËÙ‹ıËΠ·fi ÁÂÓÈÎÔ‡˜ Ô‰ÔÓÙÈ¿ÙÚÔ˘˜ ÁÈ· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ·fi Ì›· ¤ˆ˜ ¤ÓÙÂη ‚‰ÔÌ¿‰Â˜ Ó· ηٷÁÚ¿„Ô˘Ó ÙÔÓ ·ÚÈıÌfi ÙˆÓ ·ÛıÂÓÒÓ Hellenic Stomatological Review 57: 9-17, 2013 the acute infected traumatic ulcer and denture stomatitis. Of the 68 dentists participating in that survey, 17% would provide an antibiotic for the treatment of traumatic ulcer, while 19% would prescribe an antifungal for the denture stomatitis without a simultaneous recommendation for removal of the denture during sleep8. In the second category, general dentists were asked to record the number of patients to whom they prescribed any drug for a period of one to eleven weeks, while, in the event of an antibiotic, and to complete the drug type formulation and the administration instructions (dosage and duration of intake)14-18. Among these researches, examples of drug abuse in the field of Oral Medicine were found only in two studies from Norway14, 16. In these studies, which were within 14 years, it appeared that the rates of irrational antibiotic prescriptions increased significantly for stomatitis (from 17% to 37%) and oral herpes simplex (from 10% to 21%)14, 16. CONCLUSIONS In conclusion, drug abuse is a phenomenon repeated with the same frequency over the years. The delay in diagnosis and the patient’s exposure to the risk of complications of drug abuse in Oral Medicine and Pathology requires, on the one hand, that the medical community be informed about the rational use of medicines and, on the other, the conscientiousness of dental and medical representatives, who will undertake to treat only the cases of patients in their field of knowledge and expertise. Contact details: Eleni-Marina Kalogirou [email protected] 15 EÚ¢ÓËÙÈ΋ EÚÁ·Û›· Research Study ÛÙÔ˘˜ ÔÔ›Ô˘˜ ¯ÔÚ‹ÁËÛ·Ó Î¿ÔÈÔ Ê¿ÚÌ·ÎÔ, ÂÓÒ ÛÙËÓ ÂÚ›ÙˆÛË fiÔ˘ Ë Û˘ÓÙ·ÁÔÁÚ¿ÊËÛË ·ÊÔÚÔ‡Û Û ·ÓÙÈ‚ÈÔÙÈÎfi, Ó· Û˘ÌÏËÚÒÓÔ˘Ó ÙÔ Â›‰Ô˜ ÙÔ˘ Û΢¿ÛÌ·ÙÔ˜ Î·È ÙȘ Ô‰ËÁ›Â˜ ¯ÔÚ‹ÁËÛ˘ (‰ÔÛÔÏÔÁ›· Î·È ‰È¿ÚÎÂÈ· Ï‹„˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘)14-18. AÓ¿ÌÂÛ· ÛÙȘ ·Ú·¿Óˆ ÌÂϤÙ˜, ·Ú·‰Â›ÁÌ·Ù· Ê·Ú̷΢ÙÈ΋˜ ηٿ¯ÚËÛ˘ ÛÙÔ ¯ÒÚÔ Ù˘ ÛÙÔÌ·ÙÔÏÔÁ›·˜ ·Ó¢ڛÛÎÔÓÙ·È ÌfiÓÔ Û ‰‡Ô ÌÂϤÙ˜ ·fi ÙË NÔÚ‚ËÁ›·14, 16. ™ÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ Ô˘ ›¯·Ó ¯ÚÔÓÈ΋ ·fiÛÙ·ÛË 14 ÂÙÒÓ, Ê¿ÓËΠˆ˜ ·˘Í‹ıËÎ·Ó ÛËÌ·ÓÙÈο Ù· ÔÛÔÛÙ¿ ·‰ÈηÈÔÏfiÁËÙ˘ Û˘ÓÙ·ÁÔÁÚ¿ÊËÛ˘ ·ÓÙÈ‚ÈÔÙÈÎÒÓ ÁÈ· ÙË ÛÙÔÌ·Ù›Ùȉ· (·fi 17% Û 37%) Î·È ÙÔÓ ·Ïfi ¤ÚËÙ· ÙÔ˘ ÛÙfiÌ·ÙÔ˜ (·fi 10% Û 21%)14, 16. ™YM¶EPA™MATA ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ·‰ÈηÈÔÏfiÁËÙË ¯ÔÚ‹ÁËÛË Ê·ÚÌ¿ÎˆÓ ·ÔÙÂÏ› ¤Ó· Ê·ÈÓfiÌÂÓÔ Ô˘ ·ӷϷ̂¿ÓÂÙ·È Ì ÙËÓ ›‰È· Û˘¯ÓfiÙËÙ· ÛÙËÓ ¿ÚÔ‰Ô ÙˆÓ ÂÙÒÓ. H ηı˘ÛÙ¤ÚËÛË ÛÙË ‰È¿ÁÓˆÛË Î·È Ë ¤ÎıÂÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ ÛÙÔÓ Î›Ó‰˘ÓÔ ÙˆÓ ÂÈÏÔÎÒÓ Ô˘ Û˘Ó¿ÁÂÙ·È Ë Î·Ù¿¯ÚËÛË Ê·ÚÌ¿ÎˆÓ ÛÙË ÛÙÔÌ·ÙÔÏÔÁ›·, ÂÈ‚¿ÏÏÂÈ ·ÊÂÓfi˜ ÙËÓ ÂÓË̤ڈۋ Ù˘ È·ÙÚÈ΋˜ ÎÔÈÓfiÙËÙ·˜ ÁÈ· ÙËÓ ÔÚıÔÏÔÁÈ΋ ¯Ú‹ÛË ÙˆÓ Ê·ÚÌ¿ÎˆÓ Î·È ·ÊÂÙ¤ÚÔ˘ ÙËÓ Â˘Û˘ÓÂȉËÛ›· ÙˆÓ ÂÎÚÔÛÒˆÓ ÙÔ˘ Ô‰ÔÓÙÈ·ÙÚÈÎÔ‡ Î·È È·ÙÚÈÎÔ‡ ¯ÒÚÔ˘, Ô˘ ı· ·Ó·Ï·Ì‚¿ÓÔ˘Ó Ó· ıÂÚ·Â‡Ô˘Ó ÌfiÓÔ ÙȘ ÂÚÈÙÒÛÂȘ ·ÛıÂÓÒÓ Ô˘ ¿ÙÔÓÙ·È ÙˆÓ ÁÓÒÛÂˆÓ Î·È Ù˘ ÂÍÂȉ›ÎÂ˘Û‹˜ ÙÔ˘˜. BIB§IO°PAºIA 1. 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Kakoei S, Raoof M, Baghaei F, Adhami S: Pattern of antibiotic prescription among dentists in Iran. Iran Endod J 2007; 2 (1): 19-23. 13. Murti A, Morse Z: Dental antibiotic prescription in Fijian adults. Int Dent J 2007; 57 (2): 65-70. 14. Preus HR, Albandar JM, Gjermo P: Antibiotic prescribing practices among Norwegian dentists. Scand J Dent Res 1992; 100 (4): 232-235. 15. Dailey YM, Martin MV: Are antibiotics being used appropriately for emergency dental treatment? Br Dent J 2001; 191 (7): 391-393. 16. Demirbas F, Gjermo PE, Preus HR: Antibiotic prescribing practices among Norwegian dentists. ActaOdontolScand 2006; 64 (6): 355-359. 17. Mainjot A, D’Hoore W, Vanheusden A, Van Nieuwenhuysen JP: Antibiotic prescribing in dental practice in Belgium. IntEndod J 2009; 42 (12): 1112-1117. 18. Vessal G, Khabiri A, Mirkhani H, Cookson BD, Askarian M: Study of antibiotic prescribing among dental practitioners in Shiraz, Islamic Republic of Iran. East Mediterr Health J 2011; 17 (10): 763-769. ¢È‡ı˘ÓÛË ÁÈ· ÂÈÎÔÈÓˆÓ›·: EϤÓË-M·Ú›Ó· K·ÏÔÁ‹ÚÔ˘ [email protected] Hellenic Stomatological Review 57: 9-17, 2013 17 £¤Ì· ∫ÏÈÓÈÎÔ‡ ∂ӉȷʤÚÔÓÙÔ˜ Clinical Interest ∫ÏÈÓÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘¯ˆÙ‹˜ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜ ·fi Ô‰ÔÓÙÔÛÙÔȯ›Â˜. ¶·ÚÔ˘Û›·ÛË ÂÚÈÛÙ·ÙÈÎÔ‡ Î·È ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ó·ÛÎfiËÛË ª. ™ˆÙËÚ›Ô˘*, ¡. ¶ÔÏ˘¯ÚÔÓ¿Î˘*, ºÚ. ºÚ·ÁΛÛÎÔ˜**, ∂. ™Ù·‡ÚÔ˘** Clinical management of epulis fissuratum: Case presentation and literature review M. Sotiriou*, N. Polychronakis*, Fr. Fragiskos**, E. Stavrou** ¶EPI§HæH SUMMARY ™ÙËÓ ÂÚÁ·Û›· ·˘Ù‹ ÂÚÈÁÚ¿ÊÂÙ·È Ì›· ̤ıÔ‰Ô˜ ‰È·Ù‹ÚËÛ˘ ÙÔ˘ ‚¿ıÔ˘˜ Ù˘ ÚÔÛÙÔÌȷ΋˜ ·‡Ï·Î·˜ fiˆ˜ ·ÎÚÈ‚Ò˜ ÚÔ·ÙÂÈ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË Ù˘¯ˆÙ‹˜ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜ ·fi ˘ÂÚÂÎÙ·ÙÈο ÙÂÚ‡ÁÈ· Ô‰ÔÓÙÔÛÙÔȯ›·˜. H ̤ıÔ‰Ô˜ ·˘Ù‹ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ Î·Ù·Û΢‹ Ù˘ ÔÏÈ΋˜ Ô‰ÔÓÙÔÛÙÔȯ›·˜ - ÚÈÓ ÙËÓ ·Ê·›ÚÂÛË Ù˘ ‚Ï¿‚˘ - ¿ӈ ÛÙÔ ÔÚÈÛÙÈÎfi ÂÎÌ·ÁÂ›Ô ·fi Á‡„Ô ÙÔ ÔÔ›Ô ¤¯ÂÈ ÙÚÔÔÔÈËı› ‚¿ÛÂÈ ÙÔ˘ ÂÈı˘ÌËÙÔ‡ ÙÂÏÈÎÔ‡ Û¯‹Ì·ÙÔ˜ Ù˘ ÚÔÛÙÔÌȷ΋˜ ·‡Ï·Î·˜, fiˆ˜ ·˘Ùfi ı· ¤¯ÂÈ ‰È·ÌÔÚʈı› ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË. H ÙÔÔı¤ÙËÛË Ù˘ ÚÔηٷÛ΢·Ṳ̂Ó˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ Á›ÓÂÙ·È ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË Ù˘ ˘ÂÚÏ·Û›·˜ Î·È ÙË Û˘ÚÚ·Ê‹ ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜. The purpose of this study is to describe how the depth and shape of the vestibular sulcus was maintained, after the surgical removal of an epulis fissuratum, caused by overextended dentures. The hyperplastic lesion covered the anterior area of the residual ridges and the vestibular sulcus. The technique used entailed the construction of a complete denture, before the lesion was excised, on the modified working cast reflecting the final desirable sulcus shape, as expected to be after surgery. The denture was placed in situ immediately after the surgical excision of the epulis fissuratum to maintain the vestibular sulcus depth. Key Words: complete dentures, overextended denture, epulis fissuratum. §¤ÍÂȘ ÎÏÂȉȿ: ÔÏÈΤ˜ Ô‰ÔÓÙÔÛÙÔȯ›Â˜, ˘ÂÚÂÎÙ·ÙÈο ÙÂÚ‡ÁÈ· Ô‰ÔÓÙÔÛÙÔȯ›·˜, Ù˘¯ˆÙ‹ ÈÓ҉˘ ˘ÂÚÏ·Û›· ·fi Ô‰ÔÓÙÔÛÙÔȯ›·. * ∂›ÎÔ˘ÚÔ˜ ∫·ıËÁËÙ‹˜ ∫ÈÓËÙ‹˜ ¶ÚÔÛıÂÙÈ΋˜ O‰ÔÓÙÈ·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ∂∫¶∞ ** ∞Ó·ÏËÚˆÙ‹˜ ∫·ıËÁËÙ‹˜ ™ÙÔÌ·ÙÈ΋˜ Î·È °Ó·ıÔÚÔÛˆÈ΋˜ ÃÂÈÚÔ˘ÚÁÈ΋˜ O‰ÔÓÙÈ·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ∂∫¶∞ ÂÏÏËÓÈο ÛÙÔÌ·ÙÔÏÔÁÈο ¯ÚÔÓÈο 57: 19-26, 2013 ·ÚÂÏ‹ÊıË 12/3/2013 - ÂÎÚ›ıË 19/3/2013 * Assistant Professor, Removable Prosthodontics, Dental School, University of Athens ** Associate Professor, Oral & Maxillofacial Surgery, Dental School, University of Athens Hellenic Stomatological Review 57: 19-26, 2013 paper received 12/3/2013 - accepted 19/3/2013 19 £¤Ì· ∫ÏÈÓÈÎÔ‡ ∂ӉȷʤÚÔÓÙÔ˜ Clinical Interest EI™A°ø°H INTRODUCTION H Ù˘¯ˆÙ‹ ÈÓ҉˘ ˘ÂÚÏ·Û›· ·fi Ô‰ÔÓÙÔÛÙÔȯ›· ‹ ˘ÂÚÏ·Û›· ·fi Ô‰ÔÓÙÔÛÙÔȯ›· (epulis fissuratum) Â›Ó·È ·ÓÙ›‰Ú·ÛË ÙÔ˘ ÛÙÔÌ·ÙÈÎÔ‡ ‚ÏÂÓÓÔÁfiÓÔ˘ Û ̷ÎÚÔ¯ÚfiÓÈÔ Ì˯·ÓÈÎfi ÂÚÂıÈÛÌfi1-4. OÈ ˘ÂÚÏ·ÛÙÈÎÔ› ÈÛÙÔ› ·˘Í¿ÓÔÓÙ·È, ·ÚÂÌ‚·ÏÏfiÌÂÓÔÈ ÌÂٷ͇ ÙÔ˘ ÔÚ›Ô˘ Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ Î·È ÙÔ˘ ÚÔÛÙÔÌÈ·ÎÔ‡ ‚ÏÂÓÓÔÁfiÓÔ˘, ÚÔηÏÒÓÙ·˜ ÙËÓ Î·Ù·ÎÚ¿ÙËÛË ˘ÔÏÂÈÌÌ¿ÙˆÓ ÙÚÔÊ‹˜ Î·È ÙËÓ ·Ó¿Ù˘ÍË ÌÈÎÚÔ‚›ˆÓ3. Œ¯ÂÈ ·Ó·ÊÂÚı› fiÙÈ Ë Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ Ù˘ ‚Ï¿‚˘ Û ¿ÙÔÌ· Ô˘ ÊÔÚÔ‡Ó Ô‰ÔÓÙÔÛÙÔȯ›Â˜ Î˘Ì·›ÓÂÙ·È ·fi 5-10%5, ÔÛÔÛÙ¿ Ù· ÔÔ›· Â›Ó·È ÌÈÎÚfiÙÂÚ· ·fi ·˘Ù¿ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ÓÂÒÙÂÚ˜ ¤Ú¢Ó˜ ÛÙË BÚ·˙ÈÏ›· 16,7%6 Î·È 29,4%7. ™Â ÚfiÛÊ·ÙË ¤Ú¢ӷ Ô˘ Ú·ÁÌ·ÙÔÔÈ‹ıËΠÛÙËÓ TÔ˘ÚΛ· Î·È Û ‰Â›ÁÌ· 64 ·ÛıÂÓÒÓ ÙÔ ÔÛÔÛÙfi ‹Ù·Ó 4,2%8, ·ÔÙ¤ÏÂÛÌ· Ô˘ Â›Ó·È ·ÚfiÌÔÈÔ Ì ·Ï·ÈfiÙÂÚË ÌÂϤÙË ÙˆÓ Xie Î·È Û˘Ó.9, Ì ÙËÓ Î¿Ùˆ ÁÓ¿ıÔ Ó· Â›Ó·È ÂÚÈÛÛfiÙÂÚÔ ÂÈÚÚ‹˜ Û ۯ¤ÛË Ì ÙËÓ ¿Óˆ. ™Â ÌÂϤÙË fiÔ˘ ·Ó·Ï‡ıËΠÌË Ù˘¯·›Ô ‰Â›ÁÌ· ·ÛıÂÓÒÓ ÔÈ ÔÔ›ÔÈ ·Ó¤ÊÂÚ·Ó ‰È¿ÊÔÚ· ÚÔ‚Ï‹Ì·Ù· Ì ÙȘ Ô‰ÔÓÙÔÛÙÔȯ›Â˜, ÙÔ ÔÛÔÛÙfi Ù˘ ÂÌÊ¿ÓÈÛ˘ ˘ÂÚÏ·Û›·˜ ·fi Ô‰ÔÓÙÔÛÙÔȯ›· (epulis fissuratum) ‹Ù·Ó 31,7%10. Denture - induced fibrous inflammatory hyperplasia (epulis fissuratum) is a reaction of the oral mucosa to long-term mechanical irritation1-4. Hyperplastic tissue appears between denture borders and the vestibular mucosa and this encourages trapping of food residues and microbial growth products3. Reported incidence of such lesion in denture wearers is around 5-10%5, but these rates are lower than reported in more recent studies from Brazil, i.e. 16.7%6 and 29.4%7. In a recent research study carried out in Turkey with a sample of 64 patients, the corresponding rates were 4.2%8, similar to those of an older study by Xie et al.9, with the mandible being more vulnerable than the maxilla. In a study analysing a non-randomised sample of patients reporting various denture issues, epulis fissuratum appeared in 31.7% of them10. AITIO§O°IA H ·ÚÈ· ·ÈÙ›· Ù˘ ‚Ï¿‚˘ Â›Ó·È Ù· ˘ÂÚÂÎÙ·ÙÈο ÙÂÚ‡ÁÈ· Ô‰ÔÓÙÔÛÙÔȯÈÒÓ ÙˆÓ ÔÔ›ˆÓ Ë ÂÊ·ÚÌÔÁ‹ ÛÙÔ˘˜ ˘ÔΛÌÂÓÔ˘˜ ÈÛÙÔ‡˜ ‰ÂÓ Â›Ó·È ÈηÓÔÔÈËÙÈ΋1-3, 11-14. ¶ÔÏϤ˜ ÊÔÚ¤˜ Î·È ÌfiÓÔ Ë Î·Î‹ ÂÊ·ÚÌÔÁ‹ Ù˘ ‚¿Û˘ Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÙË ‚Ï¿‚Ë4, 5, 15, 16. H ¤Ú·Ó ÙÔ˘ Ê˘ÛÈÔÏÔÁÈÎÔ‡ ¤ÎÙ·ÛË ÙˆÓ ÙÂÚ˘Á›ˆÓ Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ›Ù Ù˘ Ï·Óı·Ṳ̂Ó˘ ÔÚÈÔı¤ÙËÛ‹˜ ÙÔ˘˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ηٷÛ΢‹˜ ÙˆÓ Ô‰ÔÓÙÔÛÙÔȯÈÒÓ Â›Ù Ù˘ ·ÔÚÚfiÊËÛ˘ ÙˆÓ Ê·ÙÓÈ·ÎÒÓ ·ÎÚÔÏÔÊÈÒÓ Ì ·ÎfiÏÔ˘ıÔ ÙÔ «‚‡ıÈÛÌ·» ÙˆÓ ÙÂÚ˘Á›ˆÓ ÛÙÔ˘˜ Ì·Ï·ÎÔ‡˜ ÈÛÙÔ‡˜8, 15. AÓ¿ÏÔÁÔ ·ÔÙ¤ÏÂÛÌ· «‚‡ıÈÛ˘» ÙˆÓ ÙÂÚ˘Á›ˆÓ ÛÙÔ˘˜ ˘ÔΛÌÂÓÔ˘˜ ÈÛÙÔ‡˜ ÌÔÚ› Ó· ÚÔηϤÛÂÈ Ë Ï·Óı·Ṳ̂ÓË ‹ ηı’ ¤ÍÈÓ Û‡ÁÎÏÂÈÛË ÙˆÓ Ù¯ÓËÙÒÓ ‰ÔÓÙÈÒÓ13. K§INIKH EIKONA H ÎÏÈÓÈ΋ ÂÈÎfiÓ· Ù˘ Ù˘¯ˆÙ‹˜ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜ ·fi Ô‰ÔÓÙÔÛÙÔȯ›· ÔÈΛÏÏÂÈ ·fi Ì›· ̤¯ÚÈ ÔÏϷϤ˜ ·Ó·‰ÈÏÔ‡ÌÂÓ˜ Ù˘¯¤˜ Ô˘ ÂÓÙÔ›˙ÔÓÙ·È ÛÙ· ÚÔÛÙÔÌȷο ΢ڛˆ˜ fiÚÈ· ÙˆÓ ÙÂÚ˘Á›ˆÓ Ù˘4, 13 (EÈÎ. 1). O ˘ÂÚÏ·ÛÙÈÎfi˜ ÈÛÙfi˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È Û¯Â‰fiÓ ¿ÓÙÔÙ Û ÊÏÂÁÌÔÓÒ‰Ë Î·È ·ÚÎÂÙ¿ Û˘¯Ó¿ Û ÂÍÂÏΈ̤ÓË Î·Ù¿ÛÙ·ÛË Î·È Â›Ó·È Â˘Î›ÓËÙÔ˜ Î·È ˘fiÛÎÏËÚÔ˜ ηٿ ÙË „ËÏ¿ÊËÛË1, 12. OÈ ·ÛıÂÓ›˜ Û˘Ó‹ıˆ˜ ‰ÂÓ ·ÓÙÈÏ·Ì‚¿ÓÔÓÙ·È ÙËÓ ‡·ÚÍË ÙˆÓ ˘ÂÚÏ·ÛÙÈÎÒÓ ·˘ÙÒÓ ÈÛÙÒÓ ÂÂȉ‹, ηٿ ÙÔ Ï›ÛÙÔÓ, ‰ÂÓ Û˘Óԉ‡ÔÓÙ·È ·fi fiÓÔ. MfiÓÔÓ fiÙ·Ó Ë Ì¿˙· ÙÔ˘˜ ·˘ÍËı› ·ÚÎÂÙ¿ ÔÈ ·ÛıÂÓ›˜ ·Ú¯›˙Ô˘Ó Ó· ·ÓËÛ˘¯Ô‡Ó (ηÚÎÈÓÔÊÔ‚›·)2. ™Â ÂÏ¿¯ÈÛÙ˜ ÂÚÈÙÒÛÂȘ ¤¯ÂÈ ·Ú·ÙËÚËı› ·Ó¿Ù˘ÍË Î·ÚÎÈÓˆÌ¿ÙˆÓ ÛÙÔ ÂÏΈÙÈÎfi ÙÚ·‡Ì· Ù˘ ˘ÂÚÏ·Û›·˜13, 17. AETIOLOGY The lesion is mainly caused by overextended denture flanges1-3, 11-14 and/or an ill-fitting denture base4, 5, 15, 16. Overextension of denture flanges may be due to either erroneous bordering during denture construction or alveolar ridge resorption, which allows the flanges to “dig into” soft tissues8, 15. Flanges may “dig into” the underlying tissues in a similar way because of malocclusion of the artificial teeth13. CLINICAL APPEARANCE Clinically, epulis fissuratum caused by dentures may present one or more folds in the vestibular sulcus, mainly around denture borders4, 13 (Fig. 1). The hyperplastic tissue almost always appears to be inflammatory and often ulcerated; it is mobile and moderately hard on palpation1, 12 . Patients are not usually aware of such hyperplastic tissues because these usually cause no pain. Only when the lesion mass increases do patients start to show concern (cancer phobia)2. In very few cases cancerous lesions have been observed on the ulcerated hyperplastic lesion13, 17. £EPA¶EIA EÈÎ. 1: KÏÈÓÈ΋ ÂÈÎfiÓ· Ù˘¯ˆÙ‹˜ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜. H ıÂڷ›· Ô˘ ÚÔÙ›ÓÂÙ·È, ·fi ÙÔ˘˜ ÂÚÈÛÛÔÙ¤ÚÔ˘˜ Fig. 1: Epulis fissuratum - clinical appearance. 20 Hellenic Stomatological Review 57: 19-26, 2013 £¤Ì· ∫ÏÈÓÈÎÔ‡ ∂ӉȷʤÚÔÓÙÔ˜ Clinical Interest Û˘ÁÁÚ·Ê›˜ Â›Ó·È Î·Ù’ ·Ú¯¿˜ Û˘ÓÙËÚËÙÈ΋ ηÈ, ÂÊ’ fiÛÔÓ Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ‰ÂÓ Â›Ó·È ÈηÓÔÔÈËÙÈο, Û˘ÌÏËÚÒÓÂÙ·È Ì ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÍ·›ÚÂÛË Ù˘ ˘ÂÚÏ·Û›·˜2, 3, 11, 13, 14, 18-20 . AÓÙ›ıÂÙ· ÔÈ ¯ÂÈÚÔ˘ÚÁÔ› ÛÙfiÌ·ÙÔ˜ Û˘ÓÈÛÙÔ‡Ó ÌfiÓÔÓ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ‚Ï¿‚˘, ȉȷ›ÙÂÚ· fiÙ·Ó ÙÔ Ì¤ÁÂıÔ˜ Ù˘ Â›Ó·È ÛËÌ·ÓÙÈÎfi1, 12, 15-17. ™ÎÔfi˜ Ù˘ ıÂڷ›·˜ Â›Ó·È ·Ú¯Èο Ô ÂÚÈÔÚÈÛÌfi˜ ÙÔ˘ ÌÂÁ¤ıÔ˘˜ Ù˘ ˘ÂÚÏ·Û›·˜ Î·È ÛÙË Û˘Ó¤¯ÂÈ·, ÂÊ’ fiÛÔÓ Ë ‚Ï¿‚Ë ‰ÂÓ ˘Ô¯ˆÚ‹ÛÂÈ Û ÈηÓÔÔÈËÙÈÎfi ‚·ıÌfi, Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË ÙÔ˘ ˘ÂÚÏ·ÛÙÈÎÔ‡ ÈÛÙÔ‡11, 19. O ÂÚÈÔÚÈÛÌfi˜ Ù˘ ˘ÂÚÏ·Û›·˜ ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙËÓ ¿ÚÛË ÙÔ˘ ·ÈÙ›Ô˘, ·ÊÂÓfi˜ ÌÂÈÒÓÔÓÙ·˜ ÙÔ Ì‹ÎÔ˜ ÙÔ˘ ÙÂÚ˘Á›Ô˘ Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ ·ÓÙ›ÛÙÔȯ· Ì ÙË ‚Ï¿‚Ë, ¤ÙÛÈ ÒÛÙ ӷ ·¤¯ÂÈ ·fi ·˘Ù‹Ó ÙÔ˘Ï¿¯ÈÛÙÔÓ 1 ¯ÈÏ., ·ÊÂÙ¤ÚÔ˘ ÂÚÈÔÚ›˙ÔÓÙ·˜ fiÛÔÓ ÙÔ ‰˘Ó·ÙfiÓ ÙË ¯Ú‹ÛË Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜. ™Â ‚·Ú‡ÙÂÚ˜ ηٷÛÙ¿ÛÂȘ ·Ê·ÈÚÂ›Ù·È fiÏÔ ÙÔ ÙÂÚ‡ÁÈÔ Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ Î·È ·Ú¿ÏÏËÏ· Û˘ÓÈÛÙ¿Ù·È Ë ·ÔÊ˘Á‹ ¯Ú‹Û˘ ÙˆÓ Ô‰ÔÓÙÔÛÙÔȯÈÒÓ ÁÈ· fiÛÔ ÙÔ ‰˘Ó·ÙfiÓ ÂÚÈÛÛfiÙÂÚÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·2 ‹ Î·È Î·ıfiÏÔ˘ ¯Ú‹ÛË ÙÔ˘˜ Ì ·Ú¿ÏÏËÏË Ì¿Ï·ÍË Ù˘ ÂÚÈÔ¯‹˜19. ŸÙ·Ó ÔÈ Ô‰ÔÓÙÔÛÙÔȯ›Â˜ ¤¯Ô˘Ó ÌÂȈ̤ÓË Û˘ÁÎÚ¿ÙËÛË Î·È ÛÙ·ıÂÚfiÙËÙ· Á›ÓÂÙ·È Ì›· ÚÔÛˆÚÈÓ‹ ·Ó·ÚÔÛ·ÚÌÔÁ‹ Ù˘ ‚¿Û˘ ÙÔ˘˜ Ì οÔÈÔ ˘ÏÈÎfi ·ÔηٿÛÙ·Û˘ ÙˆÓ ÈÛÙÒÓ (tissue conditioner) Ë ·ÓÙÈηٿÛÙ·ÛË ÙÔ˘ ÔÔ›Ô˘ ı· Ú¤ÂÈ Ó· Á›ÓÂÙ·È Î¿ı 4-6 Ë̤Ú˜20. H ηϋ ÛÙÔÌ·ÙÈ΋ ˘ÁÈÂÈÓ‹, Ô ¤ÏÂÁ¯Ô˜ Ù˘ Û‡ÁÎÏÂÈÛ˘ Î·È Ë ‰ÈfiÚıˆÛ‹ Ù˘, ·Ó ¯ÚÂÈ¿˙ÂÙ·È, Û˘ÌÏËÚÒÓÔ˘Ó ÙË Û˘ÓÙËÚËÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ‚Ï¿‚˘11, 14, 20. H Û˘ÓÙËÚËÙÈ΋ ıÂڷ›· ‰È·ÚΛ 4-6 ‚‰ÔÌ¿‰Â˜19, 20. ™˘Ó‹ıˆ˜ Ù· ·ÔÙÂϤÛÌ·Ù· Â›Ó·È ÈηÓÔÔÈËÙÈο. E¿Ó fï˜ Ë ‚ÂÏÙ›ˆÛË ‰ÂÓ ÎÚ›ÓÂÙ·È ÈηÓÔÔÈËÙÈ΋, ÚÔ‚·›ÓÔ˘Ì Û ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÍ·›ÚÂÛË Ù˘ ˘ÂÚÏ·Û›·˜ ¤ÙÛÈ ÒÛÙ ӷ ‰ËÌÈÔ˘ÚÁËı› ¢ÓÔ˚Îfi ˘fiÛÙڈ̷ ¿Óˆ ÛÙÔ ÔÔ›Ô ı· ηٷÛ΢·ÛıÔ‡Ó ÔÈ Ó¤Â˜ Ô‰ÔÓÙÔÛÙÔȯ›Â˜14. H ·Ê·›ÚÂÛË Ù˘ ‚Ï¿‚˘ ÌÔÚ› Ó· Á›ÓÂÈ Î·È Ì ÙË ¯ÚËÛÈÌÔÔ›ËÛË Û˘Û΢ÒÓ laser16, 21, 22. H ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË ÙˆÓ ˘ÂÚÏ·ÛÙÈÎÒÓ ÈÛÙÒÓ Î·È Ë ·Ú¿ÏÏËÏË Û˘ÚÚ·Ê‹ ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜ Èı·ÓfiÓ Ó· ÚÔηϤÛÂÈ ÂÏ¿ÙÙˆÛË ÙÔ˘ ‚¿ıÔ˘˜ Ù˘ ÚÔÛÙÔÌȷ΋˜ ·‡Ï·Î·˜, ÏfiÁˆ Ù˘ ÂÂÚ¯fiÌÂÓ˘ Ô˘ÏÒ‰Ô˘˜ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ Ú›ÎÓˆÛ˘ ÙˆÓ ÈÛÙÒÓ, Ë ÔÔ›· ı· ¤¯ÂÈ ·ÚÓËÙÈΤ˜ ÂȉڿÛÂȘ ÛÙË Û˘ÁÎÚ¿ÙËÛË Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜3. ™ÙËÓ ÂÚÁ·Û›· ·˘Ù‹ ÂÚÈÁÚ¿ÊÂÙ·È Ì›· Ù¯ÓÈ΋ Ô˘ ıˆÚÂ›Ù·È fiÙÈ ·Ô‰›‰ÂÈ ÈηÓÔÔÈËÙÈο ·ÔÙÂϤÛÌ·Ù· fiÛÔÓ ·ÊÔÚ¿ ÛÙËÓ ÚfiÏË„Ë Ù˘ Ì›ˆÛ˘ ÙÔ˘ ‚¿ıÔ˘˜ Ù˘ ÚÔÛÙÔÌȷ΋˜ ·‡Ï·Î·˜ ηٿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÍ·›ÚÂÛË Ù˘¯ˆÙ‹˜ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜ ·fi Ô‰ÔÓÙÔÛÙÔȯ›·. ANAºOPA KAI ¶EPI°PAºH TOY ¶EPI™TATIKOY °˘Ó·›Î· ËÏÈΛ·˜ 54 ÂÙÒÓ, ÚÔÛ‹Ïı ÛÙËÓ KÏÈÓÈ΋ Ù˘ KÈÓËÙ‹˜ ¶ÚÔÛıÂÙÈ΋˜ Ù˘ O‰ÔÓÙÈ·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ AıËÓÒÓ, ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ ÚÔ ÙÚÈÂÙ›·˜ ηٷÛ΢·Ṳ̂ӈÓ, ·fi ȉÈÒÙË Ô‰ÔÓÙ›·ÙÚÔ, ÔÏÈÎÒÓ Ô‰ÔÓÙÔÛÙÔȯÈÒÓ Ù˘ Ô˘ ·ÚÔ˘Û›·˙·Ó ÏËÌÌÂÏ‹ ÂÊ·ÚÌÔÁ‹ ÛÙÔ˘˜ ÈÛÙÔ‡˜, ÊıÔÚ¿ ÙˆÓ ÚÔÛı›ˆÓ ‰ÔÓÙÈÒÓ Î·È Ï·Óı·Ṳ̂ÓË Û‡ÁÎÏÂÈÛË. K·Ù¿ ÙËÓ ·Ú¯È΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠÂÎÙÂٷ̤ÓË ˘Hellenic Stomatological Review 57: 19-26, 2013 TREATMENT Most authors recommend that initial treatment should be conservative and, if results are not satisfactory, it may be supplemented by surgical excision of the hyperplastic tissue2, 3, 11, 13, 14, 18-20. On the contrary, oral surgeons recommend that epulis fissuratum should only be treated surgically, particularly if it is extensive1, 12, 15-17. It may be said that the initial treatment goal is to reduce the size of the hyperplasia and then, if it has not sufficiently receded, the hyperplastic tissue may be removed11, 19. Hyperplasia is reduced by eliminating its cause; this may be achieved by reducing the denture flange to allow at least 1 mm between its borders and the surrounding tissue and by minimizing denture use. In more serious cases the entire denture flange is removed and it is recommended that denture use should be avoided as much as possible2 or even completely, while the area affected is treated with massaging19. When there is poor denture retention and stability, its base is temporarily relined using tissue conditioner, which has to be replaced every 4-6 days20. Thorough oral hygiene and occlusion check and correction, if necessary, supplement such conservative treatment of the lesion11, 14,20. Conservative treatment usually lasts for about 4-6 weeks19, 20 and its results are generally satisfactory. However, if the improvement is not considered sufficient, the hyperplasia is surgically excised so as to create a favorable fitting surface on which to construct the new dentures14. The lesion can also be removed using laser16, 21, 22. Surgical removal of hyperplastic tissue and proper trauma closure may reduce the depth of the vestibular sulcus because of scar formation and post-surgical tissue shrinkage, both of which may have a negative effect on denture retention3. This paper describes a technique believed to provide satisfactory results in preventing the reduction of the vestibular sulcus depth following surgical removal of epulis fissuratum caused by dentures. CASE REPORT A 54 year old woman presented at the Prosthodontics Clinic of the Dental School of the University of Athens to have her dentures checked. Her complete dentures had been constructed by a private practitioner three years earlier and were ill-fitting, presenting posterior teeth wear and incorrect occlusion. Initial examination showed extensive hyperplasia in the anterior mandible area, from the 33 to the 44 tooth, due to an overextended flange in the lower anterior region. The patient reported that the hyperplasia had appeared one year before and caused her no discomfort. The patient’s history revealed that painful trauma had appeared in this oral region following denture delivery, but since the patient “tolerated the pain”, as she said, she had not sought dental aid. The painful symptoms disappeared after some time, without any modification (grinding) of the denture base to relieve them. 21 £¤Ì· ∫ÏÈÓÈÎÔ‡ ∂ӉȷʤÚÔÓÙÔ˜ Clinical Interest ÂÚÏ·Û›· ÛÙËÓ Î¿Ùˆ ÁÓ¿ıÔ Î·È Û˘ÁÎÂÎÚÈ̤ӷ ÛÙËÓ ÚfiÛıÈ· ÂÚÈÔ¯‹ ·ÓÙ›ÛÙÔȯ· ÚÔ˜ ÙÔÓ 33 ¤ˆ˜ ÙÔÓ 44 ÏfiÁˆ ˘ÂÚÂÎÙ·ÙÈÎÔ‡ ÙÂÚ˘Á›Ô˘. H ·ÛıÂÓ‹˜ ·Ó¤ÊÂÚ fiÙÈ Ë ˘ÂÚÏ·Û›· ·ÚÔ˘ÛÈ¿ÛıËΠÚÈÓ ·fi 1 ¯ÚfiÓÔ Î·È ‰ÂÓ Ù˘ ÚÔηÏÔ‡Û ηӤӷ ÂÓfi¯ÏËÌ·. Afi ÙÔ ÈÛÙÔÚÈÎfi ÚԤ΢„ fiÙÈ, ÌÂÙ¿ ÙËÓ ·Ú¯È΋ ÙÔÔı¤ÙËÛË Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ ÂÌÊ·Ó›ÛÙËÎ·Ó ÂÒ‰˘Ó· ÙÚ·‡Ì·Ù· ÛÙËÓ ÚÔ·Ó·ÊÂÚı›۷ ÂÚÈÔ¯‹ ÁÈ· Ù· ÔÔ›· fï˜ Ë ·ÛıÂÓ‹˜ «ÏfiÁˆ ·ÓÙÔ¯‹˜ ÛÙÔÓ fiÓÔ», fiˆ˜ Ì·˜ ·Ó¤ÊÂÚÂ, ‰ÂÓ ˙‹ÙËÛ ÙË ‚Ô‹ıÂÈ· Ô‰ÔÓÙÈ¿ÙÚÔ˘. T· ÂÒ‰˘Ó· Û˘ÌÙÒÌ·Ù· ÌÂÙ¿ ·fi οÔÈÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ˘Ô¯ÒÚËÛ·Ó ¯ˆÚ›˜ Ó· Á›ÓÂÈ Î·Ì›· ÙÚÔÔÔ›ËÛË (ÙÚÔ¯ÈÛÌfi˜) Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ ÁÈ· ÙËÓ ·Ó·ÎÔ‡ÊÈÛ‹ ÙÔ˘˜. °È· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ‚Ï¿‚˘, ·Ú¯Èο ·ÎÔÏÔ˘ı‹ıËÎÂ Û˘ÓÙËÚËÙÈ΋ ·ÁˆÁ‹. EÂȉ‹ fï˜ Ù· ·ÔÙÂϤÛÌ·Ù· ‰ÂÓ ‹Ù·Ó ÈηÓÔÔÈËÙÈο, ·ÔÊ·Û›ÛÙËÎÂ Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË Ù˘ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜. ™ÙÔ ‰È¿ÛÙËÌ· Ô˘ ÂÊ·ÚÌfiÛıËÎÂ Ë Û˘ÓÙËÚËÙÈ΋ ·ÁˆÁ‹ Î·È ÚÈÓ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË Ù˘ ˘ÂÚÏ·Û›·˜, ηٷÛ΢¿ÛıËΠ˙‡ÁÔ˜ Ó¤ˆÓ ÔÏÈÎÒÓ Ô‰ÔÓÙÔÛÙÔȯÈÒÓ. H ηٷÛ΢‹ Ù˘ οو Ô‰ÔÓÙÔÛÙÔȯ›·˜ ¤ÁÈÓ ÛÙÔ ÔÚÈÛÙÈÎfi ÂÎÌ·ÁÂ›Ô ÙÔ ÔÔ›Ô Â›¯Â ÙÚÔÔÔÈËı› ‚¿ÛÂÈ ÙÔ˘ ÚÔÛ‰ÔÎÔ‡ÌÂÓÔ˘ Û¯‹Ì·ÙÔ˜ Ù˘ ÚÔÛÙÔÌȷ΋˜ ·‡Ï·Î·˜ ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË (EÈÎ. 2·, 2‚ ). °È· ÙËÓ ÙÚÔÔÔ›ËÛË ÙÔ˘ ÂÎÌ·Á›Ԣ ¯ÚËÛÈÌÔÔÈ‹ıËΠÙÚÔ¯fiÏÈıÔ˜ Î·È ¯ÂÈÚÔ˘ÚÁÈ΋ Ï¿Ì· No 15. K·Ù¿ ÙË Û˘ÓÙËÚËÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·ÛıÂÓÔ‡˜ Ô˘ ·ÚÔ˘Û›·˙Â Ù˘¯ˆÙ‹ ÈÓÒ‰Ë ˘ÂÚÏ·Û›· ·fi Ô‰ÔÓÙÔÛÙÔȯ›· ·ÎÔÏÔ˘ı‹ıËÎÂ Ë ÂÍ‹˜ ıÂڷ¢ÙÈ΋ ·ÁˆÁ‹: 1. ™ÙËÓ ·Ú¯È΋ ÂͤٷÛË Ù˘ ·ÛıÂÓÔ‡˜ ÚÔÛ‰ÈÔÚ›ÛÙËÎÂ Ë ‡·ÚÍË, ÙÔ Ì¤ÁÂıÔ˜ Î·È Ë ı¤ÛË Ù˘ ˘ÂÚÏ·Û›·˜ ÛÙËÓ Î¿Ùˆ ÁÓ¿ıÔ (EÈÎ. 3). 2. ¢ÈÔÚıÒıËÎÂ Ë Û‡ÁÎÏÂÈÛË ÙˆÓ Ô‰ÔÓÙÔÛÙÔȯÈÒÓ Ô˘ ¤ÊÂÚÂ Ë ·ÛıÂÓ‹˜ Ì ηٷÁÚ·Ê‹ Ù˘ ÎÂÓÙÚÈ΋˜ Û¯¤Û˘ Î·È ÂÎÏÂÎÙÈÎfi ÙÚÔ¯ÈÛÌfi ÛÙÔÓ ·ÚıÚˆÙ‹Ú·. 3. TÚÔ¯›ÛıËΠÙÔ ˘ÂÚÂÎÙ·ÙÈÎfi ÙÂÚ‡ÁÈÔ Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ ·ÓÙ›ÛÙÔȯ· ÚÔ˜ ÙËÓ ÂÚÈÔ¯‹ Ù˘ ˘ÂÚÏ·Û›·˜ (EÈÎ. 4). 4. TÔÔıÂÙ‹ıËΠ˘ÏÈÎfi ·ÔηٿÛÙ·Û˘ ÙˆÓ ÈÛÙÒÓ Visco - gel DENTSPLY ÛÙËÓ ÂÈÊ¿ÓÂÈ· ¤‰Ú·Û˘ Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ Î·È ÛÙË Û˘Ó¤¯ÂÈ· ÂÊ·ÚÌfiÛÙËΠÛÙÔ ÛÙfiÌ· Ù˘ ·ÛıÂÓÔ‡˜ fiÔ˘ Î·È ·Ú¤ÌÂÈÓ ÁÈ· ÂÚ›Ô˘ 5 min. 5. AÔÌ·ÎÚ‡ÓıËÎÂ Ë Ô‰ÔÓÙÔÛÙÔȯ›· ·fi ÙÔ ÛÙfiÌ·, ‰È·ÌÔÚÊÒıËΠÙÔ fiÚÈfi Ù˘ Î·È ·Ê·ÈÚ¤ıËÎ·Ó ÔÈ ÂÚ›ÛÛÂȘ ÙÔ˘ ˘ÏÈÎÔ‡. 6. TÔ ˘ÏÈÎfi ·ÓÙÈηı›ÛÙ·ÙÔ Î¿ı ‚‰ÔÌ¿‰· ÁÈ· ¤Ó· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 6 ‚‰ÔÌ¿‰ˆÓ Î·È Î·ÙÂÁÚ¿ÊÂÙÔ Ë ÚfiÔ‰Ô˜. K·Ù¿ ÙËÓ ÎÏÈÓÈ΋ ÂͤٷÛË Ù˘ ˘ÂÚÏ·Û›·˜ ÌÂÙ¿ ·fi 6 ‚‰ÔÌ¿‰Â˜ Û˘ÓÙËÚËÙÈ΋˜ ·ÁˆÁ‹˜19 ‰È·ÈÛÙÒıËΠ̛ˆÛË ÙÔ˘ ·Ú¯ÈÎÔ‡ ÌÂÁ¤ıÔ˘˜ Ù˘ ˘ÂÚÏ·Û›·˜, fi¯È fï˜ Û ÈηÓÔÔÈËÙÈÎfi ‚·ıÌfi (EÈÎ. 5). H Û˘ÓÙËÚËÙÈ΋ ·ÁˆÁ‹ ‰ÂÓ Â›¯Â Ù· ·Ó·ÌÂÓfiÌÂÓ· ·ÔÙÂϤÛÌ·Ù· Î·È ·ÔÊ·Û›ÛÙËÎÂ Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË Ù˘ ‚Ï¿‚˘. 1. H ˘ÂÚÏ·Û›· ·Ê·ÈÚ¤ıËΠ̠¯ÂÈÚÔ˘ÚÁÈ΋ Ï¿Ì· No 15 Î·È ‰fiıËΠÁÈ· ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË (EÈÎ. 6). H Û˘Ú22 The patient’s initial treatment was conservative, but results were not satisfactory, so it was decided that the fibrous hyperplasia would be surgically removed. Before the surgical removal of the hyperplastic tissue and while the patient was being conservatively treated, a new pair of complete dentures was constructed. The lower denture was made on the working cast, which had been modified to comply with the vestibular sulcus to be shaped by the surgery (Fig. 2a, 2b). The cast was modified using a burr and a #15 surgical blade. The patient with epulis fissuratum caused by dentures was conservatively treated following the course of actions below: 1. During the patients initial examination, the presence, size and site of the hyperplasia in the mandibular area were recorded (Fig. 3). 2. The occlusion of the patient’s dentures was corrected by recording the centric relation and performing selective grinding on the articulator. EÈÎ. 2· (¿Óˆ): MË ÙÚÔÔÔÈË̤ÓÔ ÔÚÈÛÙÈÎfi ÂÎÌ·ÁÂ›Ô Ù˘ οو ÁÓ¿ıÔ˘. EÈÎ. 2‚ (οو):TÚÔÔÔÈË̤ÓÔ ÔÚÈÛÙÈÎfi ÂÎÌ·ÁÂ›Ô Ù˘ οو ÁÓ¿ıÔ˘. Fig. 2a (up): Non-modified final cast of the mandible. Fig. 2b (down): Modified final cast of the mandible. Hellenic Stomatological Review 57: 19-26, 2013 £¤Ì· ∫ÏÈÓÈÎÔ‡ ∂ӉȷʤÚÔÓÙÔ˜ Clinical Interest 3. The overextending denture flange was grinded to accommodate the hyperplastic area (Fig. 4). 4. Visco-gel DENTSPLY tissue conditioner was placed on the fitting surface and the denture was placed in the patients mouth and left to set for about 5 min (Fig. 4). 5. The denture was removed, its borders shaped appropriately and excess material was eliminated. 6. The material was replaced over a period of 6 weeks and patient’s progress was recorded. When the hyperplasia was examined again after 6 weeks of conservative treatment20 the initial size of the lesion had been reduced, but not satisfactorily (Fig. 5). The conservative treatment did not have the results expected and it was decided that the lesion would be surgically removed. EÈÎ. 3: KÏÈÓÈ΋ ÂÈÎfiÓ· Ù˘ Ù˘¯ˆÙ‹˜ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜ Ù˘ ·ÛıÂÓÔ‡˜. Fig. 3: Epulis fissuratum - clinical appearance of the patient. Ú·Ê‹ ¤ÁÈÓ Ì ·ÔÚÚÔÊ‹ÛÈÌÔ Ú¿ÌÌ· NÔ 3-0. T· Ú¿ÌÌ·Ù· ‰ÂÓ ‹Ù·Ó ˘fi ȉȷ›ÙÂÚË Ù¿ÛË ÙfiÛÔ ÁÈ· Ó· ÌËÓ ·ÚÂÌÔ‰ÈÛÙ› Ë ÙÔÔı¤ÙËÛË Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ fiÛÔ Î·È Ó· ·ÔÊ¢¯ı› Ë ‰È¿Û·Û‹ ÙÔ˘˜ ·fi ÙÔ ÌÂÙÂÁ¯ÂÈÚËÙÈÎfi Ô›‰ËÌ·. EÈÎ. 5: KÏÈÓÈ΋ ÂÈÎfiÓ· Ù˘ ‚Ï¿‚˘ ÌÂÙ¿ 6 ‚‰ÔÌ¿‰Â˜ Û˘ÓÙËÚËÙÈ΋˜ ıÂڷ›·˜. Fig. 5: Clinical appearance of the lesion after 6 weeks of conservative treatment. EÈÎ. 4: TÔÔı¤ÙËÛË Ù˘ ÙÚÔÔÔÈË̤Ó˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜. Fig. 4: The modified denture in the mouth. 2. M ¤Ó· ‰È·Ê·Ó¤˜ ¯ÂÈÚÔ˘ÚÁÈÎfi ‰ÈÛοÚÈÔ ·fi ·ÎÚ˘ÏÈ΋ ÚËÙ›ÓË, ÈÛÙfi ·ÓÙ›ÁÚ·ÊÔ Ù˘ ‚¿Û˘ Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜23, ÂϤÁ¯ıËÎ·Ó ÔÈ ÈÛÙÔ›, ÁÈ· ÙÔÓ ÂÓÙÔÈÛÌfi ÂÚÈÔ¯ÒÓ Ô˘ Èı·ÓÒ˜ ˘ÂÚȤ˙ÔÓÙ·È ·fi ÙË ‚¿ÛË Ù˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜. ŸÔ˘ ÂÓÙÔ›ÛÙËÎ·Ó ÔÈ ÂÚÈÔ¯¤˜ ·˘Ù¤˜ ¤ÁÈÓÂ Ë ÙÚÔÔÔ›ËÛ‹ ÙÔ˘˜. 3. H ÂÛˆÙÂÚÈ΋ ÂÈÊ¿ÓÂÈ· Ù˘ ÚÔηٷÛ΢·Ṳ̂Ó˘ οو Ô‰ÔÓÙÔÛÙÔȯ›·˜ ÏËÚÒıËΠ̠˘ÏÈÎfi ·ÔηٿÛÙ·Û˘ ÙˆÓ ÈÛÙÒÓ Î·È ÙÔÔıÂÙ‹ıËΠÛÙÔ ÛÙfiÌ· Ù˘ ·ÛıÂÓÔ‡˜ (EÈÎ. 7). 4. H ·ÓÙÈηٿÛÙ·ÛË ÙÔ˘ ˘ÏÈÎÔ‡ ·ÔηٿÛÙ·Û˘ ÙˆÓ ÈÛÙÒÓ ÁÈÓfiÙ·Ó Î¿ı ‚‰ÔÌ¿‰· Î·È Ì¤¯ÚÈ ÙËÓ Ï‹ÚË ÂԇψÛË Ù˘ ¯ÂÈÚÔ˘ÚÁË̤Ó˘ ÂÚÈÔ¯‹˜ (EÈÎ. 8). Hellenic Stomatological Review 57: 19-26, 2013 1. The hyperplasia was removed using a No 15 surgical blade and the material was sent for histological examination (Fig. 6). NÔ 3-0 absorbable sutures were used, which were placed with enough tension to prevent their rupture by post-surgical oedema, yet not too much as to obstruct denture placement. 2. Using a transparent surgical tray, made of acrylic resin23, which was a precise copy of the denture base, the tissues were checked for sites under excessive pressure; such sites were relieved. 3. The fitting surface of the pre-constructed lower denture was filled with tissue conditioner and the denture was placed in the patient’s mouth (Fig. 7). 4. The tissue conditioner was replaced every week until complete healing of the surgically treated area (Fig. 8). DISCUSSION - CONCLUSION Clinical practice has shown that overextended denture flanges cause tissue trauma, which, if this results in longterm irritation, it might lead to the creation of hyperplastic tissue. Hyperplasia is not usually accompanied by pain. If the lesion is painful and if there is also cervical lymphadenopathy present, a clinical picture similar to that of neoplasia4, 19, most patients seek professional help from a dentist. 23 £¤Ì· ∫ÏÈÓÈÎÔ‡ ∂ӉȷʤÚÔÓÙÔ˜ Clinical Interest EÈÎ. 7: H ÚÔηٷÛ΢·Ṳ̂ÓË Ô‰ÔÓÙÔÛÙÔȯ›· Ì ÙÔ ˘ÏÈÎfi ·ÔηٿÛÙ·Û˘ ÙˆÓ ÈÛÙÒÓ. Fig. 7: Fitting surface of the pre-constructed lower denture with tissue conditioner. EÈÎ. 6: XÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË Ù˘ ˘ÂÚÏ·Û›·˜. Fig. 6: Surgical excision of the hyperplasia. ™YZHTH™H - ™YM¶EPA™MATA H ÎÏÈÓÈ΋ Ú¿ÍË ¤¯ÂÈ ‰Â›ÍÂÈ fiÙÈ ˘ÂÚÂÎÙÂٷ̤ӷ ÙÂÚ‡ÁÈ· Ô‰ÔÓÙÔÛÙÔȯ›·˜ ÚÔηÏÔ‡Ó ÙÚ·˘Ì·ÙÈÛÌÔ‡˜ ÙˆÓ ÈÛÙÒÓ ÔÈ ÔÔ›ÔÈ Â›Ó·È ‰˘Ó·ÙfiÓ, Û ̷ÎÚÔ¯ÚfiÓÈÔ ÂÚÂıÈÛÌfi, Ó· ‰ËÌÈÔ˘ÚÁ‹ÛÔ˘Ó ˘ÂÚÏ·ÛÙÈÎfi ÈÛÙfi. ™˘Ó‹ıˆ˜ Ë ˘ÂÚÏ·Û›· ‰ÂÓ Û˘Óԉ‡ÂÙ·È ·fi fiÓÔ. ™ÙȘ ÂÚÈÙÒÛÂȘ Ô˘ Ë ‚Ï¿‚Ë Â›Ó·È ÂÒ‰˘ÓË Î·È, Â¿Ó Û˘Ó˘¿Ú¯ÂÈ ‰ÈfiÁΈÛË ÙˆÓ ÙÚ·¯ËÏÈÎÒÓ ÏÂÌÊ·‰¤ÓˆÓ, ÎÏÈÓÈ΋ ÂÈÎfiÓ· Ô˘ ÚÔÛÔÌÔÈ¿˙ÂÈ Ì ÓÂÔÏ·ÛÌ·ÙÈ΋ ‰ÈÂÚÁ·Û›·4, 19, Ë ÏÂÈÔÓfiÙËÙ· ÙˆÓ ·ÛıÂÓÒÓ ˙ËÙ¿ ÙË ‚Ô‹ıÂÈ· ÙÔ˘ Ô‰ÔÓÙÈ¿ÙÚÔ˘. øÛÙfiÛÔ, ¤Ó· ÌÈÎÚfi ÔÛÔÛÙfi ·ÛıÂÓÒÓ, ·Ó Î·È ·ÓÙÈÌÂÙˆ›˙Ô˘Ó ÂÒ‰˘Ó˜ ÙÚ·˘Ì·ÙÈΤ˜ ηٷÛÙ¿ÛÂȘ ÙˆÓ ÈÛÙÒÓ fiÔ˘ ‰ڿ˙ÂÙ·È Ë Ô‰ÔÓÙÔÛÙÔȯ›·, ›Ù ÏfiÁˆ ·ÓÙÔ¯‹˜ ÛÙÔÓ fiÓÔ, ›Ù ÏfiÁˆ ¿ÁÓÔÈ·˜ ÁÈ· ÙȘ ‚Ï·‚ÂÚ¤˜ Û˘Ó¤ÂȘ (˘ÂÚÏ·Û›·, ·ÔÚÚfiÊËÛË ÙÔ˘ ÔÛÙÔ‡) Ù˘ Û˘Ó¯ԇ˜ ›ÂÛ˘ Î·È ÙÚÈ‚‹˜ ÙÔ˘ ÙÂÚ˘Á›Ô˘ ÛÙÔ˘˜ ˘ÔΛÌÂÓÔ˘˜ ÈÛÙÔ‡˜, Û˘Ó¯›˙Ô˘Ó Ó· ¯ÚËÛÈÌÔÔÈÔ‡Ó ÙȘ ˘ÂÚÂÎÙ·ÙÈΤ˜ ·˘Ù¤˜ Ô‰ÔÓÙÔÛÙÔȯ›Â˜ ÁÈ· Ì·ÎÚ‡ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·13. K¿ÙÈ ·Ó¿ÏÔÁÔ Û˘Ó¤‚Ë Î·È ÛÙËÓ ·ÛıÂÓ‹, Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È ÛÙËÓ ·ÚÔ‡Û· ÂÚÁ·Û›·. H ·ÛıÂÓ‹˜ ·Ó¤ÊÂÚ fiÙÈ «¤¯ÂÈ ÌÂÁ¿ÏË ·ÓÙÔ¯‹ ÛÙÔÓ fiÓÔ» Î·È fiÙÈ «‰ÂÓ ÁÓÒÚÈ˙ ÙÈ ÌÔÚÔ‡Û ӷ Ù˘ ÚÔηϤÛÂÈ Ë ¯Ú‹ÛË Ù˘ ˘ÂÚÂÎÙ·ÙÈ΋˜ Ô‰ÔÓÙÔÛÙÔȯ›·˜». °È’ ·˘Ùfi Î·È fiÙ·Ó ÂÌÊ·Ó›ÛÙËÎ·Ó ÙÚ·‡Ì·Ù· Î·È fiÓÔ˜ ÛÙËÓ Î¿Ùˆ ÁÓ¿ıÔ Ô˘ ¤ÊÂÚ ÙËÓ Ô‰ÔÓÙÔÛÙÔȯ›· Ì ٷ ˘ÂÚÂÎÙ·ÙÈο ÙÂÚ‡ÁÈ·, Ë ·ÛıÂÓ‹˜ ‰ÂÓ ˙‹ÙËÛ ÙË ‚Ô‹ıÂÈ· ÙÔ˘ Ô‰ÔÓÙÈ¿ÙÚÔ˘. ŸÛÔÓ ·ÊÔÚ¿ ÛÙË ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘ Ù˘¯ˆÙ‹˜ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜, Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË ÙÔ˘ ˘ÂÚÏ·ÛÙÈÎÔ‡ ÈÛÙÔ‡, Ô˘ Û ÔÏϤ˜ ÂÚÈÙÒÛÂȘ ÎÚ›ÓÂÙ·È ·Ó·Áη›·, ·ÚÔ˘ÛÈ¿˙ÂÈ ÔÚÈṲ̂ӷ ÌÂÈÔÓÂÎÙ‹Ì·Ù·. 24 EÈÎ. 8: MÂÙÂÁ¯ÂÈÚËÙÈ΋ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÌÂÙ¿ ÙËÓ ¿ÚÔ‰Ô 2 ÌËÓÒÓ. Fig. 8: Post-operative appearance 2 months after surgery. However, a small percentage of patients, despite the painful trauma of the tissues on which the denture is placed, continue to use such overextended dentures for a long period of time, either due to their pain tolerance or because they are not aware of the potential harmful consequences (hyperplasia, bone resorption etc)13. Such was the case of the patient described in this paper. She reported that “she is very tolerant to pain” and that “she did not know what the use of the overextended denture might cause to her”. This is why when the trauma and pain appeared in the mandible on which the denture with the overextended flanges had been placed, the patient did not seek her dental aid. As for the therapeutic treatment of the epulis fissuratum, the surgical excision of the hyperplastic tissue, which is often considered necessary, may cause not only the Hellenic Stomatological Review 57: 19-26, 2013 £¤Ì· ∫ÏÈÓÈÎÔ‡ ∂ӉȷʤÚÔÓÙÔ˜ Clinical Interest EÎÙfi˜ ·fi Ù· ÁÂÓÈο ÚÔ‚Ï‹Ì·Ù· Ô˘ Û˘Ó‹ıˆ˜ ‰ËÌÈÔ˘ÚÁ› ÔÔÈ·‰‹ÔÙ ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË, ÛÙȘ Û˘ÁÎÂÎÚÈ̤Ó˜ ÂÚÈÙÒÛÂȘ Ë ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ Ô˘ÏÈ΋ Û˘ÚÚ›ÎÓˆÛË Èı·ÓfiÓ Ó· ÚÔηϤÛÂÈ Ì›ˆÛË ÙÔ˘ ‚¿ıÔ˘˜ Ù˘ ÚÔÛÙÔÌȷ΋˜ ·‡Ï·Î·˜. H Ì›ˆÛË ·˘Ù‹ ı· ¤¯ÂÈ ·ÚÓËÙÈΤ˜ Û˘Ó¤ÂȘ ÛÙË Û˘ÁÎÚ¿ÙËÛË ÙˆÓ Ô‰ÔÓÙÔÛÙÔȯÈÒÓ. H ÙÔÔı¤ÙËÛË fï˜ Ù˘ ÂȉÈο ÚÔηٷÛ΢·Ṳ̂Ó˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË ÏÂÈÙÔ˘ÚÁ› Û·Ó ¯ÂÈÚÔ˘ÚÁÈÎfi˜ Ó¿ÚıËη˜ ÂÌÔ‰›˙ÔÓÙ·˜ ÙËÓ Ô˘ÏÒ‰Ë Ú›ÎÓˆÛË ÙˆÓ ÈÛÙÒÓ Î·È ÙË Ì›ˆÛË ÙÔ˘ ‚¿ıÔ˘˜ Ù˘ ·‡Ï·Î·˜. H ¯Ú‹ÛË ÙˆÓ laser ·ÚÔ˘ÛÈ¿˙ÂÈ ·ÚÎÂÙ¿ ÏÂÔÓÂÎÙ‹Ì·Ù· fiˆ˜ ÂÏ¿¯ÈÛÙË ·ÈÌÔÚÚ·Á›·, ÌÂȈ̤ÓÔ Ô›‰ËÌ· Ù˘ ÂÚÈÔ¯‹˜, ÏÈÁfiÙÂÚÔ fiÓÔ Î·È ‰ÂÓ Â›Ó·È ··Ú·›ÙËÙË Ë ¯Ú‹ÛË Ú·ÌÌ¿ÙˆÓ24-27. ¶·ÚfiÏ· ·˘Ù¿, ÂÓÒ Û˘ÁÎÚÈÙÈο Ì ÙËÓ ÎÏ·ÛÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋ Ô ÈÛÙfi˜ ·ÚÔ˘ÛÈ¿˙ÂÈ ÌÈÎÚ‹ ÌÂÙ·ÙÚ·˘Ì·ÙÈ΋ Û˘ÚÚ›ÎÓˆÛË, Ë ¯ÂÈÚÔ˘ÚÁÈ΋ Ì laser ÂÌÊ·Ó›˙ÂÈ ÈÔ ·ÚÁ‹ ·Ú¯È΋ ÂԇψÛË, Û¯ËÌ·ÙÈÛÌfi ÏÈÁfiÙÂÚÔ˘ ÎÔÏÏ·ÁfiÓÔ˘ Î·È Ë ·Ó·Á¤ÓÓËÛË ÙÔ˘ ÂÈıËÏ›Ô˘ Á›ÓÂÙ·È ·ÚÁ¿ Î·È ·Î·ÓfiÓÈÛÙ·24, 27. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ¿ÌÂÛË ÙÔÔı¤ÙËÛË Ù˘ ÂȉÈο ÚÔηٷÛ΢·Ṳ̂Ó˘ Ô‰ÔÓÙÔÛÙÔȯ›·˜ ÛÙÔ ÛÙfiÌ· ÙÔ˘ ·ÛıÂÓÔ‡˜, ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË Ù˘ Ù˘¯ˆÙ‹˜ ÈÓÒ‰Ô˘˜ ˘ÂÚÏ·Û›·˜ ·fi Ô‰ÔÓÙÔÛÙÔȯ›·, Ì ÙËÓ ÎÏ·ÛÛÈ΋ Ù¯ÓÈ΋, ÂÌÔ‰›˙ÂÈ ÙËÓ Ô˘ÏÒ‰Ë Û˘ÚÚ›ÎÓˆÛË ÙˆÓ ÈÛÙÒÓ Î·È Î·Ù’ ¤ÎÙ·ÛË ÙË Ì›ˆÛË Ù˘ ÚÔÛÙÔÌȷ΋˜ ·‡Ï·Î·˜ ÛÙË Û˘ÁÎÂÎÚÈ̤ÓË ÂÚÈÔ¯‹. O Ô‰ÔÓÙ›·ÙÚÔ˜ ı· Ú¤ÂÈ Ó· ·Ú·ÎÔÏÔ˘ı› Û ٷÎÙ¿ ¯ÚÔÓÈο ‰È·ÛÙ‹Ì·Ù· ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÊÔÚÔ‡Ó Ô‰ÔÓÙÔÛÙÔȯ›Â˜ ÒÛÙÂ, ·ÚÂÌ‚·›ÓÔÓÙ·˜ ηٿÏÏËÏ·, Ó· ÚÔÏ·Ì‚¿ÓÔÓÙ·È ‰˘Û¿ÚÂÛÙ˜ ηٷÛÙ¿ÛÂȘ (˘ÂÚϷۛ˜, ·ÔÚÚfiÊËÛË ÙÔ˘ ˘ÔΛÌÂÓÔ˘ ÔÛÙÔ‡ Î.¿.) ÛÙ· ·Ú¯Èο ÛÙ¿‰È·. BIB§IO°PAºIA 1. §¿ÛηÚ˘ °X: ŒÁ¯ÚˆÌÔ˜ ÕÙÏ·˜ ™ÙÔÌ·ÙÔÏÔÁ›·˜. Aı‹Ó·. I·ÙÚÈΤ˜ EΉfiÛÂȘ §›ÙÛ·˜. 1986: 56. 2. Grant AA, Heath JR, McCord JF: Complete Prosthodontics: Problems, Diagnosis, and Management. Spain. Wolfe Publ 1994: 36. 3. Ogle RE: Preprosthetic surgery. Dent Clin North Am 1977; 21 (2): 219-236. 4. Budtz-J∅ rgensen E: Sequelae Caused by Wearing Complete Dentures. In: Zarb GA, Bolender CL. Prosthodontic Treatment for Edentulous Patients. Complete Dentures and Implant - Supported Prostheses. 12th ed. St. Louis. Mosby 2004: 40. 5. Carlsson GE: Clinical morbidity and sequelae of treatment with complete dentures. J Prosthet Dent 1997; 79 (1): 17-23. 6. Coelho CMP, Sousa YTCS, Daré AMZ: Denture-related oral mucosal lesions in a Brazilian school of dentistry. J Oral Rehabil 2004(2); 31: 135-139. 7. Freitas JB, Gomez RS, De Abreu MHNG, Ferreira E, Ferreira E: Relationship between the use of full dentures and mucosal alterations among elderly Brazilians. J Oral Rehabil 2008; 35 (5): 370-374. 8. Bilhan H, Geckili O, Ergin S, Erdogan O, Ates G: Evaluation of satisfaction and complications in patients with existing complete dentures. J Oral Sci 2013; 55 (1): 29-37. 9. Xie Q, Närhi TO, Nevalainen JM, Wolf J, Ainamo A: Oral status and prosthetic factors related to residual ridge resorption in Hellenic Stomatological Review 57: 19-26, 2013 general problems any surgery may cause, but, in these specific cases, it may also lead to post-operative scar formation and tissue shrinkage, which results in loss of vestibular sulcus depth. This in turn will have a negative effect on denture retention. Nevertheless, if specially constructed dentures are placed in the mouth directly after the surgical intervention, they function like a surgical splint and prevent scar formation and tissue shrinkage, while maintaining the depth of the vestibular sulcus. The use of laser presents several advantages, such as minimal haemorrhage, reduced local oedema, less pain and no need for using sutures24-27. Yet, although the tissue presents smaller post-traumatic shrinkage compared to conventional surgery, initial healing following laser surgery is slower, less collagen is formed and the epithelium is regenerated slowly and irregularly24, 27. In conclusion, it may be said that placing a specially constructed denture in the patient’s mouth, directly after the surgical excision of epulis fissuratum caused by dentures, prevents scar formation and tissue shrinkage and, therefore, maintains the depth of the vestibular sulcus in the affected region. A dentist should regularly examine patients, who wear dentures, so as to promptly intervene and prevent unpleasant sequelae (hyperplasia, bone resorption, etc) at early stages. BIB§IO°PAºIA 1. Laskaris GCh: Coloured Atlas of Stomatology. Athens. Medical Publications. Litsas 1986: 56. 2. Grant AA, Heath JR, McCord JF: Complete Prosthodontics: Problems, Diagnosis, and Management. Spain. Wolfe Publ 1994: 36. 3. Ogle RE: Preprosthetic surgery. Dent Clin North Am 1977; 21 (2): 219-236. 4. Budtz-J∅ rgensen E: Sequelae Caused by Wearing Complete Dentures. In: Zarb GA, Bolender CL. Prosthodontic Treatment for Edentulous Patients. Complete Dentures and Implant - Supported Prostheses. 12th ed. St. Louis. Mosby 2004: 40. 5. Carlsson GE: Clinical morbidity and sequelae of treatment with complete dentures. J Prosthet Dent 1997; 79 (1): 17-23. 6. Coelho CMP, Sousa YTCS, Daré AMZ: Denture-related oral mucosal lesions in a Brazilian school of dentistry. J Oral Rehabil 2004(2); 31:135-139. 7. Freitas JB, Gomez RS, De Abreu MHNG, Ferreira E, Ferreira E: Relationship between the use of full dentures and mucosal alterations among elderly Brazilians. J Oral Rehabil 2008; 35 (5): 370-374. 8. Bilhan H, Geckili O, Ergin S, Erdogan O, Ates G: Evaluation of satisfaction and complications in patients with existing complete dentures. J Oral Sci 2013; 55 (1): 29-37. 9. Xie Q, Närhi TO, Nevalainen JM, Wolf J, Ainamo A: Oral status and prosthetic factors related to residual ridge resorption in elderly subjects. Acta Odontol Scand 1997; 55 (5): 306-313. 10. Canger EM, Celenk P, Kayipmaz S: Denture-related hyperplasia: A clinical study of a Turkish population group. Braz Dent J 2009; 20 (3): 243-248. 11. Hobkirk JA: Complete dentures. Bristol. Wright. 1986: 11, 26. 25 £¤Ì· ∫ÏÈÓÈÎÔ‡ ∂ӉȷʤÚÔÓÙÔ˜ Clinical Interest elderly subjects. Acta Odontol Scand 1997; 55 (5): 306-313. 10. Canger EM, Celenk P, Kayipmaz S: Denture-related hyperplasia: A clinical study of a Turkish population group. Braz Dent J 2009; 20 (3): 243-248. 11. Hobkirk JA: Complete dentures. Bristol. Wright 1986: 11, 26. 12. BÏËÛ›‰Ë˜ ¢™: O‰ÔÓÙÔÚÔÛıÂÙÈ΋ III. Aı‹Ó·. I·ÙÚÈΤ˜ EΉfiÛÂȘ ¶·Û¯·Ï›‰Ë˜ 1987: 88. 13. Basker RM, Davenport JC, Tomlin HR: Prosthetic treatment of the edentulous patient. 3rd ed. London. Macmillan Press LTD 1992: 131, 132. 14. Winkler S: Essentials of complete denture prosthodontics. 2nd ed. St. Louis - Tokyo. Ishiyaku EuroAmerica, Inc Publishers 1994: 47, 48. 15. ºÚ·ÁΛÛÎÔ˜ º: XÂÈÚÔ˘ÚÁÈ΋ ÛÙfiÌ·ÙÔ˜. Aı‹Ó· 2000: 33640. 16. AÁÁÂÏfiÔ˘ÏÔ˜ A¶, AÏÂÍ·Ó‰Ú›‰Ë˜ KA, K·ÙÛÈΤÚ˘ Nº: ™‡Á¯ÚÔÓË ™ÙÔÌ·ÙÈ΋ XÂÈÚÔ˘ÚÁÈ΋. 2Ë ÂΉ. Aı‹Ó· 2008: 414-17. 17. M¿ÚÙ˘ X: ™ÙÔÌ·ÙÔÁÓ·ıÔÚÔÛˆÈ΋ XÂÈÚÔ˘ÚÁÈ΋. Aı‹Ó·. EΉfiÛÂȘ «ZHTA» 1996: 1469. 18. Thomas GA: Denture - induced fibrous inflammatory hyperplasia (epulis fissuratum): research aspects. Aust Prosthodont J 1993; 7: 49-53. 19. McCord JF, Grant AA: A clinical guide to complete denture prosthetics. London. British Dental Association 2000: 11. 20. ¢ËÌËÙÚ›Ô˘ ¶, Z‹Û˘ A, K·Úη˙‹˜ H, ¶ÔÏ˘˙Ò˘ °, ™Ù·˘Ú¿Î˘ °: KÈÓËÙ‹ ¶ÚÔÛıÂÙÈ΋. OÏÈΤ˜ Ô‰ÔÓÙÔÛÙÔȯ›Â˜. 4Ë ÂΉ. Aı‹Ó·. M. MÔÓÈÛ¤Ï 2001: 185-187. 21. Is,eri U, Ozc,akir-Tomruk C, Gürsoy-Mert H: Treatment of epulis fissuratum with CO2 laser and prosthetic rehabilitation in patients with vesiculobullous disease. Photomed Laser Surg 2009; 27 (4): 675-681. 22. Monteiro LS, Mouzinho J, Azevedo A, da Camara MI, Martins MA, La Fuente JM: Treatment of epulis fissuratum with carbon dioxide laser in a patient with antithrombotic medication. Braz Dent J 2012; 23 (1): 77-81. 23. OÈÎÔÓfiÌÔ˘ ¶N: ÕÌÂÛ˜ ÔÏÈΤ˜ Ô‰ÔÓÙÔÛÙÔȯ›Â˜. 2Ë ÂΉ. Aı‹Ó·. O‰ÔÓÙÈ·ÙÚÈΤ˜ EΉfiÛÂȘ ™. Z·¯·ÚfiÔ˘ÏÔ˜ 2004: 93. 24. Fisher SE, Frame JW, Browne RM, Tranter RMD: A comparative histological study of wound healing following CO2 laser and conventional surgical excision of canine buccal mucosa. Arch Oral Biol 1983; 28 (4): 287-291. 25. Nammour S, Romanos G: Lasers in oral surgery and implant dentistry. In: Proceedings of the 1st International Workshop of Evidence Based Dentistry. Quintessence Publishing Co. Ltd. 2007: 129-147. 26. Kafas P, Upile T, Stavrianos C, Angouridakis N, Jerjes W: Mucogingival overgrowth in a geriatric patient. Dermatol Online J 2010; 16 (8): 7. 27. de Arruda Paes-Junior TJ, Cavalcanti SCM, Nascimento DFF, de Siqueira Ferreira Anzaloni Saavedra G, Kimpara ET, Borges ALS, Niccoli-Filho W, de Paiva Komori PC: CO2 Laser Surgery and Prosthetic Management for the Treatment of Epulis Fissuratum. ISRN Dentistry 2011; 2011: 282361. doi: 10.5402/2011/282361. Epub 2010 Nov 28, 5pp. 12. Vlisidis DS: Dental Prosthetics III. Athens. Medical Publications. Paschalidis 1987: 88. 13. Basker RM, Davenport JC, Tomlin HR: Prosthetic treatment of the edentulous patient. 3rd ed. London. Macmillan Press LTD. 1992: 131,132. 14. Winkler S: Essentials of complete denture prosthodontics. 2nd ed. St. Louis - Tokyo. Ishiyaku EuroAmerica, Inc. Publishers 1994: 47, 48. 15. Fragiskos F: Oral surgery. Athens 2000: 336-40. 16. Angelopoulos AP, Alexandridis CA, Katsikeris NF: Modern Oral Surgery. 2nd ed. Athens. 2008: 414-17. 17. Martis ChS: Oral and Maxillofacial Surgery. Athens. “ZHTA” Publications 1996: 1469. 18. Thomas GA: Denture - induced fibrous inflammatory hyperplasia (epulis fissuratum): research aspects. Aust Prosthodont J 1993; 7: 49-53. 19. McCord JF, Grant AA: A clinical guide to complete denture prosthetics. London. British Dental Association 2000: 11. 20. Dimitriou P, Zissis A, Karkazis H, Polyzois G, Stavrakis G: Removable Prosthodontics. Complete dentures. 4nd ed. Athens. M Bonisel 2001: 185-187. 21. Is,eri U, Ozc,akir-Tomruk C, Gürsoy-Mert H: Treatment of epulis fissuratum with CO2 laser and prosthetic rehabilitation in patients with vesiculobullous disease. Photomed Laser Surg 2009; 27 (4): 675-681. 22. Monteiro LS, Mouzinho J, Azevedo A, da Camara MI, Martins MA, La Fuente JM: Treatment of epulis fissuratum with carbon dioxide laser in a patient with antithrombotic medication. Braz Dent J 2012; 23 (1): 77-81. 23. Economou PN: Immediate complete dentures. 2nd ed. Athens. Dental Publicatons. S Zacharopoulos 2004: 93. 24. Fisher SE, Frame JW, Browne RM, Tranter RMD: A comparative histological study of wound healing following CO2 laser and conventional surgical excision of canine buccal mucosa. Arch Oral Biol 1983; 28 (4): 287-291. 25. Nammour S, Romanos G: Lasers in oral surgery and implant dentistry. In: Proceedings of the 1st International Workshop of Evidence Based Dentistry. Quintessence Publishing Co. Ltd. 2007: 129-147. 26. Kafas P, Upile T, Stavrianos C, Angouridakis N, Jerjes W: Mucogingival overgrowth in a geriatric patient. Dermatol Online J 2010; 16 (8): 7. 27. de Arruda Paes-Junior TJ, Cavalcanti SCM, Nascimento DFF, de Siqueira Ferreira Anzaloni Saavedra G, Kimpara ET, Borges ALS, Niccoli-Filho W, de Paiva Komori PC: CO2 Laser Surgery and Prosthetic Management for the Treatment of Epulis Fissuratum. ISRN Dentistry 2011; 2011: 282361. doi: 10.5402/2011/282361. Epub 2010 Nov 28, 5pp. Contact details: ªichael Sotiriou e-mail: [email protected] ¢È‡ı˘ÓÛË ÁÈ· ÂÈÎÔÈÓˆÓ›·: ªÈ¯¿Ï˘ ™ˆÙËÚ›Ô˘ e-mail: [email protected] 26 Hellenic Stomatological Review 57: 19-26, 2013 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review ∏ ¢È·Ù·ÙÈ΋ OÛÙÂÔÁ¤ÓÂÛË ÛÙËÓ ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋. ¶·ÚÔ˘Û›·ÛË ÂÚ›ÙˆÛ˘ Î·È ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜ Ã. ™Ô˘Ï›Ô˘*, ∞. ∑·‹*, °. μ·Á‰Ô‡ÙË*, º. Δ˙¤ÚÌÔ˜** The Distraction Osteogenesis in pre-implant surgery. A case report and review of the literature C. Souliou*, C. Zappi*, G. Bagdouti*, F. Tzermpos** ¶EPI§HæH SUMMARY H ¢È·Ù·ÙÈ΋ OÛÙÂÔÁ¤ÓÂÛË (¢O) ·ÔÙÂÏ› ÌÈ· ÌÔÓ·‰È΋ ̤ıÔ‰Ô Û¯ËÌ·ÙÈÛÌÔ‡ Ó¤Ô˘ ÔÛÙÔ‡ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙËÓ ÂÔ˘ÏˆÙÈ΋ ÈηÓfiÙËÙ· ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡. EÈÙ˘Á¯¿ÓÂÙ·È Ì ÔÛÙÂÔÙÔÌ›· ÙÔ˘ ÚÔ˜ ÂÈÌ‹Î˘ÓÛË ÔÛÙÔ‡ Î·È ÙËÓ ÂÊ·ÚÌÔÁ‹ ‰È·Ù·ÙÈÎÒÓ ‰˘Ó¿ÌÂˆÓ Âη٤ڈıÂÓ Ù˘ ÔÛÙÂÔÙÔÌ›·˜ ·fi ÂȉÈ΋ Û˘Û΢‹. H ‰È¿Ù·ÛË, Ë ÔÔ›· ÂÊ·ÚÌfi˙ÂÙ·È, Ô‰ËÁ› ÛÙË ‰ËÌÈÔ˘ÚÁ›· Ó¤Ô˘ ÔÛÙÔ‡ ·Ó¿ÌÂÛ· ÛÙ· ÔÛÙÈο ¿ÎÚ·, ·Ú¿ÏÏËÏ· ÚÔ˜ ÙË ÊÔÚ¿ Ù˘ ÂÊ·ÚÌÔ˙fiÌÂÓ˘ ‰‡Ó·Ì˘. H ¢O ÂÊ·ÚÌfiÛÙËΠ·Ú¯Èο ·fi oÚıÔ‰ÈÎÔ‡˜ ÁÈ· ÙËÓ ÂÈÌ‹Î˘ÓÛË Ì·ÎÚÒÓ ÔÛÙÒÓ. H Ù¯ÓÈ΋ Ù˘ ‰È·Ù·ÙÈ΋˜ ÔÛÙÂÔÁ¤ÓÂÛ˘ ÂÊ·ÚÌfiÛÙËΠÛÙËÓ ÎÚ·ÓÈÔÁÓ·ıÔÚÔÛˆÈ΋ ÂÚÈÔ¯‹ Û ÔÈΛϘ ÂÚÈÙÒÛÂȘ Û˘ÁÁÂÓÒÓ ‹ ÂÈÎÙ‹ÙˆÓ ÔÛÙÈÎÒÓ ÂÏÏÂÈÌÌ¿ÙˆÓ Ì ÛÙfi¯Ô ÙËÓ ·‡ÍËÛË ÙÔ˘ ÔÛÙÔ‡. TÔ Î˘ÚÈfiÙÂÚÔ ÏÂÔÓ¤ÎÙËÌ· Ù˘ ¢O ÂÎÙfi˜ ·fi ÙËÓ ÔÈÔÙÈ΋ ·Ó¿Ï·ÛË ÙÔ˘ ÔÛÙÈÎÔ‡ ˘ÔÛÙÚÒÌ·ÙÔ˜ Â›Ó·È Î·È Ë Ù·˘Ùfi¯ÚÔÓË ·Ó¿Ï·ÛË ÙˆÓ Ì·Ï·ÎÒÓ ÈÛÙÒÓ. M ˘„ËÏ¿ ÔÛÔÛÙ¿ ÂÈ- Distraction osteogenesis (DO) is a unique method of new bone formation using body’s healing ability. DO can be achieved with osteotomy of the bone and the application of distraction forces to either side of the osteotomy by a special distraction device. The applied distraction leads to new bone formation between the bone segments in the direction of the force. DO was initially used by orthopedists for elongation of long bones. The procedure of distraction osteogenesis is applied in the craniomaxillofacial region in various cases of congenital or acquired bone defects, aimed bone augmentation. The main advantage of DO, apart from bone regeneration, is the simultaneous regeneration of soft tissues. High success rates are also indicated in pre-implant surgery. For achieving these outcomes, a special surgical experience and absolute patient’s cooperation is required. The purpose of * O‰ÔÓÙ›·ÙÚÔ˜ ** ∂›Î. ∫·ıËÁËÙ‹˜ ™ÙÔÌ·ÙÈ΋˜ Î·È °Ó·ıÔÚÔÛˆÈ΋˜ ÃÂÈÚÔ˘ÚÁÈ΋˜ O‰ÔÓÙÈ·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ∂∫¶∞ ∫ÏÈÓÈ΋ ™ÙÔÌ·ÙÈ΋˜ Î·È °Ó·ıÔÚÔÛˆÈ΋˜ ÃÂÈÚÔ˘ÚÁÈ΋˜ O‰ÔÓÙÈ·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ∂∫¶∞ ÂÏÏËÓÈο ÛÙÔÌ·ÙÔÏÔÁÈο ¯ÚÔÓÈο 57: 27-37, 2013 ·ÚÂÏ‹ÊıË 10/6/2013 - ÂÎÚ›ıË 5/7/2013 * Dentist ** Assistant Professor of Oral and Maxillofacial Surgery, National and Kapodistrian University of Athens, School of Dentistry Oral and Maxillofacial Clinic, National and Kapodistrian University of Athens, School of Dentristry Hellenic Stomatological Review 57: 27-37, 2013 paper received 10/6/2013 - accepted 5/7/2013 27 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review Ù˘¯›·˜ ÂÊ·ÚÌfi˙ÂÙ·È Î·È ÛÙËÓ ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋. °È· ÙËÓ Â›Ù¢ÍË ·˘ÙÒÓ ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ··ÈÙÂ›Ù·È È‰È·›ÙÂÚË ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÌÂÈÚ›· Î·È ·fiÏ˘ÙË Û˘ÓÂÚÁ·Û›· ÙÔ˘ ·ÛıÂÓÔ‡˜. ™ÎÔfi˜ ·˘Ù‹˜ Ù˘ ÂÚÁ·Û›·˜ Â›Ó·È Ë ·ÚÔ˘Û›·ÛË ÌÈ¿˜ ÂÚ›ÙˆÛ˘ ÂÊ·ÚÌÔÁ‹˜ Ù˘ ¢O ÛÙËÓ Î¿Ùˆ ÁÓ¿ıÔ ·ÛıÂÓÔ‡˜. °›ÓÂÙ·È ÂÚÈÁÚ·Ê‹ Ù˘ Ù¯ÓÈ΋˜, ÙˆÓ ÏÂÔÓÂÎÙËÌ¿ÙˆÓ Î·È ÌÂÈÔÓÂÎÙËÌ¿ÙˆÓ Î·ıÒ˜ Î·È ÙˆÓ Èı·ÓÒÓ ÂÈÏÔÎÒÓ. T¤ÏÔ˜ Á›ÓÂÙ·È Û˘ÁÎÚÈÙÈ΋ ‚È‚ÏÈÔÁÚ·ÊÈ΋ ÌÂϤÙË Ù˘ ¢O Û ۯ¤ÛË Ì ٷ ÔÛÙÈο ·˘ÙÔÌÔۯ‡̷ٷ ÛÙ· Ï·›ÛÈ· Ù˘ ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋˜ ¯ÂÈÚÔ˘ÚÁÈ΋˜. §¤ÍÂȘ ÎÏÂȉȿ: ‰È·Ù·ÙÈ΋ ÔÛÙÂÔÁ¤ÓÂÛË, ÂÌÊ˘Ù‡̷ٷ, ÔÛÙÈο ÌÔۯ‡̷ٷ, ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋. EI™A°ø°H ™‹ÌÂÚ· ÙÔ ·ÁÎfiÛÌÈÔ ÂӉȷʤÚÔÓ ÛÙÚ¤ÊÂÙ·È ÛÙËÓ ·Ó¿Ù˘ÍË ÌÂıfi‰ˆÓ ÂÏ¿¯ÈÛÙ˘ ÂÂÌ‚·ÙÈ΋˜ ¯ÂÈÚÔ˘ÚÁÈ΋˜. T¤ÙÔÈÔ˘ ›‰Ô˘˜ ̤ıÔ‰Ô˜ Â›Ó·È Î·È Ë ‰È·Ù·ÙÈ΋ ÔÛÙÂÔÁ¤ÓÂÛË. H ¢È·Ù·ÙÈ΋ OÛÙÂÔÁ¤ÓÂÛË (¢O) ·ÔÙÂÏ› ÌÈ· ÌÔÓ·‰È΋ ̤ıÔ‰Ô ·‡ÍËÛ˘ ÙˆÓ ‰È·ÛÙ¿ÛÂˆÓ ÙÔ˘ ÔÛÙÔ‡ Ì ۯËÌ·ÙÈÛÌfi Ó¤Ô˘ ÔÛÙÔ‡ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙËÓ ÂÔ˘ÏˆÙÈ΋ ÈηÓfiÙËÙ· ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡. EÈÙ˘Á¯¿ÓÂÙ·È Ì ÔÛÙÂÔÙÔÌ›· ÙÔ˘ ÚÔ˜ ·‡ÍËÛË ÔÛÙÔ‡ Î·È ÙËÓ ÂÊ·ÚÌÔÁ‹ ‰È·Ù·ÙÈÎÒÓ ‰˘Ó¿ÌÂˆÓ Âη٤ڈıÂÓ Ù˘ ÔÛÙÂÔÙÔÌ›·˜ ·fi ÂȉÈ΋ Û˘Û΢‹. MÂٷ͇ ÙˆÓ ÔÛÙÈÎÒÓ ÙÂÌ·¯›ˆÓ ‰ËÌÈÔ˘ÚÁÂ›Ù·È ÒÚÔ˜, Ô ÔÔ›Ô˜ ÛÙ·‰È·Î¿ ‰È·Ù›ÓÂÙ·È Ì ÙËÓ ÂÓÂÚÁÔÔ›ËÛË Ù˘ ‰È·Ù·ÙÈ΋˜ Û˘Û΢‹˜ Î·È ÙËÓ ·ÔÌ¿ÎÚ˘ÓÛË ÙˆÓ ÔÛÙÈÎÒÓ ÙÌËÌ¿ÙˆÓ ÌÂٷ͇ ÙÔ˘˜. H ‰È¿Ù·ÛË ·˘Ù‹ Ô‰ËÁ› ÛÙË ‰ËÌÈÔ˘ÚÁ›· Ó¤Ô˘ ÔÛÙÔ‡ ·Ó¿ÌÂÛ· ÛÙ· ÔÛÙÈο ÙÂÌ¿¯È·, ·Ú¿ÏÏËÏ· ÚÔ˜ ÙË ÊÔÚ¿ Ù˘ ÂÊ·ÚÌÔ˙fiÌÂÓ˘ ‰‡Ó·Ì˘1. H ¢O ÂÊ·ÚÌfiÛÙËΠ·Ú¯Èο ·fi oÚıÔ‰ÈÎÔ‡˜ ÁÈ· ÙËÓ ÂÈÌ‹Î˘ÓÛË Ì·ÎÚÒÓ ÔÛÙÒÓ2. TÔ 1905, Ô A. Codivilla ÂÚȤÁÚ·„ ÁÈ· ÚÒÙË ÊÔÚ¿, ÂÚ›ÙˆÛË ÂÈÌ‹Î˘ÓÛ˘ ÌËÚÈ·›Ô˘ ÔÛÙÔ‡ Ì ¢O. ø˜ ·Ù¤Ú·˜ Ù˘ ¢O ıˆÚÂ›Ù·È Ô Illizarov, Ô ÔÔ›Ô˜ ÙË ‰ÂηÂÙ›· ÙÔ˘ 1950 ·ÚÔ˘Û›·Û ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ Û ÌÂÁ¿ÏÔ ·ÚÈıÌfi ·ÛıÂÓÒÓ, ‰ËÌÔÛ›Â˘Û ٷ ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÂÈÚ·Ì·ÙÈÎÒÓ ÌÂÏÂÙÒÓ ÙÔ˘ Û ÂÈÚ·Ì·Ùfi˙ˆ· Î·È Î·ıfiÚÈÛ ÙȘ ‚·ÛÈΤ˜ ·Ú¯¤˜ Ù˘ ¢O3. H Ù¯ÓÈ΋ Ù˘ ¢O ‚Ú›ÛÎÂÈ ÔÈΛϘ ÂÊ·ÚÌÔÁ¤˜ ÛÙË ÁÓ·ıÔÚÔÛˆÈ΋ ÂÚÈÔ¯‹ Î·È ·Ó¿ÌÂÛ· Û ·˘Ù¤˜ Û˘ÁηٷϤÁÂÙ·È Ë ·‡ÍËÛË ÙˆÓ ‰È·ÛÙ¿ÛÂˆÓ ÙÔ˘ ÔÛÙÈÎÔ‡ ˘ÔÛÙÚÒÌ·ÙÔ˜ ÛÙ· Ï·›ÛÈ· Ù˘ ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋˜ ¯ÂÈÚÔ˘ÚÁÈ΋˜. ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÂÚÁ·Û›·˜ Â›Ó·È Ë ·ÚÔ˘Û›·ÛË ÌÈ·˜ ÎÏÈÓÈ΋˜ ÂÚ›ÙˆÛ˘ ·ÛıÂÓÔ‡˜ 22 ÂÙÒÓ Ô˘ ˘Ô‚Ï‹ıËΠ۠¢O Ù˘ ÚfiÛıÈ·˜ ÂÚÈÔ¯‹˜ Ù˘ οو ÁÓ¿ıÔ˘ Ì ÛÙfi¯Ô ÙËÓ ÂÈÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ·ÔηٿÛÙ·ÛË. ¶APOY™IA™H ¶EPI™TATIKOY ÕÓ‰Ú·˜ ËÏÈΛ·˜ 22 ÂÙÒÓ ·Ú¤ÌÊıË ÁÈ· ·ÔηٿÛÙ·28 this article is to present a clinical case, where DO was applied in the anterior region of the a patient’s mandible. The procedure as well as its indications, advantages and disadvantages are described additionally to the method’s complications. Finally, a literature review is also presented comparing DO to bone grafts within the area of pre-implant surgery. Key Words: distraction osteogenesis, implants, bone grafts, pre-implant surgery. INTRODUCTION Nowadays the worldwide interest is turning in developing methods for minimally invasive surgery. Such a method is distraction osteogenesis. Distraction osteogenesis (DO) stands as a unique method of new bone formation using body’s healing ability. This is achieved with osteotomy of the bone in augmentation need and the application of distracting forces on the two sides of the osteotomy from a special device. Between the bone segments, an initial callus is created, which is gradually distracted with the activation of the device and the separation of the segments. This way osteogenesis is created between the bone segments towards the direction of the power stress1. DO was initially used by orthopedists for the elongation of the long bones2. In 1905, A. Codvilla described for the first time a case of femur lengthening with DO. Father of this procedure is considered to be Illizarov who used the technique among a great amount of patients in the 1950s. He published his experimental research outcomes and he introduced the basic principles of DO3. DO procedures meets a variety of applications in maxillofacial region which include augmentation of deficient ridges in preprosthetic surgery. This paper’s purpose is to present a clinical case of a 22 year old male patient who underwent a DO procedure in the anterior area of his mandible for implant supported restoration. CASE PRESENTATION A 22 years old male patient was referred for the restoration of the partial edentulous area of his anterior mandible. The patient reported that at the age of 13 he was involved in a motor vehicle accident resulting to a fracture of the mandible in the area of symphysis and loss of eight teeth from the lower left second premolar up to lower right canine (35 to 43). The treatment at that time was open reduction with internal fixation using two osteosynthesis plates. Since then the patient carried a partial denture. His medical history was not contributory for any disease, he was not taking drugs systematically or mentioned any allergies and he was not a smoker. The clinical and radiographic findings (Fig. 1, 2) showed the Hellenic Stomatological Review 57: 27-37, 2013 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review ÛË ÂÎÙÂٷ̤Ó˘ ÌÂÚÈ΋˜ ·ÓÔ‰ÔÓÙ›·˜ ÛÙËÓ ÚfiÛıÈ· ÂÚÈÔ¯‹ Ù˘ οو ÁÓ¿ıÔ˘. O ·ÛıÂÓ‹˜ Û ËÏÈΛ· 13 ÂÙÒÓ ˘‹ÚÍ ı‡Ì· ·˘ÙÔÎÈÓËÙÈÛÙÈÎÔ‡ ·Ù˘¯‹Ì·ÙÔ˜ ÌÂ Û˘Ó¤ÂÈ· οٷÁÌ· ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ Û‡ÌÊ˘Û˘ Ù˘ οو ÁÓ¿ıÔ˘, ÁÈ· ÙÔ ÔÔ›Ô ˘Â‚Ï‹ıË Û ·ÓÔÈÎÙ‹ ·Ó¿Ù·ÍË Î·È ·ÎÈÓËÙÔÔ›ËÛË Ì ‰‡Ô ϿΘ ÔÛÙÂÔÛ‡ÓıÂÛ˘ Î·È ·ÒÏÂÈ· Û˘ÓÔÏÈο ÔÎÙÒ ‰ÔÓÙÈÒÓ ÛÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÂÚÈÔ¯‹ Ù˘ οو ÁÓ¿ıÔ˘ Î·È Û˘ÁÎÂÎÚÈ̤ӷ ·fi ÙÔ 35 ̤¯ÚÈ Î·È ÙÔ 43. ŒÎÙÔÙÂ Ô ·ÛıÂÓ‹˜ ¤ÊÂÚ ÌÂÚÈ΋ Ô‰ÔÓÙÔÛÙÔȯ›·. TÔ È·ÙÚÈÎfi ÈÛÙÔÚÈÎfi ‰ÂÓ ‹Ù·Ó ÛËÌ·ÓÙÈÎfi ÁÈ· οÔÈ· ·Ûı¤ÓÂÈ·, ‰ÂÓ ¤·ÈÚÓ ʿÚ̷η Û˘ÛÙËÌ·ÙÈο, ‰ÂÓ ·Ó¤ÊÂÚ ·ÏÏÂÚÁ›Â˜ Î·È ‰ÂÓ Î¿ÓÈ˙Â. Afi ÙËÓ ÎÏÈÓÈ΋ Î·È ·ÎÙÈÓÔÁÚ·ÊÈ΋ ÂͤٷÛË (EÈÎ. 1, 2) ‰È·ÈÛÙÒıËÎÂ Ë ‡·ÚÍË ÙˆÓ ‰‡Ô Ï·ÎÒÓ ÔÛÙÂÔÛ‡ÓıÂÛ˘ Î·È ÂÎÙÂٷ̤ÓÔ ¤ÏÏÂÈÌÌ· ÙÔ˘ ÔÛÙÈÎÔ‡ ˘ÔÛÙÚÒÌ·ÙÔ˜, ÙÔ ÔÔ›Ô ·fi ÙËÓ ÂÚÁ·ÛÙËÚȷ΋ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÌÂϤÙË ˘ÔÏÔÁ›ÛÙËΠ۠12 mm ÛÙÔ Î¿ıÂÙÔ Â›Â‰Ô (ηı’ ‡„Ô˜). AÓ Î·È ÙÔ ˘¿Ú¯ÔÓ ÔÛÙÈÎfi ˘fiÛÙڈ̷ ı· ÌÔÚÔ‡Û ӷ ˘Ô‰Â¯ı› ÔÛÙÂÔÂÓۈ̷ÙÔ‡ÌÂÓ· ÂÌÊ˘Ù‡̷ٷ (EÈÎ. 3), ÂÈϤ¯ıËÎÂ Ë ÔÛÙÈ΋ ·Ó¿Ï·ÛË Ù˘ ÂÚÈÔ¯‹˜, ÁÈ· ÏfiÁÔ˘˜ ÂÌ‚ÈÔÌ˯·ÓÈÎÔ‡˜ ·ÏÏ¿ Î·È Î˘Ú›ˆ˜ ·ÈÛıËÙÈÎÔ‡˜ Î·È ˆ˜ ̤ıÔ‰Ô˜ ·˘Ù‹ Ù˘ ‰È·Ù·ÙÈ΋˜ ÔÛÙÂÔÁ¤ÓÂÛ˘. Yfi ÙÔÈ΋ ·Ó·ÈÛıËÛ›· Î·È Ó¢ÚÔÏËÙ·Ó·ÏÁËÛ›·, ¤ÁÈÓ ÚÔۤϷÛË Ì ÚÔÛÙÔÌÈ·Îfi ÎÚËÌÓfi ÔÏÈÎÔ‡ ¿¯Ô˘˜ ÛÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë Óˆ‰‹ ÂÚÈÔ¯‹ Ù˘ Û‡ÌÊ˘Û˘ Î·È ·ÊÔ‡ ÂÓÙÔ›ÛıËÎ·Ó Î·È ·Ú·Û΢¿ÛÙËÎ·Ó Ù· ÁÂÓÂȷο Ó‡ڷ, ·Ê·ÈÚ¤ıËÎ·Ó ÔÈ Ï¿Î˜ ÔÛÙÂÔÛ‡ÓıÂÛ˘, ·ÎÈÓËÙÔÔÈ‹ıËΠÚÔÛˆÚÈÓ¿ Ë Î·Ù¿ÏÏËÏ· ‰È·ÌÔÚʈı›۷ ÂÓ‰ÔÛÙÔÌ·ÙÈ΋ ‰È·Ù·ÙÈ΋ Û˘Û΢‹ (EÈÎ. 4) Ì ÛÙfi¯Ô ˘ÂÚ‰ÈfiÚıˆÛË Î·È ‰È¿Ù·ÛË 15mm. M ÙËÓ ¯Ú‹ÛË Î·Ù·ÏÏ‹ÏÔ˘ ÏÂÙÔ‡ ‰›ÛÎÔ˘ ¤ÁÈÓÂ Ë ·Ú¯È΋ ÌÂÚÈ΋ ÔÛÙÂÔÙÔÌ›· ÛÙËÓ Óˆ‰‹ ÂÚÈÔ¯‹ (ÂÁÁ‡˜ ÙÔ˘ 35 ¤ˆ˜ ÂÁÁ‡˜ ÙÔ˘ 43) (EÈÎ. 5), ·Ê·ÈÚ¤ıËÎÂ Ë Û˘Û΢‹ Î·È ÔÏÔÎÏËÚÒıËÎÂ Ë ÔÛÙÂÔÙÔÌ›· ‰›ÓÔÓÙ·˜ ȉȷ›ÙÂÚË ÚÔÛÔ¯‹ ÛÙËÓ ·ÎÂÚ·ÈfiÙËÙ· ÙÔ˘ ÁψÛÛÈÎÔ‡ ÎÚËÌÓÔ‡ (EÈÎ. 6). AÎÔÏÔ‡ıˆ˜ ·ӷÙÔÔıÂÙ‹ıËÎÂ Ë Û˘Û΢‹ (EÈÎ. 7) Î·È ·ÊÔ‡ ÂϤÁ¯ıËÎÂ Ë ·ÚfiÛÎÔÙË ÏÂÈÙÔ˘ÚÁ›· Ù˘ (EÈÎ. 8) ¤ÁÈÓ ÂÚÈÔ›ËÛË ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜ Î·È Û‡ÁÎÏÂÈÛ‹ ÙÔ˘ Ì 3:0 Vicryl (EÈÎ. 9). XÔÚËÁ‹ıËΠ·ÓÙÈÌÈÎÚԂȷ΋ Î·È ·Ó·ÏÁËÙÈ΋ ·ÁˆÁ‹ Î·È Ë ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÔÚ›· ÙÔ˘ ·ÛıÂÓÔ‡˜ ‹Ù·Ó ¯ˆÚ›˜ ÂÈÏÔΤ˜ Î·È ¯ˆÚ›˜ ˘·ÈÛıËÛ›· ÛÙËÓ ÂÚÈÔ¯‹ ηٷÓÔÌ‹˜ ÙˆÓ ÁÂÓÂÈ·ÎÒÓ Ó‡ڈÓ. TËÓ ¤ÎÙË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ Ë̤ڷ ¤ÁÈÓÂ Ë ÚÒÙË ÂÓÂÚÁÔÔ›ËÛË Ù˘ Û˘Û΢‹˜, Ë ÔÔ›· ÂÚÈÂÏ¿Ì‚·Ó ̛· Ï‹ÚË ÛÙÚÔÊ‹ ÙÔ˘ ¿ÍÔÓ· Ù˘ Û˘Û΢‹˜ ÙÔ Úˆ› Î·È Ì›· ÙÔ ‚Ú¿‰˘. M ÙÔÓ ÙÚfiÔ ·˘Ùfi ‰ÈÂÙ›ÓÔÓÙ·Ó Ù· ÔÛÙÈο ÎÔÏÔ‚ÒÌ·Ù· ηٿ 1 mm ËÌÂÚËÛ›ˆ˜. MÂÙ¿ ÙËÓ ÚÔÁÚ·ÌÌ·ÙÈṲ̂ÓË ÂÚ›Ô‰Ô ‰È¿Ù·Û˘ ÙˆÓ 15 ËÌÂÚÒÓ Î·È ÙËÓ ·ÎÙÈÓÔÁÚ·ÊÈ΋ ÂȂ‚·›ˆÛË Ù˘ ÚÔ‚ÏÂfiÌÂÓ˘ ˘ÂÚ‰ÈfiÚıˆÛ˘ ÙÔ˘ ÔÛÙÈÎÔ‡ ÂÏÏ›ÌÌ·ÙÔ˜ (EÈÎ. 10), Ë Û˘Û΢‹ ·Ú¤ÌÂÈÓ ·‰Ú·ÓÔÔÈË̤ÓË ÁÈ· ÂÚ›Ô‰Ô 4 ÌËÓÒÓ. AÊÔ‡ ÂȂ‚·ÈÒıËΠ·ÎÙÈÓÔÁÚ·ÊÈο Ë ÂÈÙ˘¯›· Ù˘ ÔÛÙÈ΋˜ ·Ó¿Ï·Û˘, ˘fi ÙÔÈ΋ ·Ó·ÈÛıËÛ›· ¤ÁÈÓ ·Ê·›ÚÂÛË Ù˘ ‰È·Ù·ÙÈ΋˜ Û˘Û΢‹˜ ÂȂ‚·ÈÒıËÎÂ Ë ÔÛÙÈ΋ ·Ó¿Ï·ÛË (EÈÎ. 11) Î·È ÙÔÔıÂÙ‹ıËÎ·Ó 5 ÔÛÙÂÔÂÓۈ̷ÙÔ‡ÌÂÓ· ÂÌÊ˘Ù‡̷ٷ Â͈ÙÂÚÈÎÔ‡ ÂÍ·ÁÒÓÔ˘ ‰È·ÛÙ¿ÛÂˆÓ 3,75 x 15 mm (EÈÎ. 12), Ù· ÔÔ›· ¤¯ÔÓÙ·˜ ÙËÓ Î·Ù¿ÏÏËÏË ÚˆÙÔÁÂÓ‹ ÛÙ·ıÂÚfiÙËÙ· ÊÔÚÙ›ÛıËÎ·Ó ¿ÌÂÛ·. H ÙÂÏÈ΋ ÂÈÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ·ÔηٿÛÙ·ÛË ÙÔÔıÂÙ‹ıËΠÌÂÙ¿ ·Ô 3 Ì‹Ó˜ (EÈÎ.13) Hellenic Stomatological Review 57: 27-37, 2013 EÈÎ. 1: ¶ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÙÔ˘ ·ÛıÂÓÔ‡˜. Fig. 1: Preoperative clinical picture of the patient. EÈÎ. 2: ¶ÚÔÂÁ¯ÂÈÚËÙÈ΋ ·ÓÔÚ·ÌÈ΋ ·ÎÙÈÓÔÁÚ·Ê›·. Fig. 2: Preoperative panoramic x-ray of the patient. two osteosynthesis plates and extensive bone loss which according to preoperative work up was vertically estimated up to 12 mm. Even though the existing bone could easily accept osseointegrated implants (Fig. 3), bone EÈÎ. 3: ¶ÚÔÂÁ¯ÂÈÚËÙÈ΋ ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›·. Fig. 3: Preoperative dental Scan of the patient. 29 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review EÈÎ. 4: ¢È·ÌfiÚʈÛË ‰È·Ù·ÙÈ΋˜ Û˘Û΢‹˜. EÈÎ. 5: ¢ÈÂÓ¤ÚÁÂÈ· Ù˘ ÔÚÈ˙fiÓÙÈ·˜ ÔÛÙÂÔÙÔÌ›·˜. Fig. 4: Extraoral adaptation of the unidirectional distraction device. Fig. 5: The horizontal osteotomy. Î·È Ô ·ÛıÂÓ‹˜ ‚Ú›ÛÎÂÙ·È Û ÂÚÈÔ‰È΋ ·Ú·ÎÔÏÔ‡ıËÛË ÁÈ· Ù¤ÛÛÂÚ· ¯ÚfiÓÈ· ¯ˆÚ›˜ ÛÙÔȯ›· ÊÏÂÁÌÔÓ‹˜. reconstruction before implant placement was decided due to bioengineering as well as aesthetic reasons and the method of DO was chosen. Under local anesthesia with i.v. sedation, through a labial full thickness flap access was achieved to the edentulous region of the symfysis and after the plates were removed, the appropriate type of the internal distraction device was temporarily immobilized aiming to 15mm vertical distraction. Then the first partial osteotomy was done in the edentulous area (proximal of 35 to proximal of 43) (Fig. 5), the device was removed and the osteotomy was completed, while special attention was taken for the integrity of the lingual flap (Fig. 6). Afterwards, the device was reinstalled (Fig. 7) and the mobility of the bone segment was tested, the wound was sutured with 3:0 Vicryl (Fig. 9). Antibiotics and pain control medications were prescribed and the patient’s postoperative course was uncomplicated. The sixth postoperative day the distraction phase began at a rate of 1 mm per day, which was usually applied by activating the device doing a ™YZHTH™H H ¢O ·ÔÙÂÏ› ÌÈ· ÂÓ·ÏÏ·ÎÙÈ΋ ıÂڷ›· ÁÈ· ÙËÓ ·ÔηٿÛÙ·ÛË Ì¤ÙÚÈˆÓ ¤ˆ˜ ÛÔ‚·ÚÒÓ ÔÛÙÈÎÒÓ ÂÏÏÂÈÌÌ¿ÙˆÓ ÛÙËÓ ÚfiÛıÈ· ÂÚÈÔ¯‹ Ù˘ ¿Óˆ ÁÓ¿ıÔ˘ fiÛÔ Î·È ÛÙËÓ ÚfiÛıÈ· Î·È Ô›ÛıÈ· ÂÚÈÔ¯‹ Ù˘ οو ÁÓ¿ıÔ˘2. TÔ ÚˆÙfiÎÔÏÏÔ Ù˘ ¢O fiÙ·Ó ÂÊ·ÚÌfi˙ÂÙ·È ÛÙËÓ ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÚÈÏ·Ì‚¿ÓÂÈ Ù· ·ÎfiÏÔ˘ı· ÛÙ¿‰È·: ñ ¶Ï‹Ú˘ ÔÛÙÂÔÙÔÌ›·. ¢ÈÂÓÂÚÁÔ‡ÓÙ·È Ï‹ÚÂȘ ÔÛÙÂÔÙƠ̂˜, ‰È·ÙËÚÒÓÙ·˜, fiÛÔ Â›Ó·È ‰˘Ó·Ùfi, ÙÔ˘˜ Ì·Ï·ÎÔ‡˜ ÈÛÙÔ‡˜ ÚÔÛÎÔÏÏË̤ÓÔ˘˜ ÁÈ· Ó· ÂÍ·ÛÊ·ÏÈÛı› Ë Â·Ú΋˜ ·ÈÌ¿ÙˆÛË ÙÔ˘ ÔÛÙÈÎÔ‡ ÎÔÏÔ‚ÒÌ·ÙÔ˜. ñ §·Óı¿ÓÔ˘Û· ÂÚ›Ô‰Ô˜. E›Ó·È Ë ÂÚ›Ô‰Ô˜ ÙˆÓ 7 ÌÂÙÂÁ¯ÂÈÚËÙÈÎÒÓ ËÌÂÚÒÓ Î·Ù¿ ÙËÓ ÔÔ›· ‰ÂÓ Á›ÓÂÙ·È ÂÓÂÚÁÔÔ›ËÛË Ù˘ Û˘Û΢‹˜, Ô‡Ùˆ˜ ÒÛÙ ›Ó˜ ÎÔÏÏ·ÁfiÓÔ˘ Ù‡Ô˘ I Ó· Û¯ËÌ·ÙÈÛÙÔ‡Ó ÛÙÔÓ ÒÚÔ ‰È¿Ù·Û˘. A˘Ù¤˜ ÔÈ ›Ó˜ ·Ó·Ù‡ÛÛÔÓÙ·È ÂÚ›Ô˘ 5 ¤ˆ˜ 6 Ë̤Ú˜ ÌÂÙ¿ ÙËÓ ÔÛÙÂÔÙÔÌ›·. ñ ¶ÂÚ›Ô‰Ô˜ ÂÓÂÚÁÔÔ›ËÛ˘. A˘Ù‹ Ë ÂÚ›Ô‰Ô˜ ÍÂÎÈÓ¿ ÙËÓ ¤‚‰ÔÌË Ë̤ڷ Î·È ‰È·ÚΛ ̤¯ÚÈ Ë ‰È·Ù·ÙÈ΋ Ͽη Ó· οÓÂÈ ÙËÓ ÚÔÁÚ·ÌÌ·ÙÈṲ̂ÓË ÌÂٷΛÓËÛË, Ë ÔÔ›· ¤¯ÂÈ Û¯Â‰È·ÛÙ› ÂÎ ÙˆÓ ÚÔÙ¤ÚˆÓ ÛÙÔ ‰È·ÁÓˆÛÙÈÎfi Τڈ̷, Ì 20-30% ˘ÂÚ‰ÈfiÚıˆÛË. ñ ¶ÂÚ›Ô‰Ô˜ ÛÙ·ıÂÚÔÔ›ËÛ˘. O ¯ÚfiÓÔ˜ ÁÈ· ÙËÓ Ï‹ÚË ÂÓ·Û‚ÂÛÙ›ˆÛË ÙÔ˘ Ó¤Ô˘ ÔÛÙÔ‡ ÌÔÚ› Ó· ‰È·ÚΤÛÂÈ ·fi 10 ¤ˆ˜ 12 Ì‹Ó˜. IÛÙÔÏÔÁÈο, ÛÙȘ 8 ‚‰ÔÌ¿‰Â˜, ·Ú·ÙËÚÂ›Ù·È ¤ÓÙÔÓË ÂÓÂÚÁ‹˜ ÔÛÙÈ΋ ·Ó·‰È·ÌfiÚʈÛË Û fiÏË ÙËÓ ¤ÎÙ·ÛË ÙÔ˘ ‰È·Ù·ÙÈÎÔ‡ ÒÚÔ˘. OÈ ‰‡Ô ¿ÎÚ˜ ÙÔ˘ ‰È·ÙÂٷ̤ÓÔ˘ ÔÛÙÔ‡ ¤Ú¯ÔÓÙ·È Û ·ʋ Ì ÙÔ ÓÂÔÛ¯ËÌ·ÙÈÛı¤Ó ‰ÔÎȉ҉˜ ÔÛÙfi Î·È ÂÚÈ‚¿ÏÏÔÓÙ·È ·fi ÔÏÏ·Ï·ÛÈ·˙fiÌÂÓ˜ ÔÛÙÂÔ‚Ï¿ÛÙ˜. EÈÚfiÛıÂÙ·, Ô ÚÔÛ·Ó·ÙÔÏÈÛÌfi˜ ÙÔ˘ Ó¤Ô˘ ÔÛÙÔ‡ Â›Ó·È ·Ú¿ÏÏËÏÔ˜ Ì ÙË ‰È‡ı˘ÓÛË Ù˘ ‰È¿Ù·Û˘. ñ TÔÔı¤ÙËÛË ÂÌÊ˘Ù‡̷ÙÔ˜. H ÙÔÔı¤ÙËÛË ÙˆÓ ÂÌ30 EÈÎ. 6: OÏÔÎÏ‹ÚˆÛË ÙˆÓ ÔÛÙÂÔÙÔÌÈÒÓ Ì ÔÛÙÂÔÙfiÌÔ. Fig. 6: Completing the osteotomies with osteotomes. Hellenic Stomatological Review 57: 27-37, 2013 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review complete turn of the axis of the device once in the morning and once in the evening. After the predetermined period of 15 days distraction and radiographic confirmation of predicted overcorrection of the bone defect (Fig. 10), the device remained in place for a EÈÎ. 7: TÂÏÈ΋ ÙÔÔı¤ÙËÛË Ù˘ Û˘Û΢‹˜. Fig. 7: The final placement of the device. EÈÎ. 10: AÎÙÈÓÔÁÚ·ÊÈ΋ ÂÈÎfiÓ· ÙÔ˘ ·ÛıÂÓÔ‡˜ ÌÂÙ¿ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË Ù˘ Û˘Û΢‹˜. Fig. 10: Radiographical picture of the patient after device activation. period of four months (consolidation period). After radiographic confirmation of successful bone regeneration under local anesthesia the distraction device was removed, bone regeneration was confirmed (Fig. 11) and 5 EÈÎ. 8: ŒÏÂÁ¯Ô˜ Ù˘ ·ÚfiÛÎÔÙ˘ ΛÓËÛ˘ ÙÔ˘ ÎÈÓËÙÔ‡ ÎÔÏÔ‚ÒÌ·ÙÔ˜ Fig. 8: Testing the movement of the movable bone segment. EÈÎ. 11: OÛÙÈÎfi ˘fiÛÙڈ̷ ÌÂÙ¿ ÙÔ ¤Ú·˜ Ù˘ ‰È·Ù·ÙÈ΋˜ ÔÛÙÂÔÁ¤ÓÂÛ˘. Fig. 11: New bone formation between the two bone segments. EÈÎ. 9: ™˘ÚÚ·Ê‹ ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜. osseointegrated implants dimensions 3,75 x 15 mm were placed (Fig. 12) and immediately loaded, since they had the appropriate primary stability. The final implant restoration was delivered after 3 months (Fig. 13) and the patient has periodic follow up for the last four years without any sign of inflammation. Fig. 9: The closure of the wound. Hellenic Stomatological Review 57: 27-37, 2013 31 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review Ê˘ÙÂ˘Ì¿ÙˆÓ Á›ÓÂÙ·È 3 - 4 Ì‹Ó˜ ÌÂÙ¿ ÙÔ ÚÒÙÔ ¯ÂÈÚÔ˘ÚÁÈÎfi ÛÙ¿‰ÈÔ. EÂȉ‹ Ë ÙÂÏÈ΋ ‰È·ÌfiÚʈÛË Î·È ˆÚ›Ì·ÓÛË (ÌÂÙ·ÏÏÔÔ›ËÛË) ÙÔ˘ ÓÂÔÛ¯ËÌ·ÙÈÛı¤ÓÙÔ˜ ÔÛÙÔ‡ ÌÔÚ› Ó· ‰È·ÚΤÛÂÈ ¤ˆ˜ Î·È 12 Ì‹Ó˜, ÁÈ· ·˘Ùfi ÙÔ ÏfiÁÔ Ù· ÂÌÊ˘Ù‡̷ٷ Ú¤ÂÈ Ó· ¤¯Ô˘Ó ·ÚÎÂÙfi Ì‹ÎÔ˜ ÁÈ· Ó· ÊÙ¿ÛÔ˘Ó Î·È Ó· ‰È·ÂÚ¿ÛÔ˘Ó ÙÔ ÓÂÔÛ¯ËÌ·ÙÈṲ̂ÓÔ ÔÛÙfi ηıfiÏÔ ÙÔ ‡„Ô˜ ÙÔ˘ , ÒÛÙ ӷ ÂÈÙ¢¯ı› ÛÙ·ıÂÚfiÙËÙ· ÙÔ˘ ÔÛÙÔ‡ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÙÂÏÈ΋˜ ÂÚÈfi‰Ô˘. ŸÛÔÓ ·ÊÔÚ¿ ÙËÓ ¯ÂÈÚÔ˘ÚÁÈ΋ Ù¯ÓÈ΋ Ù˘ ¢O Ë fiÛÔ ÙÔ ‰˘Ó·ÙfiÓ ÏÈÁfiÙÂÚË ·ÔÎfiÏÏËÛË ÙÔ˘ ÂÚÈÔÛÙ¤Ô˘ ·fi ÙÔ ÔÛÙÈÎfi ˘fiÛÙڈ̷ Î·È Ë ·ÚfiÛÎÔÙË ·ÈÌ¿ÙˆÛ‹ ÙÔ˘ ıˆÚÂ›Ù·È ÚˆÙ·Ú¯È΋˜ ÛËÌ·Û›·˜ ÁÈ· ÙË ‚ÂÏÙÈÛÙÔÔ›ËÛË ÙÔ˘ ÔÛÙÂÔÁÂÓÂÙÈÎÔ‡ ‰˘Ó·ÌÈÎÔ‡ ÙÔ˘ ÔÛÙÔ‡-ÍÂÓÈÛÙ‹. AÓ ÙÔ ÙÌ‹Ì· Ô˘ ÚfiÎÂÈÙ·È Ó· ÔÛÙÂÔÙÔÌËı› Â›Ó·È ·ÔÎÔÏÏË̤ÓÔ ·fi Ù· ÁÂÈÙÔÓÈο ̷Ϸο ÌfiÚÈ·, ÙfiÙ ·˘Ùfi ı· Û˘ÌÂÚÈÊÂÚı› ˆ˜ ÂχıÂÚÔ ÔÛÙÈÎfi ÌfiÛ¯Â˘Ì·, Ì ÛÔ‚·ÚÔ‡ Î·È ·Úfi‚ÏÂÙÔ˘ ‚·ıÌÔ‡ ·ÔÚÚfiÊËÛË. H ÔÛÙÂÔÙÔÌ›· Ú¤ÂÈ Ó· ‰ÈÂÓÂÚÁÂ›Ù·È ˘fi ηٷÈÔÓÈÛÌfi Ê˘ÛÈÔÏÔÁÈÎÔ‡ ÔÚÔ‡ ÒÛÙ ӷ ‰È·ÙËÚËı› Ë ıÂÚÌÔÎÚ·Û›· ÂÓÙfi˜ ‚ÈÔÏÔÁÈÎÒÓ ÔÚ›ˆÓ, ·ÔʇÁÔÓÙ·˜ ÙËÓ ˘ÂÚı¤ÚÌ·ÓÛË ÙÔ˘ ÔÛÙÔ‡. H οıÂÙË ÔÛÙÂÔÙÔÌ›· ‰ÂÓ Ú¤ÂÈ Ó· Ú·ÁÌ·ÙÔÔÈÂ›Ù·È Ôχ ÎÔÓÙ¿ ÛÙ· ·Ú·Î›ÌÂÓ· ‰fiÓÙÈ· ÏfiÁˆ ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ·ÔÎ¿Ï˘„˘ Ù˘ ÂÈÊ¿ÓÂÈ·˜ Ù˘ Ú›˙·˜ ÌÂ Û˘Ó¤ÂÈ· ÙËÓ Î·ı˘ÛÙ¤ÚËÛË ÛÙÔ Û¯ËÌ·ÙÈÛÌfi Ó¤Ô˘ ÔÛÙÔ‡ Î·È ÙËÓ Î·Ù·ÛÙÚÔÊ‹ ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Ù˘ ÂÚÈÔ¯‹˜. H ÔÚÈ˙fiÓÙÈ· ÔÛÙÂÔÙÔÌ›· Ú¤ÂÈ Ó· Ú·ÁÌ·ÙÔÔÈÂ›Ù·È ¤ÙÛÈ ÒÛÙ ӷ ‰ËÌÈÔ˘ÚÁÂ›Ù·È fiÛÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÙÈÎfi ÎÔÏfi‚ˆÌ· Á›ÓÂÙ·È ¯ˆÚ›˜ Ó· Ù›ıÂÙ·È Û ΛӉ˘ÓÔ Ë ·ÎÂÚ·ÈfiÙËÙ· ÙÔ˘ ÔÛÙÔ‡ Ô˘ ·Ú·Ì¤ÓÂÈ. TÔ ÂÏ¿¯ÈÛÙÔ ‡„Ô˜ ÔÛÙÔ‡ ÁÈ· ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ Ù¯ÓÈ΋˜ Ù˘ ¢O Â›Ó·È ÁÈ· ÙËÓ ¿Óˆ ÁÓ¿ıÔ 8 mm Î·È ÁÈ· ÙË Î¿Ùˆ 15 mm ¤ÙÛÈ ÒÛÙ ӷ ·ÔÊ¢¯ıÔ‡Ó ·ÓÂÈı‡ÌËÙ· ηٿÁÌ·Ù·. O Û¯ËÌ·ÙÈÛÌfi˜ Ó¤Ô˘ ÔÛÙÔ‡ ÚԂϤÂÙ·È Î·Ï‡ÙÂÚ· ·Ó ÛÙËÓ ÔÚÈ˙fiÓÙÈ· ÔÛÙÂÔÙÔÌ›· Â›Ó·È ·Ó·ÏÔÁÈο ÂÚÈÛÛfiÙÂÚË Ë Ì˘ÂÏ҉˘ ÌÔ›Ú· ÙÔ˘ ÔÛÙÔ‡ Û ۯ¤ÛË Ì ÙË ÊÏÔÈÒ‰Ë4. M ÙËÓ ÔÏÔÎÏ‹ÚˆÛË Ù˘ ÔÛÙÂÔÙÔÌ›·˜, Ú¤ÂÈ Ó· Á›ÓÂÈ ÚÔÛÂÎÙÈ΋ Û‡ÁÎÏÂÈÛË ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜, ¤ÙÛÈ ÒÛÙ ӷ ·ÔʇÁÂÙ·È Ë ‰È¿Û·Û‹ ÙÔ˘ Î·È Ë ÂÈÌfiÏ˘ÓÛË, ·fi ÙÚÔʤ˜ ‹ Û›·ÏÔ, Ù˘ ÔÛÙÈ΋˜ ÎÔÈÏfiÙËÙ·˜ Î·È Ó· ‰È¢ÎÔχÓÂÙ·È Ë ÂÓ·fiıÂÛË ·Ï¿ÙˆÓ Û fiÏÔ ÙÔ Â‡ÚÔ˜ ÙÔ˘ ÔÛÙÔ‡. ŸÛÔÓ ·ÊÔÚ¿ ÙȘ ÂÈÏÔΤ˜ Ù˘ ¢O, Û’ ·˘Ù¤˜ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ë Ï·Óı·Ṳ̂ÓË Î·Ù‡ı˘ÓÛË ÌÂٷΛÓËÛ˘ ÙÔ˘ ‰È·ÙÂٷ̤ÓÔ˘ ÙÌ‹Ì·ÙÔ˜, Ë ·ÔÎ¿Ï˘„Ë Ù˘ ‰È·Ù·ÙÈ΋˜ Û˘Û΢‹˜, Ë ıÚ·‡ÛË Ù˘ Û˘Û΢‹˜, Ë ·‰˘Ó·Ì›· ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ ‰È·Ù·ÙÈ΋˜ Û˘Û΢‹˜ Î·È Û·ÓÈfiÙÂÚ· Ô ÙÚ·˘Ì·ÙÈÛÌfi˜ ÙÔ˘ ÙÚ›ÙÔ˘ ÎÏ¿‰Ô˘ ÙÔ˘ ÙÚȉ‡ÌÔ˘ Î·È ÙÔ Î¿Ù·ÁÌ· Ù˘ οو ÁÓ¿ıÔ˘4. H ¢O ·ÔÙÂÏ› ÌÈ· ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË Ì Ôχ ηϿ ÌÂÙÂÁ¯ÂÈÚËÙÈο ·ÔÙÂϤÛÌ·Ù·. K·Ù’ ·Ú¯‹Ó ¤Ó· ·fi Ù· ·ÚÈ· ÏÂÔÓÂÎÙ‹Ì·Ù¿ Ù˘ Û ۯ¤ÛË Ì ÙȘ ¿ÏϘ Ù¯ÓÈΤ˜ Â›Ó·È Ë ‰È¿Ù·ÛË ÙˆÓ Ì·Ï·ÎÒÓ ÈÛÙÒÓ Ù˘ ÂÚÈÔ¯‹˜ Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ÙÔ˘ Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡, ÙˆÓ Ì˘ÒÓ, ÙÔ˘ ÂÈıËÏ›Ô˘, ÙÔ˘ ÂÚÈÔÛÙ¤Ô˘, ÙˆÓ ·ÁÁ›ˆÓ Î·È ÙˆÓ Ó‡ڈÓ, Ô˘ ¤¯ÂÈ ˆ˜ ·ÎfiÏÔ˘ıÔ ÙËÓ ÌÂȈ̤ÓË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ·ÔÚÚfiÊËÛË ÙÔ˘ ‰È·ÙÂٷ̤ÓÔ˘ ÔÛÙÈÎÔ‡ ÙÌ‹Ì·ÙÔ˜. E›Û˘, Ë ÙÔÔı¤ÙËÛË ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ Â›Ó·È ‰˘Ó·Ù‹ Û ÂÍ·ÈÚÂÙÈο Û‡ÓÙÔÌË ÂÚ›Ô‰Ô (8-12 ‚‰ÔÌ¿32 EÈÎ. 12: TÔÔı¤ÙËÛË ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ. Fig. 12: The placement of the implants. EÈÎ. 13: TÂÏÈ΋ ÚÔÛıÂÙÈ΋ ·ÔηٿÛÙ·ÛË. Fig. 13: The final prosthesis. DISCUSSION DO is considered to be an alternative treatment for the reconstruction of moderate to severe bone defects in the anterior maxilla as well as in the anterior and posterior mandible2. The distraction protocol in the pre-implant surgery includes the following phases: ñ Surgical phase: Complete segmental osteotomies are carried out, maintaining the soft tissues attached, as much as possible, to ensure adequate vascularization. ñ Latency phase: This includes the 7 postoperative days, in which the device is left without any activation to allow the collagen type I fibers to form at the distraction site. These fibers are being developed 5 to 6 days approximately after the osteotomy. ñ Distraction or Activation phase: This period starts on the seventh day and lasts until the appropriate amount of distraction bone has been achieved. The amount of distraction is determined in advance on the prediction wax-up, with 20-30% of overcorrection. Hellenic Stomatological Review 57: 27-37, 2013 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review ‰Â˜) ÌÂÈÒÓÔÓÙ·˜ ·ÚÎÂÙ¿ ÙÔ ¯ÚfiÓÔ ıÂڷ›·˜ ÙÔ˘ ·ÛıÂÓÔ‡˜. O ıÂÚ¿ˆÓ È·ÙÚfi˜ ¤¯ÂÈ ÙËÓ ÈηÓfiÙËÙ· ÎÏÈÓÈÎÔ‡ ÂϤÁ¯Ô˘ Î·È ·Ú¤Ì‚·Û˘ ηı’ fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ·‡ÍËÛ˘ ÙÔ˘ ÔÛÙÈÎÔ‡ ˘ÔÛÙÚÒÌ·ÙÔ˜. EÈÚÔÛı¤Ùˆ˜ Ë ‰ËÌÈÔ˘ÚÁ›· Ê˘ÛÈÎÔ‡ ·˘ÙÔÁÂÓÔ‡˜ ÔÛÙÔ‡ ÛÙË ÂÚÈÔ¯‹ ÙÔ˘ ÂÏÏ›ÌÌ·ÙÔ˜ ˘ÂÚ¤¯ÂÈ Î·Ù¿ Ôχ Û ۇÁÎÚÈÛË Ì ÙËÓ ¯ÚËÛÈÌÔÔ›ËÛË ÔÛÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜, ·ÎfiÌË Î·È ·˘ÙÔÁÂÓÔ‡˜, Ô˘ ı· ›¯Â Û·Ó ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ó¿ÁÎË ‰Â˘Ù¤ÚÔ˘ ¯ÂÈÚÔ˘ÚÁÈÎÔ‡ ÙÚ·‡Ì·ÙÔ˜ ·fi ÙË ‰fiÙÚÈ· ı¤ÛË ·ÏÏ¿ Î·È ÙË Èı·Ó‹ ÂÌÊ¿ÓÈÛË ÂÈÏÔÎÒÓ ÛÙË ÂÚÈÔ¯‹ ·˘Ù‹. T¤ÏÔ˜ Ë ·ÔÊ˘Á‹ ¯ÚËÛÈÌÔÔ›ËÛ˘ Í¤ÓˆÓ ˘ÏÈÎÒÓ ÚÔ˜ ÙÔÓ ÔÚÁ·ÓÈÛÌfi ·ÔÙÂÏ› ¤Ó·Ó ·ÎfiÌË ‚·ÛÈÎfi ÏfiÁÔ ˘ÂÚÔ¯‹˜ Ù˘ ‰È·Ù·ÙÈ΋˜ ÔÛÙÂÔÁ¤ÓÂÛ˘ Û ۯ¤ÛË Ì ÙȘ ¿ÏϘ Ù¯ÓÈΤ˜ ÔÛÙÈ΋˜ ·Ó¿Ï·Û˘ fiÔ˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÍÂÓÔÌÔۯ‡̷ٷ ‹ ·ÏÏÔÌÔۯ‡̷ٷ5-10. ™Ù· ÌÂÈÔÓÂÎÙ‹Ì·Ù· Ù˘ Ù¯ÓÈ΋˜ ÂÚÈÏ·Ì‚¿ÓÂÙ·È Ô ·˘ÍË̤ÓÔ˜ ΛӉ˘ÓÔ˜ ÙÚ·˘Ì·ÙÈÛÌÔ‡ ÙÔ˘ οو Ê·ÙÓÈ·ÎÔ‡ Ó‡ÚÔ˘, Û ÂÚÈÙÒÛÂȘ ·‡ÍËÛ˘ ÙÔ˘ ‡„Ô˘˜ ÙÔ˘ ÔÛÙÈÎÔ‡ ˘ÔÛÙÚÒÌ·ÙÔ˜ ÛÙËÓ Ô›ÛıÈ· ÂÚÈÔ¯‹ Ù˘ οو ÁÓ¿ıÔ˘. E›Û˘ Ë ¯Ú‹ÛË ‰È·‚ÏÂÓÓÔÁÔÓ›Ô˘ Ù‡Ô˘ Û˘Û΢‹˜ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ‰È¿Û·ÛË ÙˆÓ ÎÚËÌÓÒÓ Î·È Èı·Ó‹ ÂÈÌfiÏ˘ÓÛË Ù˘ ÂÚÈÔ¯‹˜. H ‡·ÚÍË Ù˘ Û˘Û΢‹˜ ÛÙË Ì¤Ó ÚfiÛıÈ· ÂÚÈÔ¯‹ ÌÔÚ› Ó· ‰ËÌÈÔ˘ÚÁ‹ÛÂÈ ·ÈÛıËÙÈÎfi Úfi‚ÏËÌ· ÛÙÔÓ ·ÛıÂÓ‹, ÂÓÒ Û ÔÔÈ·‰‹ÔÙ ı¤ÛË Èı·ÓfiÓ Ó· ‰ËÌÈÔ˘ÚÁ‹ÛÂÈ ÚÔ‚Ï‹Ì·Ù· ηٿ ÙËÓ ÔÌÈÏ›·, ÙË Ì¿ÛËÛË ·ÏÏ¿ Î·È ‰˘Û¯¤ÚÂÈ· ÛÙË ÛÙÔÌ·ÙÈ΋ ˘ÁÈÂÈÓ‹. OÈ ÂÚÈÛÛfiÙÂÚ˜ ‰È·Ù·ÙÈΤ˜ Û˘Û΢¤˜ ÌÔÚÔ‡Ó Ó· ÂÈÙ‡¯Ô˘Ó ·‡ÍËÛË ÙˆÓ ‰È·ÛÙ¿ÛÂˆÓ Ù˘ ÁÓ¿ıÔ˘ Û ¤Ó· ÌfiÓÔ Â›Â‰Ô. K·Ù¿ Û˘Ó¤ÂÈ· fiÙ·Ó ÂÈı˘ÌÂ›Ù·È ÂÎÙfi˜ ·fi ‰ÈfiÚıˆÛË ÙÔ˘ ‡„Ô˘˜ Î·È ÙÔ Â‡ÚÔ˜ Ù˘ ÁÓ¿ıÔ˘, ηÏfi Â›Ó·È ÙÔ Û¯¤‰ÈÔ ıÂڷ›·˜ Ó· ÛÙÚ¤ÊÂÙ·È Û ¿ÏϘ Ù¯ÓÈΤ˜. T¤ÏÔ˜ Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ Ë ¢O Â›Ó·È ÌÈ· ıÂڷ›· Ì ۯÂÙÈο ·˘ÍË̤ÓÔ ÎfiÛÙÔ˜ Î·È ··ÈÙÂ›Ù·È È‰È·›ÙÂÚË ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÌÂÈÚ›·, ÂÓÒ Ë ÈηÓÔÔÈËÙÈ΋ ¤Î‚·ÛË Ù˘ ÂÍ·ÚÙ¿Ù·È Û ÌÂÁ¿ÏÔ ‚·ıÌfi ·fi ÙËÓ ·fiÏ˘ÙË Û˘ÓÂÚÁ·Û›· ÙÔ˘ ·ÛıÂÓÔ‡˜7-9. ™Ù· Ï·›ÛÈ· Ù˘ ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋˜ ¯ÂÈÚÔ˘ÚÁÈ΋˜ ¤¯Ô˘Ó ‰ËÌÔÛÈ¢ı› ‰È¿ÊÔÚ˜ ÌÂϤÙ˜, ÛÙȘ Ôԛ˜ Û˘ÁÎÚ›ÓÔÓÙ·È Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ¢O Û ۯ¤ÛË Ì ٷ ÔÛÙÈο ÌÔۯ‡̷ٷ. TÔ 2004, Ô Chiapasco Î·È Û˘ÓÂÚÁ¿Ù˜ Û ÌÈ· ¤Ú¢ӷ Û‡ÁÎÚÈÓ·Ó Ù· ÎÏÈÓÈο ·ÔÙÂϤÛÌ·Ù· Ù˘ Ù¯ÓÈ΋˜ Ù˘ ¢O Û ۯ¤ÛË Ì ٷ ÔÛÙÈο ÌÔۯ‡̷ٷ Û ÂÏÏÂÈÌÌ·ÙÈΤ˜ ·ÎÚÔÏÔʛ˜ Ì οıÂÙÔ ¤ÏÏÂÈÌÌ· ÔÛÙÔ‡. H ¤Ú¢ӷ ·˘Ù‹ ·ÍÈÔÏfiÁËÛ ·Ú·Ì¤ÙÚÔ˘˜ fiˆ˜ ÙËÓ ÔÛÙÈ΋ ·ÔÚÚfiÊËÛË ÚÈÓ Î·È ÌÂÙ¿ ÙË ÙÔÔı¤ÙËÛË ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ Î·È ÙËÓ ÂÚÈÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ÔÛÙÈ΋ ·ÒÏÂÈ· ÛÙÔ ÚÒÙÔ, ÙÔ ‰Â‡ÙÂÚÔ Î·È ÙÔ ÙÚ›ÙÔ ¯ÚfiÓÔ ÌÂÙ¿ ÙËÓ ÙÔÔı¤ÙËÛË Ù˘ ÚÔÛıÂÙÈ΋˜ ·ÔηٿÛÙ·Û˘. T· ·ÔÙÂϤÛÌ·Ù· ¤‰ÂÈÍ·Ó fiÙÈ Ë ‰È·Ù·ÙÈ΋ ÔÛÙÂÔÁ¤ÓÂÛË Ê·›ÓÂÙ·È Ó· ˘ÂÚ¤¯ÂÈ fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ·ÎÂÚ·ÈfiÙËÙ· ÙÔ˘ ÂÚÈÂÌÊ˘ÙÂ˘Ì·ÙÈÎÔ‡ ÔÛÙÔ‡11. ÕÏÏË Ì›· ¤Ú¢ӷ ÙˆÓ Chiapasco M. Î·È Û˘Ó. ÙÔ 2007, Ô˘ Û˘Ó¤ÎÚÈÓ ÙËÓ Ù¯ÓÈ΋ ÙˆÓ ·˘ÙfiÏÔÁˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È Ù˘ ¢O Û ۇÓÔÏÔ 17 ·ÛıÂÓÒÓ, ¤‰ÂÈÍ fiÙÈ Ë ÔÛÙÈ΋ ·ÔÚÚfiÊËÛË ÚÈÓ ÙËÓ ÙÔÔı¤ÙËÛË ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ ‹Ù·Ó ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ÛÙËÓ ÔÌ¿‰· Ô˘ ‰¤¯ıËΠٷ ÌÔۯ‡̷ٷ. AÓÙÈı¤Ùˆ˜, ‰Â ‚Ú¤ıËÎ·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ fiÛÔÓ ·ÊÔÚ¿ Ù· Hellenic Stomatological Review 57: 27-37, 2013 ñ Consolidation phase: The time for complete mineralization may extend from 10 to 12 months. However, histologically, at 8 weeks, very active remodelling occurs throughout the distraction chamber. Both sides of the distracted bone edges contact newly formed bone trabeculae and are surrounded by proliferating osteoblasts. Additionally, the orientation of the new bone is parallel to the direction of the distraction. ñ Implant placement: The insertion of dental implants takes place 3 or 4 months after the first surgical stage. Since the final formation and mineralization of the new bone may extend up to 12 months, the implants need to be long enough to reach and penetrate the newly made bone through its whole height, in order to achieve bone stability during the final period. As far as the surgical technique is concerned, preservation of the periosteum attachment to the bone and the endosteal blood supply are considered to be of primary importance to optimizing the osteogenic potential of the host bone. If the segment which is going to be osteotomized is detached from the adjacent soft tissues, then it will act as a free bone graft, with a severe and unpredictable degree of resorption. The osteotomy must be carried out under abundant irrigation to conserve the temperature within biologic limits, avoiding bone overheating. The vertical osteotomy should not be performed right next to the adjacent teeth, because of the risk of exposing the root surface, which may cause slower bone formation and damage to periodontal tissues within this area. The horizontal osteotomy should be positioned to construct a transport segment as large as possible without compromising the integrity of the remaining bone. The minimal bone height of the maxilla is 8mm and 15mm for the mandible, to avoid undesired fractures. Osseous formation can be better predicted if at the horizontal osteotomy the medullary space is proportionally more than the cortical bone4. Once the osteotomies are completed, the wound must be carefully sutured, in order to avoid saliva and food contamination into the distraction champer and to facilitate full bone mineralization. Concerning the complications of the procedure incorrect distraction vector, distraction device exposure, distraction device fracture, inability to activate the device and rarely injuries concerning the third branch of trigeminal nerve and fracture of the mandible are included4. DO is a surgical procedure with predictable postoperative results. One of the main advantages of DO compared to other techniques is the simultaneous distraction of local soft tissues, in which are included the connective tissue, the muscles, the epithelium, the periosteum, the vessels and the nerves, which has as a result of minimum bone absorption after the surgery. Moreover, in addition to mucosal distraction a soft tissue augmentation is counted along with connective tissue, muscle, epithelium, periosteal, vessels and nerves. Furthermore, implant placement is able during a short time frame (4- 8 weeks), decreasing sufficiently patients treatment time. The 33 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review ÔÛÔÛÙ¿ ÂÈ‚›ˆÛ˘ Î·È ÂÈÙ˘¯›·˜ ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ, fiˆ˜ ›Û˘ Î·È ÙËÓ ÂÚÈÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ÔÛÙÈ΋ ·ÔÚÚfiÊËÛË ‡ÛÙÂÚ· ·fi ÙË ÊfiÚÙÈÛË ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ12. OÈ Perez-Sayans Î·È Û˘Ó. (2008) ‰ÂÓ ¤‰ÂÈÍ·Ó ‰È·ÊÔÚ¿ ÛÙË Î¿ıÂÙË ·ÔÚÚfiÊËÛË Û ‰È·ÙÂٷ̤ÓÔ Î·È ÌË ‰È·ÙÂٷ̤ÓÔ ÔÛÙfi, ÂÓÒ Ë ÂÈÙ˘¯›· ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ Â›¯Â Ù· ›‰È· ÂÚ›Ô˘ ÔÛÔÛÙ¿ Î·È ÛÙȘ ‰‡Ô Ù¯ÓÈΤ˜13. O Uckan Î·È Û˘Ó. (2007) ÌÂϤÙËÛ·Ó ÙËÓ ÂÈ‚›ˆÛË ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ Î·È ÙȘ ÂÈÏÔΤ˜ ηٿ ÙËÓ ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ Û ÔÌ¿‰Â˜ ·ÛıÂÓÒÓ ÛÙȘ Ôԛ˜ ›¯Â ÚÔËÁËı› ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋ ›Ù Ì ¢O ›Ù Ì ·˘ÙfiÏÔÁ· ÔÛÙÈο ÌÔۯ‡̷ٷ. T· ·ÔÙÂϤÛÌ·Ù· ÙÔ˘˜ ¤‰ÂÈÍ·Ó ¤Ó· ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ÂÈÏÔÎÒÓ ÛÙË ¢O (66,8% ¤Ó·ÓÙÈ 33,8%). OÈ ÂÈÏÔΤ˜ ·˘Ù¤˜ fï˜ ‰ÂÓ ‹Ù·Ó ÙfiÛÔ ÛÔ‚·Ú¤˜ Û ۯ¤ÛË Ì ·˘Ù¤˜ Ô˘ ÂÌÊ·Ó›ÛÙËÎ·Ó Î·Ù¿ ÙË ıÂڷ›· Ì ·˘ÙÔÌfiÛ¯Â˘Ì·. K·È Û ·˘Ù‹ ÙË ÌÂϤÙË Ë ÂÈÙ˘¯›· ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ ‹Ù·Ó ·ÚfiÌÔÈ· (91,4% ¢O ¤Ó·ÓÙÈ 93,7 ÌfiÛ¯Â˘Ì·)14. TÔ 2005, Ô Enislidis G. Î·È Û˘Ó. Ú·ÁÌ·ÙÔÔ›ËÛ·Ó ÌÈ· ·Ó·‰ÚÔÌÈ΋ ¤Ú¢ӷ ÁÈ· Ó· ·ÍÈÔÏÔÁ‹ÛÔ˘Ó ÙȘ ÂÈÏÔΤ˜ ÚÈÓ, ηٿ ÙË ‰È¿ÚÎÂÈ· Î·È ÌÂÙ¿ ÙË ‰ÈÂÓ¤ÚÁÂÈ· ¢O Û ÔÚÈ˙fiÓÙÈÔ Â›Â‰Ô, ηıÒ˜ Î·È ÁÈ· Ó· ÂÎÙÈÌ‹ÛÔ˘Ó Ù· ÔÛÔÛÙ¿ ÂÈ‚›ˆÛ˘ ÙˆÓ Ô‰ÔÓÙÈÎÒÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ Ô˘ ÙÔÔıÂÙ‹ıËÎ·Ó ÛÙȘ ‰È·ÙÂٷ̤Ó˜ ÂÚÈÔ¯¤˜. ™Â ÔÛÔÛÙfi 75,7% ·ÚÔ˘ÛÈ¿ÛıËÎ·Ó ÂÈÏÔΤ˜ Û¯ÂÙÈ˙fiÌÂÓ˜ Ì ÙË ‰È¿Ù·ÛË, fï˜ ÛÙËÓ ÏÂÈÔ„ËÊ›· ÙÔ˘˜ ‹Ù·Ó ‹ÛÛÔÓÔ˜ ÛËÌ·Û›·˜, ÂÓÒ ÙÔ ÔÛÔÛÙfi ÂÈ‚›ˆÛ˘ ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ ‹Ù·Ó 95,7%15. AÓÙÈı¤Ùˆ˜ ÔÈ Bianchi Î·È Û˘Ó. (2008) ¤‰ÂÈÍ·Ó fiÙÈ ·Ó Î·È Ë ·Ó¿Ï·ÛË ÔÛÙÔ‡ Ì Ù¯ÓÈΤ˜ ¢O ‹Ù·Ó ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË (10 mm ¤Ó·ÓÙÈ 5,8 mm), ÙÔ ÔÛÔÛÙfi ÂÈÏÔÎÒÓ ‹Ù·Ó ηٿ Ôχ ÌÂÁ·Ï‡ÙÂÚÔ ÛÙË ¢O (60%) Û ۯ¤ÛË Ì ÙË ¯Ú‹ÛË ·˘ÙÔÌÔۯ‡̷ÙÔ˜ (14,3%)16. TÔ 2008, ÔÈ Froum Î·È Û˘Ó. ‰ËÌÔÛ›Â˘Û·Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÌÈ·˜ ¤Ú¢ӷ˜ Ô˘ ·ÊÔÚÔ‡Û 30 ·ÛıÂÓ›˜ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ¢O Î·È ÛÙÔ˘˜ 17 ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ÂÓ‰ÔÔÛÙÈΤ˜ Û˘Û΢¤˜, ÂÓÒ ÛÙÔ˘˜ ˘fiÏÔÈÔ˘˜ 13 Â͈ÔÛÙÈΤ˜. Afi ÙÔ Û‡ÓÔÏÔ ÙˆÓ 55 ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ Ô˘ ÙÔÔıÂÙ‹ıËÎ·Ó ÌÂÙ¿ ÙÔ Ù¤ÏÔ˜ Ù˘ ‰È¿Ù·Û˘ ·¤Ù˘¯·Ó Ù· 5, ‰È·ÌÔÚÊÒÓÔÓÙ·˜ ÙÔ ÔÛÔÛÙfi ÂÈÙ˘¯›·˜ ÛÙÔ 90,9%. T· 4 ·fi ·˘Ù¿ Ô˘ ·¤Ù˘¯·Ó ‚Ú›ÛÎÔÓÙ·Ó Û ÂÚÈÔ¯¤˜ fiÔ˘ ˘‹Ú¯Â ÌÂÁ¿ÏË ·ÔÚÚfiÊËÛË ÙÔ˘ ÎÈÓËÙÔ‡ ÎÔÏÔ‚ÒÌ·ÙÔ˜, ÂÓÒ ÙÔ ¿ÏÏÔ ¤Ó· ·¤Ù˘¯Â ÏfiÁˆ ÌfiÏ˘ÓÛ˘ ÙÔ˘ ¯ÂÈÚÔ˘ÚÁÈÎÔ‡ ‰›Ô˘. ™ÙËÓ ¤Ú¢ӷ ·˘Ù‹ ÌÂÏÂÙ‹ıËÎ·Ó Â›Û˘ ÔÈ ÂÈÏÔΤ˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Î·È ÌÂÙ¿ ÙÔ ¤Ú·˜ Ù˘ ‰È¿Ù·Û˘. OÈ ÂÈÏÔΤ˜ ‹Ù·Ó ΢ڛˆ˜ ÛÙÔ˘˜ Ì·Ï·ÎÔ‡˜ ÈÛÙÔ‡˜ (‰ËÌÈÔ˘ÚÁ›· ·‚·ıÔ‡˜ ÚÔÛÙÔÌ›Ô˘, ‰È¿ÓÔÈÍË ÙÔ˘ ÎÚËÌÓÔ‡ ÛÙȘ ı¤ÛÂȘ Ô˘ ‹Ù·Ó ÙÔÔıÂÙË̤Ó˜ ÔÈ ‰È·Ù·ÙÈΤ˜ Û˘Û΢¤˜), ̤ÙÚÈÔ ·ÈÛıËÙÈÎfi ·ÔÙ¤ÏÂÛÌ·, ‰˘ÛÎÔÏ›· ÚÔÛˆÚÈÓ‹˜ ·ÔηٿÛÙ·Û˘, ·ÛÙ¿ıÂÈ· Ù˘ Û˘Û΢‹˜, ÌfiÏ˘ÓÛË Î·ıÒ˜ Î·È ·ÔÚÚfiÊËÛË ÙÔ˘ ÎÈÓËÙÔ‡ ÎÔÏÔ‚ÒÌ·ÙÔ˜17. ™Â ÌÈ· ÂÚ¢ÓËÙÈ΋ ÌÂϤÙË, Ô˘ ¤ÁÈÓ ·fi ÙÔÓ Ettl Î·È Û˘Ó. ÙÔ 2010, ·ÍÈÔÏÔÁ‹ıËÎ·Ó ÔÈ ÂÈÏÔΤ˜ Ù˘ ‰È·‰Èηۛ·˜ Ù˘ ¢O ‰›ÓÔÓÙ·˜ ¤ÌÊ·ÛË ÛÙËÓ ÔÛÙÈ΋ ·ÔÚÚfiÊËÛË Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Ê¿Û˘ ÛÙ·ıÂÚÔÔ›ËÛ˘ Î·È Ù˘ Ê¿Û˘ ·Ó·‰È·ÌfiÚʈÛ˘ ÙÔ˘ ÔÛÙÔ‡ Û ‰Â›ÁÌ· 30 ÌÂÚÈÎÒ˜ Óˆ‰ÒÓ ·ÛıÂÓÒÓ. T· ·ÔÙÂϤÛÌ·Ù· ¤‰ÂÈÍ·Ó ˆ˜ Ë ÂÈ34 surgeon has the ability to clinically control and intervene during the entire alveolar bone augmentation. Additionally, the native bone creation in the defect area is significantly more effective compared to bone graft incorporation, even that if it is autogenous. Another advantage of DO comparing to autogenous bone graft is that there is no need for second surgical procedure at the donor area avoiding thus possible complications and additional postoperative discomfort of the patient. Finally, the fact that with this method, foreign origin materials can be avoided, is considered to be one of the main advantages of DO compared to other bone growth techniques, where xeno- or allografts are being used5-10. Among procedure’s disadvantages, there is a great risk of inferior alveolar nerve damage in cases where alveolar ridge height of mandible is needed. In addition, the use of transmucosal device can lead to the dehiscence of the wound and possible contamination of the area. If the device is placed in the anterior region creates an aesthetic problem in the patient. While, in any other position can create problems in talking, eating and difficulty in oral hygiene. Most of the distraction devices can achieve augmentation of the size of the jaw only at one level. Therefore, when besides height correction, jaw width adjustment is desired, it would be better to turn to other techniques. Finally, it can be mentioned that DO is a treatment with fairly high cost and requires surgical experience, whereas the satisfactory outcome is highly dependent on the complete patient’s cooperation7-9. In preprosthetic surgery, several studies have been mentioned in which distraction osteogenesis’s results have been compared to bone grafts. In 2004, Chiapasco et al., conducted a study to compare the clinical outcomes between the technique of DO and bone graft in deficient ridges with vertical bone deficiency. The study evaluated parameters such as bone absorption before and after the placement of the implants and the periimplant bone loss after one, two or three years of implants’ loading. The results showed that DO is a better technique as far as the integrity of periimplant bone is concerned11. An other study of Chiapasco et al., (2007) where techniques of autogenous bone grafts and DO were compared in total of 17 patients, showed that bone resorption before implant placement was significantly higher in the group with the autogenous bone grafts. On the contrary, no statistically significant differences were found between the two groups as far as survival and success rates of implants and peri-implant bone resorption after the loading of the implants12. Perez-Sayans et al., (2008) showed no difference in vertical absorption in distracted or in nondistracted bone, while the success rate of the implant was about the same in both techniques13. Uckan et al., (2008) studied the implant survival and complications rates during treatment after preprosthetic surgery comparing DO to autogenous onlay bone graft. Their results showed a higher complication rate in DO (66.8% versus 33.8%). However, the complications have been less severe and easier to Hellenic Stomatological Review 57: 27-37, 2013 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review ‚›ˆÛË ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ ÌÂÙ¿ ·fi ·Ú·ÎÔÏÔ‡ıËÛË 45,8 ÌËÓÒÓ ‹Ù·Ó 95,1%, ÂÓÒ Ù· ·ÚÈ· ÚÔ‚Ï‹Ì·Ù· Ô˘ ·ÓÙÈÌÂÙˆ›ÛıËÎ·Ó ·ÊÔÚÔ‡Û·Ó ÙËÓ ·Ó·Ú΋ ‰È¿Ù·ÛË ÙˆÓ Ì·Ï·ÎÒÓ ÈÛÙÒÓ Û ÔÛÔÛÙfi 43% Î·È ÙËÓ ÔÛÙÈ΋ ·ÔÚÚfiÊËÛË Û ÔÛÔÛÙfi 21,1 % ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË ÙÔÔı¤ÙËÛË ÙÔ˘ ÂÌÊ˘Ù‡̷ÙÔ˜18. Afi ÌÈ· Û˘ÛÙËÌ·ÙÈ΋ ·Ó·ÛÎfiËÛË ÙˆÓ Aghaloo Î·È Moy, Ë ÔÔ›· ·ÍÈÔÏfiÁËÛ ¿ÚıÚ· ‰ËÌÔÛÈÂ˘Ì¤Ó· ·fi ÙÔ 1980 ¤ˆ˜ ÙÔ 2005, ÚԤ΢„ 94,7% ÔÛÔÛÙfi ÂÈÙ˘¯›·˜ ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ Û ı¤ÛÂȘ Ô˘ ÚÔËÁÔ˘Ì¤Óˆ˜ ›¯·Ó ‰Â¯ı› ¢O T· ·ÓÙ›ÛÙÔȯ· ÔÛÔÛÙ¿ ‹Ù·Ó 92% ÁÈ· ·˘ÙÔÁÂÓ‹ Î·È ·˘ÙÔÁÂÓ‹/Û‡ÓıÂÙ· ÌÔۯ‡̷ٷ Î·È 81% ÁÈ· ·ÏÏÔÏ·ÛÙÈο ˘ÏÈο Î·È ·ÏÏÔÏ·ÛÙÈο ˘ÏÈο/ÍÂÓÔÌÔۯ‡̷ٷ19. H ÂÈ‚›ˆÛË ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ ÌÂÙ¿ ·fi ¢O ¤¯ÂÈ ÌÂÏÂÙËı› ÛÂ Â›Â‰Ô Û˘ÛÙËÌ·ÙÈ΋˜ ·Ó·ÛÎfiËÛ˘ Î·È ·fi ÙÔ˘˜ Saulacic Î·È Û˘Ó. ÙÔ 2007 fiÔ˘ ·ÍÈÔÏÔÁ‹ıËÎ·Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÎÏÈÓÈÎÒÓ ÂÚ¢ÓÒÓ Û¯ÂÙÈο Ì ÙË ¢O Î·È ‰È·ÈÛÙÒıËÎÂ Ë Û ÌÂÁ¿ÏÔ ‚·ıÌfi ˘ÂÚÔ¯‹ ¢O Û ۯ¤ÛË Ì ¿ÏϘ Ù¯ÓÈΤ˜. TÔ ÔÛÔÛÙfi ÂÈÙ˘¯›·˜ ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ Ô˘ ÙÔÔıÂÙ‹ıËÎ·Ó ÌÂÙ¿ ÙÔ Ù¤ÏÔ˜ Ù˘ ‰È·‰Èηۛ·˜ ·Ó¤Ú¯ÔÓÙ·Ó ÛÙÔ 97%20. ™Â ÌÈ· ÌÂϤÙË Ô˘ ¤ÁÈÓ ÛÙÔ ·ÓÂÈÛÙ‹ÌÈÔ Aarhus ·fi ÙÔ˘˜ Kristian Î·È Û˘Ó. (2004-2011) ·ÍÈÔÏÔÁ‹ıËÎ·Ó Ù· Èı·Ó¿ Û˘ÌÙÒÌ·Ù· Û 20 ·ÛıÂÓ›˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋˜ ÂÚÈfi‰Ô˘ Ô˘ ›¯·Ó ˘Ô‚ÏËı› Û ¢O ÛÙËÓ ¿Óˆ ÁÓ¿ıÔ Ì ÂÓ‰ÔÛÙÔÌ·ÙÈΤ˜ ‰È·Ù·ÙÈΤ˜ Û˘Û΢¤˜. T· ·ÔÙÂϤÛÌ·Ù· Ù˘ ¤Ú¢ӷ˜ ¤‰ÂÈÍ·Ó fiÙÈ ÙÔ 80% ÙˆÓ ·ÛıÂÓÒÓ Â›¯·Ó ÌÈÎÚ¤˜ ÂÓԯϋÛÂȘ, fiˆ˜ fiÓÔ˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ ‰È·Ù·ÙÈ΋˜ Û˘Û΢‹˜ Î·È ‰È¿ÊÔÚ˜ ÏÔÈÌÒÍÂȘ21. TÔ 2003, Ú·ÁÌ·ÙÔÔÈ‹ıËΠÌÈ· ¤Ú¢ӷ ·fi ÙÔ˘˜ Garcia-Garcia. Î·È Û˘Ó. Û ‰Â›ÁÌ· 7 ·ÛıÂÓÒÓ ÛÙËÓ Ô›ÛıÈ· ÂÚÈÔ¯‹ Ù˘ οو ÁÓ¿ıÔ˘ ÁÈ· ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Ù˘ ¢O Û ÌÂȈ̤ÓÔ ‡„Ô˜ ÔÛÙÈÎÔ‡ ˘ÔÛÙÚÒÌ·ÙÔ˜. T· ·ÔÙÂϤÛÌ·Ù¿ Ù˘ ¤‰ÂÈÍ·Ó fiÙÈ Ë ¢O ·ÔÙÂÏ› ÌÈ· ·ÔÙÂÏÂÛÌ·ÙÈ΋ Ù¯ÓÈ΋ ÁÈ· ÙËÓ ·‡ÍËÛË ÙÔ˘ ‡„Ô˘˜ ÙÔ˘ ÔÛÙÈÎÔ‡ ˘ÔÛÙÚÒÌ·ÙÔ˜ ÛÙËÓ Ô›ÛıÈ· ÂÚÈÔ¯‹ Ù˘ οو ÁÓ¿ıÔ˘ Î·È Û˘ÛÙ‹ÓÂÙ·È Ó· ÂÊ·ÚÌfi˙ÂÙ·È ÁÈ· ÙËÓ ‚ÂÏÙ›ˆÛË Ù˘ Ì˘ÏÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋˜ ·Ó·ÏÔÁ›·˜ fiÙ·Ó ·˘Ù‹ Â›Ó·È È‰È·›ÙÂÚ· ‰˘ÛÌÂÓ‹˜ ÏfiÁˆ Ù˘ οıÂÙ˘ ·ÔÚÚfiÊËÛ˘ ÙÔ˘ ÔÛÙÔ‡22. ¶ÚfiÛÊ·Ù· ÂÚ¢ÓËÙÈο ‰Â‰Ô̤ӷ ‰ËÌÔÛ›Â˘Û·Ó ÙÔ 2012 ÔÈ Yamauchi Î·È Û˘Ó. ÔÈ ÔÔ›ÔÈ ÂÊ¿ÚÌÔÛ·Ó ÙËÓ Ù¯ÓÈ΋ Ù˘ ‰È·Ù·ÙÈ΋˜ ÔÛÙÂÔÁ¤ÓÂÛ˘ Û 12 ·ÛıÂÓ›˜ Ì ÛÔ‚·Ú‹ ÔÚÈ˙fiÓÙÈ· ·ÙÚÔÊ›· ÌÂÚÈÎÒ˜ Óˆ‰‹˜ ÁÓ¿ıÔ˘ (¿Óˆ ‹ οو) Î·È ÛÙË Û˘Ó¤¯ÂÈ· ÙÔÔı¤ÙËÛ·Ó ÂÌÊ˘Ù‡̷ٷ. ⁄ÛÙÂÚ· ·fi ̤ÛÔ fiÚÔ ·Ú·ÎÔÏÔ‡ıËÛ˘ 5,4 ¯ÚfiÓÈ· Ù· ÔÛÔÛÙ¿ ÂÈ‚›ˆÛ˘ Î·È ÂÈÙ˘¯›·˜ ÙˆÓ ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ ‹Ù·Ó 100% ÛÙËÓ ¿Óˆ Î·È 94,2% ÛÙËÓ Î¿Ùˆ ÁÓ¿ıÔ23. ™˘ÌÂÚ·ÛÌ·ÙÈο Ë ¢È·Ù·ÙÈ΋ OÛÙÂÔÁ¤ÓÂÛË ·ÔÙÂÏ› Ì›· ·ÍÈfiÈÛÙË Ì¤ıÔ‰Ô ÔÛÙÈ΋˜ ·Ó¿Ï·Û˘ ÛÙËÓ ÚÔÂÌÊ˘ÙÂ˘Ì·ÙÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋. EӉ›ÎÓ˘Ù·È Û ̤ÙÚÈ· ‹ ÛÔ‚·Ú¿ ÔÛÙÈο ÂÏÏ›ÌÌ·Ù· ΢ڛˆ˜ ÛÙËÓ ÚfiÛıÈ· ÂÚÈÔ¯‹ Ù˘ οو ÁÓ¿ıÔ˘. TÔ Î‡ÚÈÔ ÏÂÔÓ¤ÎÙËÌ¿ Ù˘ Â›Ó·È Ë ‰È¿Ù·ÛË Î·È ÙˆÓ Ì·Ï·ÎÒÓ ÈÛÙÒÓ Ù·˘Ùfi¯ÚÔÓ· Ì ÙËÓ ÔÛÙÈ΋ ÂÓÒ ··ÈÙÂ›Ù·È È‰È·›ÙÂÚË ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÌÂÈÚ›· ·fi ÙÔÓ ÂÂÌ‚·›ÓÔÓÙ· Î·È Ë ·fiÏ˘ÙË Û˘ÓÂÚÁ·Û›· ÙÔ˘ ·ÛıÂÓÔ‡˜. Hellenic Stomatological Review 57: 27-37, 2013 manage with DO than those observed after treatment with autograft. In this study, the success rate of the implants was similar in both techniques (91.4% versus 93.7 DO graft)14. In 2005, Enislidis G. et al., conducted a retrospective study which evaluated complications before, during, and after horizontal alveolar distraction osteogenesis and assessed the survival rate of dental implants placed in distracted bone. Complications associated with the distraction procedure affected 75.7% of patients, but the majority of them were not significant and the implant survival was 95.7%15. On the other hand, Bianchi et al. (2008) showed that although the bone remodeling by DO techniques was significantly higher (10 mm instead of 5,8 mm), the complication rate was significantly greater in DO’ patients (60%) than those in the graft technique (14.3%)16. In 2008, Froum et al., published the results of a survey in which distraction procedures were performed in 30 patients using 17 intraosseous and 13 extraosseous devices. Of the overall of 55 implants placed after the distraction, 5 of them failed, so the success rate was 90.9%. The 4 of these failed in areas where there was a large absorption of the distracted segment, while the other one has failed due to contamination of the surgical field. This study also investigates the complications during and after distraction. Complications involving the soft tissues (diminished vestibule of the mouth, flap dehiscence), compromised aesthetic results, difficulties in transitional prosthesis, distractor instability, infection, and resorption of the transport segment17. In a retrospective study by Ettl et al. in 2010 the complications of DO with specific focus on bone resorption during the consolidation period and the follow-up period after dental implant insertion into distracted bone in a sample of 30 partially edentulous patients were evaluated. Treatment results showed a survival rate of 95.1% after 45.8 months, whereas the main problems were the inadequate soft tissue extension (43%) and mean resorption (21.1%) at the time of dental implant insertion18. According to a systematic review from Aghaloo and Moy which evaluated published articles between 1980 to 2005, implant survival was 94,7% for implants placed into bone which had previously been distracted. On the contrary implant survival rate was 92% for implants placed into autogenous and autogenous-composite grafts and 81% for implants placed into alloplast and alloplast-xenograft materials19. Implant survival rates after DO have also been studied in a systemic review from Saulacic et al. in 2007, where the outcomes of clinical studies referred to alveolar distraction osteogenesis have been analysed and it was found the superiority of DO compared to other techniques. The survival rate for implants placed after the end of the procedure was 97%20. Kristian et al., conducted a study, which took place in Aarhus university from 2004 up to 2011 and was 35 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review BIB§IO°PAºIA 1. Iatrou I, Theologie-Lygidakis N, Schoinohoriti O: Mandibular distraction osteogenesis for severe airway obstruction in Robin Sequence. Case report. J Craniomaxillofac Surg 2010 Sep; 38 (6): 431-5. doi: 10.1016/j.jcms. 2009.10.019. Epub 2009 Dec 11. 2. McCarthy J., Kerwin Williams J: Maxillofacial surgery, ‰Â‡ÙÂÚË ¤Î‰ÔÛË 2007 vol. 2, 959-980, St. Louis Missouri. 3. Lambrechut J, Filippi A, Hoffmeister B, Krevsh T, Wangerin K: Oral and implant surgery. Principles and procedures, Quintessence 2009, UK. 4. Bell WH, Guerrero CA: Distraction Osteogenesis of the Facial Skeleton BC Decker 2007. 5. Hupp JR, Ellis E, Tucker HR: Oral and maxillofacial surgery 5th edition, 2008, St. Louis Missouri. 6. Oda T, Sawaki Y, Ueda M: Experimental alveoral ridge augmentation distraction osteogenesis using a simple device that permits secondary implant placement, The International JÔurnal of Oral and Maxillofacial Implants 2000; 15 (1): 95-101. 7. Lster Z, Rachmiel A, Jensen O: Alveoral width distraction osteogenesis for early implant placemenet, J Oral Maxilofac Surg 2005; 63: 1724-1730. 8. Lster Z: Alveoral distraction osteogenesis- Crestal widening by distraction osteogenesis. Hellenic archives of oral and maxilloafacial surgery, 2010: 3-14. 9. Vega L, Bilbao A: Alveoral distraction osteogenesis for dental implant preparation. An update 2010: 370-383. 10. Jensen O: Alveoral Distraction Osteogenesis, Quintessence Publishing, 2002, China. 11. Chiapasco M, Consolo U, Bianchi A, Ronchi P: Alveolar distraction osteogenesis for the correction of vertically deficient edentulous ridges: a multicenter prospective study on humans. Int J Oral Maxillofac Implants 2004; 19 (3): 399-407. 12. Chiapasco M, Zaniboni M, Rimondini L: Autogenous onlay bone grafts vs. alveolar distraction osteogenesis for the correction of vertically deficient edentulous ridges: a 2-4year prospective study on humans. Clin Oral Implants Res 2007; 18 (4): 432-440. 13. Perez-Sayans M, Fernandez-Gonzalez B, Somoza-Martin ’ M, Gandara-Rey JM, Garc›a-Garc›a: A Peri-implant bone resorption around implants placed in alveolar bone subjected to distraction osteogenesis. J Oral Maxillofac Surg 2008; 66 (4): 787-790. 14. Uckan S, Oguz Y, Bayram B: Comparison of intraosseous and extraosseous alveoral distraction osteogenesis. J Oal Maxillofac Surg 2007; 65 (4): 671- 674. 15. Enislidis G, Fock N, Millesi-Schobel G, Klug C, Wittwer G, Yerit K, Ewers R: Analysis of complications following alveoral distraction osteogenesis and implant placement in the partially edentulous mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005 Jul; 100 (1): 25-30. 16. Bianchi A, Felice P, Lizio G, Marchetti C: Alveolar distraction osteogenesis versus inlay bone grafting in posterior mandibular atrophy: a prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008 Mar; 105 (3): 282-292. 17. Froum SJ, Rosenberg ES, Elian N, Tarnow D, Choon Cho S: Distraction Osteogenesis for Ridge Augmentation: Prevention and Treatment of Complications. Thirty Case Reports. Int J Periodontics Restorative Dent 2008; 28: 337-345. 18. Ettl T, Gerlach T, Schüsselbauer T, Gosau M, Reichert TE, Driemel O: Bone resorption and complications in alveolar distraction osteogenesis. Clin Oral Investig 2010; 14 (5): 481-489. 19. Aghaloo TL, Moy PK: Which hard tissue augmentation techni36 assessed the frequency and distribution of incidents in 20 patients encountered during the perioperative period of maxillary distraction with internal devices. The results of the study have shown that 80% of the patients experienced minor incidents, of which the most frequent were pain during activation and infections21. In 2003, a study took place from Garcia-Garcia et al., in seven patients, where the efficacy of DO in cases of reduced crown height in the posterior mandible was investigated. The results showed that alveolar DO is an effective technique for increasing the height of the alveolar ridge in the posterior mandibular region, and should be considered for the improvement of a negative crown to implant ratio in severely absorbed areas22. Recent research data have been published in 2012, by Yamauchi et al, who treated 12 patients with severe horizontal atrophy of a partially edentulous maxillas or mandibles using horizontal DO for implant placement. After mean follow-up of 5.4 years. the implant survival and success rates were 100% and 94.2%, respectively23. Conclusively, Distraction Osteogenesis is a reliable method of bone regeneration in pre-implant surgery. It is mainly indicated in moderate or severe bone loss mainly in the anterior region of the mandible. Its main advantage is the distraction of the soft tissues and bone at the same time, whereas special surgical experience and full cooperation of the patient is required. Contact details: Fotios Tzermpos e-mail: [email protected] Hellenic Stomatological Review 57: 27-37, 2013 ∂ӉȷʤÚÔ˘Û· ¶ÂÚ›ÙˆÛË Case report and literature review ques are the most successful in furnishing bony support for implant placement?: Int J Oral Maxillofac Implants 2007; 22 Suppl: 49-70. 20. Saulacic N, Iizuka T, Martin MS, Garcia AG: Alveolar distraction osteogenesis: a systematic review. Int J Oral Maxillofac Surg 2008; 37 (1): 1-7. 21. Kristian A, Erik NS, Annelise K, John J, Klit PT: Perioperative incidents associated with internal maxillary distraction osteogenesis: a retrospective study of 20 patients. Oral Surg Oral Med Oral Pathol Oral Radiol 2012 Aug 15-25 [Epub ahead of print]. 22. Garcia-Garcia A, Somoza-Martin M, Gandara-Vila P, Saulacic N, Gandara-Rey JM: Alveolar distraction before insertion of dental implants in the posterior mandible. Br J Oral Maxillofac Surg 2003 Dec; 41 (6): 376-379. 23. Yamauchi K, Takahashi T, Nogami S, Kataoka Y, Miyamoto I, Funaki K: Horizontal alveolar distraction osteogenesis for dental implant: long-term results. Clin Oral Implants Res 2012 Jan 26. doi: 10.1111/j.1600-0501.2011.02417.x. [Epub ahead of print]. ¢È‡ı˘ÓÛË ÁÈ· ÂÈÎÔÈÓˆÓ›·: ºÒÙÈÔ˜ Δ˙¤ÚÌÔ˜ e-mail: [email protected] Hellenic Stomatological Review 57: 27-37, 2013 37 BÈ‚ÏÈÔÁÚ·ÊÈ΋ AÓ·ÛÎfiËÛË Literature Review MÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Î·È ÌÂÙ·ÊÔÚ¿ ÁÔÓȉ›ˆÓ ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ £. KÔÓ‰‡Ï˘*, E. ¶ÂÂÏ¿ÛË** Mesenchymal stem cell transplantation and gene transfer for periodontal tissue regeneration T. Kondylis*, E. Pepelassi** ¶EPI§HæH SUMMARY H ÂÈÙ˘¯›· ÙˆÓ ·Ó·Ï·ÛÙÈÎÒÓ Ù¯ÓÈÎÒÓ ÛÙȘ ÂÚÈÔ‰ÔÓÙÈΤ˜ ÂÓ‰ÔÛÙÈΤ˜ ‚Ï¿‚˜ ÂËÚ¿˙ÂÙ·È ·fi ÙË ÌÔÚÊÔÏÔÁ›· Ù˘ ÔÛÙÈ΋˜ ‚Ï¿‚˘ Î·È Ù· ·Ó·Ï·ÛÙÈο ̤۷ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È. ¶ÚfiÛÊ·Ù· ¤¯ÂÈ ·Ú¯›ÛÂÈ Ó· ÌÂÏÂÙ¿Ù·È Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Î·È Ë ÌÂÙ·ÊÔÚ¿ ÁÔÓȉ›ˆÓ ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Ì ÂÓı·ÚÚ˘ÓÙÈο ·ÔÙÂϤÛÌ·Ù·. T· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· Ó· ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û ·ÙÙ·Ú· ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î·È Û˘Ó‰ÂÙÈÎÒÓ ÈÛÙÒÓ. £· ÌÔÚÔ‡Û·Ó Ó· Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Â›Ù ·ÂÏ¢ıÂÚÒÓÔÓÙ·˜ ·˘ÍËÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ‰ÚÔ˘Ó Û ÂÓ‰ÔÁÂÓ‹ ·ÙÙ·Ú· ‹ ÔÏÏ·Ï·ÛÈ·˙fiÌÂÓ· Î·È ‰È·ÊÔÚÔÔÈÔ‡ÌÂÓ· Û ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÔ‰ÔÓÙ›Ô˘. H ÌÂÙ·ÊÔÚ¿ ÁÔÓȉ›ˆÓ Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ıÂڷ¢ÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Û ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÔ‰ÔÓÙ›Ô˘ ÚÔÛʤÚÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ¤ÎÊÚ·Û‹˜ ÙÔ˘˜ ÁÈ· ÌÂÁ·Ï‡ÙÂÚÔ The success of the regenerative techniques in periodontal defects depends on the osseous defect morphology and the regenerative means used. Recently, the study of mesenchymal stem cell transplantation and gene transfer for periodontal regeneration has been initiated with encouraging results. Mesenchymal stem cells have the ability to differentiate into cells of mesenchymal and connective tissues. They might help in periodontal regeneration either by releasing growth factors acting on endogenous cells or by proliferating and differentiating into cells of the periodontium. Transferring genes that encode therapeutic agents to periodontal cells offers the possibility of longer expression than local application does, expression of a combination of therapeutic agents and time-controlled expression in correspondence to the tissue healing process. The first purpose of the present literature review was * O‰ÔÓÙ›·ÙÚÔ˜ ** E›ÎÔ˘ÚË K·ıËÁ‹ÙÚÈ·, EÚÁ·ÛÙ‹ÚÈÔ ¶ÂÚÈÔ‰ÔÓÙÔÏÔÁ›·˜, O‰ÔÓÙÈ·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ AıËÓÒÓ ÂÏÏËÓÈο ÛÙÔÌ·ÙÔÏÔÁÈο ¯ÚÔÓÈο 57: 39-71, 2013 ·ÚÂÏ‹ÊıË 29/4/2013 - ÂÎÚ›ıË 11/6/2013 * Dentist ** Assistant Professor, Department of Periodontology, University of Athens School of Dentistry Hellenic Stomatological Review 57: 39-71, 2013 paper received 29/4/2013 - accepted 11/6/2013 39 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ‰È¿ÛÙËÌ· Û ۇÁÎÚÈÛË Ì ÙËÓ ÙÔÈ΋ ÂÊ·ÚÌÔÁ‹, ¤ÎÊÚ·Û˘ Û˘Ó‰˘·ÛÌÔ‡ ÂÚÈÛÛfiÙÂÚˆÓ ·Ú·ÁfiÓÙˆÓ Î·È ¯ÚÔÓÈο ÂÏÂÁ¯fiÌÂÓ˘ ¤ÎÊÚ·Û˘ ·ÓÙ›ÛÙÔȯ· Ì ÙȘ ‰ÈÂÚÁ·Û›Â˜ ÂԇψÛ˘ ÙˆÓ ÈÛÙÒÓ. O ÚÒÙÔ˜ ÛÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ‚È‚ÏÈÔÁÚ·ÊÈ΋˜ ·Ó·ÛÎfiËÛ˘ ‹Ù·Ó Ë ·Ó¿Ï˘ÛË ÙˆÓ ÌÂÏÂÙÒÓ Ô˘ ·ÊÔÚÔ‡Ó ÛÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÛÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ, ÙËÓ ·ÛÊ¿ÏÂÈ· Ù˘ Ù¯ÓÈ΋˜ ÁÈ· ÙÔÓ ‰¤ÎÙË ÔÚÁ·ÓÈÛÌfi Î·È ÙËÓ Â›‰Ú·ÛË Ù˘ ÚÔ¤Ï¢Û˘ ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Î·È ÙÔ˘ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ Ù˘ ‰¤ÎÙÚÈ·˜ ÂÚÈÔ¯‹˜ ÛÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi Î·È ÙË ‰È·ÊÔÚÔÔ›ËÛË ÙÔ˘˜. O ‰Â‡ÙÂÚÔ˜ ÛÎÔfi˜ Ù˘ ·Ó·ÛÎfiËÛ˘ ‹Ù·Ó Ë ·Ó¿Ï˘ÛË ÙˆÓ ÌÂÏÂÙÒÓ Ô˘ ·ÊÔÚÔ‡Ó ÛÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ ÌÂÙ·ÊÔÚ¿˜ ÁÔÓȉ›ˆÓ ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ, ÔÈ ÙÚfiÔÈ ÌÂÙ·ÊÔÚ¿˜ ÙÔ˘˜ Î·È Ë ·ÛÊ¿ÏÂÈ· Ù˘ Ù¯ÓÈ΋˜. §¤ÍÂȘ ÎÏÂȉȿ: ΢ÙÙ·ÚÈ΋ ıÂڷ›·, ÁÔÓȉȷ΋ ıÂڷ›·, ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ, ÌÂÙ·ÊÔÚ¿ ÁÔÓȉ›ˆÓ, ÂÚÈÔ‰ÔÓÙ›Ùȉ·, ·Ó¿Ï·ÛË ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ. EI™A°ø°H H ÂÚÈÔ‰ÔÓÙ›Ùȉ· Â›Ó·È ÌÈ· ¯ÚfiÓÈ· ÊÏÂÁÌÔÓ҉˘ ÓfiÛÔ˜ ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ ÌÈÎÚԂȷ΋˜ ·ÈÙÈÔÏÔÁ›·˜. H ıÂڷ¢ÙÈ΋ ÚÔÛ¤ÁÁÈÛË Ù˘ ÂÚÈÔ‰ÔÓÙ›Ùȉ·˜ ·ÔÛÎÔ› ÛÙËÓ ·Ó·¯·›ÙÈÛË Ù˘ ÂͤÏÈ͢ Ù˘ ÓfiÛÔ˘ Î·È ÛÙËÓ Î·Ù¿ ÙÔ ‰˘Ó·ÙfiÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Ô˘ ¤¯Ô˘Ó ·ˆÏÂÛı› ÏfiÁˆ Ù˘ ÓfiÛÔ˘. OÈ ¯ÂÈÚÔ˘ÚÁÈΤ˜ Ù¯ÓÈΤ˜ Ô˘ ¤¯Ô˘Ó ·Ó·Ù˘¯ı› ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙËÓ Î·Ù¢ı˘ÓfiÌÂÓË ÈÛÙÈ΋ ·Ó¿Ï·ÛË, Ù· ÔÛÙÈο ÌÔۯ‡̷ٷ, ÙÔ˘˜ ‚ÈÔÏÔÁÈÎÔ‡˜ ÌÂÛÔÏ·‚ËÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Î·È ÙÔ Û˘Ó‰˘·ÛÌfi ·˘ÙÒÓ. OÈ ·Ó·Ï·ÛÙÈΤ˜ Ù¯ÓÈΤ˜ ÂÊ·ÚÌfi˙ÔÓÙ·È ÌfiÓÔ Û ÂÚÈÔ¯¤˜ Ì ÁˆÓÈÒ‰Ë ·ÒÏÂÈ· ÔÛÙÔ‡ Î·È ÂÓ‰ÔÛÙÈΤ˜ ‚Ï¿‚˜1. H ÂÈÙ˘¯›· ·˘ÙÒÓ ÙˆÓ Ù¯ÓÈÎÒÓ ÂËÚ¿˙ÂÙ·È ÛËÌ·ÓÙÈο ·fi ÙË ÌÔÚÊÔÏÔÁ›· Ù˘ ÂÓ‰ÔÛÙÈ΋˜ ‚Ï¿‚˘ Î·È Ù· ·Ó·Ï·ÛÙÈο ̤۷ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È2. ŸÛÔÓ ·ÊÔÚ¿ ÛÙË ÌÔÚÊÔÏÔÁ›· Ù˘ ÔÛÙÈ΋˜ ‚Ï¿‚˘, Ë ÂÈÙ˘¯›· ÙˆÓ ·Ó·Ï·ÛÙÈÎÒÓ Ù¯ÓÈÎÒÓ Â›Ó·È ˘„ËÏfiÙÂÚË Û ÂÓ‰ÔÛÙÈΤ˜ ‚Ï¿‚˜ ÙÚÈÒÓ ÔÛÙÈÎÒÓ ÙÔȯˆÌ¿ÙˆÓ, ÛÙȘ Ôԛ˜ ÙÔ ÂÓ‰ÔÛÙÈÎfi ÙÌ‹Ì· Ô˘ ÂÚÈ‚¿ÏÏÂÙ·È ·fi ÙÚ›· ÔÛÙÈο ÙÔȯÒÌ·Ù· ¤¯ÂÈ ‚¿ıÔ˜ ÙÔ˘Ï¿¯ÈÛÙÔÓ 3 mm ηıÒ˜ Î·È Û ‚Ï¿‚˜ Ù˘ ÂÚÈÔ¯‹˜ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÚÈ˙ÒÓ Î·ÙËÁÔÚ›·˜ II. ™Â ‚Ï¿‚˜ Ù˘ ÂÚÈÔ¯‹˜ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÚÈ˙ÒÓ Î·ÙËÁÔÚ›·˜ III Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ·˘ÙÒÓ ÙˆÓ Ù¯ÓÈÎÒÓ Â›Ó·È ÙfiÛÔ ¯·ÌËÏ‹ ÒÛÙ ·˘Ù¤˜ ‰ÂÓ ÂÊ·ÚÌfi˙ÔÓÙ·È2. ¶ÚfiÛÊ·Ù·, ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ ¤¯ÂÈ ·Ú¯›ÛÂÈ Ó· ÌÂÏÂÙ¿Ù·È Ë Î˘ÙÙ·ÚÈ΋ Î·È Ë ÁÔÓȉȷ΋ ıÂڷ›·. ø˜ ΢ÙÙ·ÚÈ΋ ıÂڷ›· ÔÚ›˙ÂÙ·È Ë ıÂڷ›· ÌÈ·˜ ÓfiÛÔ˘ ‹ ηٿÛÙ·Û˘ Ì ÙË ÌÂÙ·ÊÔÚ¿ Ó¤ˆÓ ΢ÙÙ¿ÚˆÓ Û ¤Ó·Ó ÈÛÙfi. ŸÛÔÓ ·ÊÔÚ¿ ÛÙËÓ ıÂڷ›· Ù˘ ÂÚÈÔ‰ÔÓÙ›ÙÈ40 the analysis of the studies concerning the use of mesenchymal stem cell transplantation in periodontal regeneration and the safety of the technique as well as the effect of cell origin and recipient site environment on their proliferation and differentiation. The second purpose of this review was the analysis of the studies concerning the use of gene transfer in periodontal regeneration, the transferring modes and the safety of the technique. Key Words: cell therapy, gene therapy, mesenchymal stem cell transplantation, gene transfer, periodontits, periodontal tissue regeneration. INTRODUCTION Periodontitis is a chronic inflammatory disease of the periodontal tissues, of microbial etiology. The aim of the periodontal treatment is to restrain the progression of the periodontal disease and regenerate the lost periodontal tissues, whenever possible. The surgical techniques that have been used for the regeneration of the periodontal tissues include the guided tissue regeneration, the osseous grafts, the biologic mediators of the regeneration and the combination of these techniques. Regenerative techniques are used only in areas with angular bone loss and intraosseous defects1. Their success is significantly affected by the morphology of the intraosseous defect and the regenerative means used2. Concerning the morphology of the osseous defect, the success of the regenerative techniques is highest for three-wall intraosseous defects, where the three-wall part of the defect is at least 3mm deep, as well as for class II furcation defects. The effectiveness of the regenerative techniques is so low for class III furcation defects that they are not used in such defects2. Recently, cell-based therapy and gene therapy have been studied for the regeneration of the periodontal tissues. Cell-based therapy is defined as the treatment of a disease or condition by transferring new cells into a tissue. Concerning cell-based therapy in periodontitis, the new cells transferred to the periodontal tissues might help in the regeneration of the periodontal tissues either by releasing growth factors that act on endogenous cells or by proliferating and differentiating into cells of the periodontium, irrespective of endogenous cells3, 4. Such cells are stem cells, which have the ability to proliferate and differentiate into progenitor cells5. Gene therapy is defined as the treatment of a disease or condition by transferring genetic material that aims to introduce, suppress or manipulate specific genes that direct the target-cells of the host to the production of a therapeutic agent6. Gene therapy is advantageous over local application of therapeutic agents. The duration of the expression of genes encoding therapeutic agents ranges from weeks to years while the half-life of locally Hellenic Stomatological Review 57: 39-71, 2013 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ‰·˜, Ù· Ó¤· ·ÙÙ·Ú· Ô˘ ÌÂٷʤÚÔÓÙ·È Ì ÙËÓ Î˘ÙÙ·ÚÈ΋ ıÂڷ›· ÛÙÔ˘˜ ÂÚÈÔ‰ÔÓÙÈÎÔ‡˜ ÈÛÙÔ‡˜ ı· ÌÔÚÔ‡Û·Ó Ó· Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Â›Ù ·ÂÏ¢ıÂÚÒÓÔÓÙ·˜ ·˘ÍËÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ‰ÚÔ˘Ó Û ÂÓ‰ÔÁÂÓ‹ ·ÙÙ·Ú· ‹ ÔÏÏ·Ï·ÛÈ·˙fiÌÂÓ· Î·È ‰È·ÊÔÚÔÔÈÔ‡ÌÂÓ· Û ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÔ‰ÔÓÙ›Ô˘, ·ÓÂÍ¿ÚÙËÙ· ·fi Ù· ÂÓ‰ÔÁÂÓ‹ ·ÙÙ·Ú·3, 4. T¤ÙÔÈ· ·ÙÙ·Ú· Â›Ó·È Ù· ‚Ï·ÛÙÔ·ÙÙ·Ú·, Ô˘ ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· Ó· ÔÏÏ·Ï·ÛÈ¿˙ÔÓÙ·È Î·È Ó· ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û ÚÔÁÔÓÈο ·ÙÙ·Ú·5. ø˜ ÁÔÓȉȷ΋ ıÂڷ›· ÔÚ›˙ÂÙ·È Ë ıÂڷ›· ÌÈ·˜ ÓfiÛÔ˘ ‹ ηٿÛÙ·Û˘ Ì ÙË ÌÂÙ·ÊÔÚ¿ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ Ô˘ ·ÔÛÎÔ› ÛÙËÓ ÂÈÛ·ÁˆÁ‹, ηٷÛÙÔÏ‹ ‹ ‰È·¯Â›ÚÈÛË Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ÁÔÓȉ›ˆÓ Ô˘ ηÙ¢ı‡ÓÔ˘Ó Ù· ·ÙÙ·Ú·-ÛÙfi¯Ô˘˜ ÙÔ˘ ÍÂÓÈÛÙ‹ ÛÙËÓ ·Ú·ÁˆÁ‹ ÂÓfi˜ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ ıÂڷ¢ÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·6. H ÁÔÓȉȷ΋ ıÂڷ›· ÏÂÔÓÂÎÙ› ¤Ó·ÓÙÈ Ù˘ ÙÔÈ΋˜ ÂÊ·ÚÌÔÁ‹˜ Ê·ÚÌ·ÎÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ. H ‰È¿ÚÎÂÈ· ¤ÎÊÚ·Û˘ ÙˆÓ ÁÔÓȉ›ˆÓ Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ıÂڷ¢ÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Î˘Ì·›ÓÂÙ·È ·fi ‚‰ÔÌ¿‰Â˜ ¤ˆ˜ ¯ÚfiÓÈ· ÂÓÒ Ô ¯ÚfiÓÔ˜ ËÌ›ÛÂÈ·˜ ˙ˆ‹˜ ÙˆÓ ÙÔÈο ÂÊ·ÚÌÔ˙fiÌÂÓˆÓ Ê·ÚÌ·ÎÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Â›Ó·È Ôχ ÌÈÎÚfiÙÂÚÔ˜ Î·È Û˘Ó‹ıˆ˜ Î˘Ì·›ÓÂÙ·È ·fi ÒÚ˜ ¤ˆ˜ Ë̤Ú˜. EÈϤÔÓ, Ë ÁÔÓȉȷ΋ ıÂڷ›· ÚÔÛʤÚÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ¤ÎÊÚ·Û˘ Û˘Ó‰˘·ÛÌÔ‡ ÂÚÈÛÛfiÙÂÚˆÓ ÙÔ˘ ÂÓfi˜ ıÂڷ¢ÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ. H ¤ÎÊÚ·ÛË ·˘Ù‹ ÌÔÚ› Ó· Â›Ó·È ¯ÚÔÓÈο ÂÏÂÁ¯fiÌÂÓË ·ÓÙ›ÛÙÔȯ· Ì ÙȘ ‰ÈÂÚÁ·Û›Â˜ ÂԇψÛ˘ ÙˆÓ ÈÛÙÒÓ3. KYTTAPIKH £EPA¶EIA T·ÍÈÓfiÌËÛË ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ T· ‚Ï·ÛÙÔ·ÙÙ·Ú· Ì ‚¿ÛË ÙËÓ ÚÔ¤ÏÂ˘Û‹ ÙÔ˘˜ ‰È·ÎÚ›ÓÔÓÙ·È Û ÂÌ‚Ú˘˚ο Î·È ÂÓ‹ÏÈη. T· ÂÌ‚Ú˘˚ο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙËÓ ÂÛˆÙÂÚÈ΋ ΢ÙÙ·ÚÈ΋ ÛÙÈ‚¿‰· Ù˘ ‚Ï·ÛÙÔ·ÛÙ˘ ÚÈÓ ÙËÓ ÂÌʇÙÂ˘Û‹ Ù˘ ÛÙË Ì‹ÙÚ· (ÂÌ‚Ú˘Ô‚Ï¿ÛÙË), Ô˘ ·ÔÙÂÏ› ÙËÓ Î·Ù·‚ÔÏ‹ ÙÔ˘ ÂÌ‚Ú‡Ô˘. T· ÂÓ‹ÏÈη ‚Ï·ÛÙÔ·ÙÙ·Ú· ÂÓÙÔ›˙ÔÓÙ·È ÛÙÔ˘˜ ÂÚÈÛÛfiÙÂÚÔ˘˜ ÈÛÙÔ‡˜ Î·È fiÚÁ·Ó· Î·È Û ÂÚ›ÙˆÛË ‚Ï¿‚˘ ÌÂÙ·Ó·ÛÙÂ‡Ô˘Ó ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ ‚Ï¿‚˘ Î·È Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ·ÔηٿÛÙ·Û‹ Ù˘7, 8. T· ‚Ï·ÛÙÔ·ÙÙ·Ú· Ù·ÍÈÓÔÌÔ‡ÓÙ·È Ì ‚¿ÛË ÙËÓ ÈηÓfiÙËÙ· ‰È·ÊÔÚÔÔ›ËÛ‹˜ ÙÔ˘˜ Û ÔÏÔ‰‡Ó·Ì·, ÔÈÎÈÏÔ‰‡Ó·Ì·, ÔÏ˘‰‡Ó·Ì·, ÔÏÈÁÔ‰‡Ó·Ì· Î·È ÌÔÓÔ‰‡Ó·Ì·. T· ÔÏÔ‰‡Ó·Ì· ·ÙÙ·Ú· ÌÔÚÔ‡Ó ÌÂÙ¿ ·fi ÂÌʇÙÂ˘Û‹ ÙÔ˘˜ ÛÙËÓ Ì‹ÙÚ· ˙ˆÓÙ·ÓÔ‡ ÔÚÁ·ÓÈÛÌÔ‡ Ó· ‰ÒÛÔ˘Ó Á¤ÓÂÛË Û ¤Ó·Ó Ó¤Ô ÔÚÁ·ÓÈÛÌfi. T· ÔÈÎÈÏÔ‰‡Ó·Ì· ·ÙÙ·Ú· ÌÔÚÔ‡Ó Ó· ·Ú¿ÁÔ˘Ó fiÏ· Ù· ·ÙÙ·Ú· ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ·ÏÏ¿ fi¯È Â͈ÂÌ‚Ú˘˚ÎÔ‡˜ ÈÛÙÔ‡˜, fiˆ˜ ÙÔÓ Ï·ÎÔ‡ÓÙ·. T¤ÙÔÈ· ·ÙÙ·Ú· Â›Ó·È Ù· ÂÌ‚Ú˘˚ο ‚Ï·ÛÙÔ·ÙÙ·Ú·. ¶ÔÈÎÈÏÔ‰‡Ó·Ì· ·ÙÙ·Ú· ÌÔÚÔ‡Ó Ó· ‰ËÌÈÔ˘ÚÁËıÔ‡Ó Î·È ÌÂÙ¿ ·fi ÂÈÛ·ÁˆÁ‹ Û ۈ̷ÙÈο ·ÙÙ·Ú· Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ÁÔÓȉ›ˆÓ, fiˆ˜ ÙˆÓ Oct-4, Sox2, c-Myc Î·È Klf4. T· ·ÙÙ·Ú· ·˘Ù¿ ÔÓÔÌ¿˙ÔÓÙ·È Â·¯ı¤ÓÙ· ÔÈÎÈÏÔ‰‡Ó·Ì· ·ÙÙ·Ú·. T· ÔÏ˘‰‡Ó·Ì· ·ÙÙ·Ú· ÌÔÚÔ‡Ó Ó· ·Ú¿ÁÔ˘Ó Î‡ÙÙ·Ú· Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ Î˘ÙÙ·ÚÈÎÒÓ ÛÂÈÚÒÓ. T¤ÙÔÈ· ·ÙÙ·Ú· Â›Ó·È Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú·. T· ÔÏÈÁÔ‰‡Ó·Ì· ·ÙÙ·Ú· ÌÔÚÔ‡Ó Ó· ‰È·ÊÔÚÔÔÈËıÔ‡Ó Û ϛÁÔ˘˜ Ù‡Ô˘˜ ΢ÙÙ¿ÚˆÓ Î·È Ù· ÌÔÓÔ‰‡Ó·Ì· ÌfiÓÔ Û ¤Ó·Ó7, 8. Hellenic Stomatological Review 57: 39-71, 2013 applied pharmacologic agents ranges from hours to days. Furthermore, gene therapy offers the possibility to express a combination of therapeutic agents. This expression can be time-controlled, in correspondence to the healing process3. CELL-BASED THERAPY Classification of stem cells Based on their origin, stem cells are classified into embryonic and adult. Embryonic stem cells originate from the blastocyst, the inner cell layer of the embryoblast, prior to implantation in the uterus, which comprises the ascend of the embryo. Adult stem cells are located in most tissues and organs and in case of damage they migrate to the damaged area and help restoring it7, 8. Based on the ability to differentiate, stem cells are classified into totipotent, pluripotent, multipotent, oligopotent and unipotent. Totipotent cells after implantation in the uterus of a living organism can give birth to a new organism. Pluripotent cells can produce all cells of the organism except from extra-embryonic tissues, such as the placenta. Embryonic stem cells belong to this cell group. Pluripotent cells can be created by introducing certain genes, such as Oct-4, Sox2, c-Myc and Klf4, into somatic cells. These cells are called induced pluripotent cells. Multipotent cells, such as mesenchymal stem cells, produce cells of specific lineages. Oligopotent cells differentiate into a few cell types, whereas unipotent cells differentiate only into one cell type7, 8. Mesenchymal stem cells Mesenchymal stem cells are adult stem cells that have the capacity to differentiate into cells of mesenchymal and connective tissues. Mesenchymal stem cells have been isolated from spleen, thymus, trabecular bone, bone marrow, periosteum, articular cartilage, synovium, synovial fluid, skeletal muscle, tendons, adipose tissue, blood and blood vessels. Moreover, they have been isolated from dental and periodontal tissues, namely the periodontal ligament, the dental pulp and the dental bud3, 7, 8. Cells have to fulfill a number of minimal criteria in order to be considered as mesenchymal stem cells. Table 1 presents the minimal criteria for the definition of cells as mesenchymal stem cells, as proposed by the International Society for Cellular Therapy9. Transplantation of mesenchymal stem cells in periodontal defects Mesenchymal stem cell transplantation for periodontal tissue regeneration has been extensively studied in animal models. Transplantation of mesenchymal stem cells, derived from dental and periodontal tissues, bone marrow and adipose tissue, into periodontal defects of animal models, by using various vehicles, has demonstrated encouraging results (Table 2). The evaluation of mesenchymal stem cell transplantation 41 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Table 1: Minimal criteria for the definition of cells as mesenchymal stem cells9 Criteria Detailed description Adherence to plastic Adherence to plastic when cultured under certain conditions and in certain flasks. Expression of specific surface antigens At least 95% of the population expresses CD105, CD73 and CD90 markers and less than 2% of the population CD45, CD34, CD14 or CD11b, CD79a or CD19 markers and HLA class II. Potential of multipotentdifferentiation Differentiation into 3 cell lineages, osteoblasts, adipocytes and chondroblasts under specific in-vitro conditions. MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· T· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Â›Ó·È ÂÓ‹ÏÈη ‚Ï·ÛÙÔ·ÙÙ·Ú· Ô˘ ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· Ó· ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û ·ÙÙ·Ú· ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î·È Û˘Ó‰ÂÙÈÎÒÓ ÈÛÙÒÓ. MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ¤¯Ô˘Ó ·ÔÌÔÓˆı› ·fi ÙÔÓ ÛÏ‹Ó·, ÙÔÓ ı‡ÌÔ, ÙÔ ÛÔÁÁ҉˜ ÔÛÙÔ‡Ó, ÙÔ Ì˘ÂÏfi ÙˆÓ ÔÛÙÒÓ, ÙÔ ÂÚÈfiÛÙÂÔ, ÙÔÓ ·ÚıÚÈÎfi ¯fiÓ‰ÚÔ, ÙËÓ ·ÚıÚÈ΋ ÌÂÌ‚Ú¿ÓË, ÙÔ ·ÚıÚÈÎfi ˘ÁÚfi, ÙÔ˘˜ ÛÎÂÏÂÙÈÎÔ‡˜ ̇˜, ÙÔ˘˜ Ù¤ÓoÓÙ˜, ÙÔ ÏÈÒ‰Ë ÈÛÙfi, ÙÔ ·›Ì· Î·È Ù· ·ÁÁ›·. Œ¯Ô˘Ó, ›Û˘, ·ÔÌÔÓˆı› ·fi Ô‰ÔÓÙÈÎÔ‡˜ Î·È ÂÚÈÔ‰ÔÓÙÈÎÔ‡˜ ÈÛÙÔ‡˜, Û˘ÁÎÂÎÚÈ̤ӷ ÙÔ ÂÚÈÚÚ›˙ÈÔ, ÙÔÓ Ô‰ÔÓÙÈÎfi ÔÏÊfi Î·È ÙÔ Ô‰ÔÓÙÔı˘Ï¿ÎÈÔ3, 7, 8. ¶ÚÔÎÂÈ̤ÓÔ˘ Û˘ÁÎÂÎÚÈ̤ӷ ·ÙÙ·Ú· Ó· ıˆÚËıÔ‡Ó ˆ˜ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ú¤ÂÈ ·˘Ù¿ Ó· ÏËÚÔ‡Ó ÔÚÈṲ̂ӷ ÂÏ¿¯ÈÛÙ· ÎÚÈÙ‹ÚÈ·. H ¢ÈÂıÓ‹˜ EÙ·ÈÚ›· K˘ÙÙ·ÚÈ΋˜ £Âڷ›·˜ ¤¯ÂÈ ıÂÛ›ÛÂÈ Ù· ÂÏ¿¯ÈÛÙ· ÎÚÈÙ‹ÚÈ· ÁÈ· ÙÔÓ ÔÚÈÛÌfi Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ ˆ˜ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ9. T· ÎÚÈÙ‹ÚÈ· ·˘Ù¿ Ê·›ÓÔÓÙ·È ÛÙÔÓ ›Ó·Î· 1. MÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Û ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ H ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ ¤¯ÂÈ ÌÂÏÂÙËı› ÂÎÙÂٷ̤ӷ Û ÂÈÚ·Ì·ÙÈο ÚfiÙ˘· (ÂÈÚ·Ì·Ùfi˙ˆ·). H ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Ô‰ÔÓÙÈÎÒÓ Î·È ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ, Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ Î·È ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡ Û ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ ÂÈÚ·Ì·Ùfi˙ˆˆÓ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÔÈÎÈÏ›· Ì¤ÛˆÓ ÌÂÙ·ÊÔÚ¿˜ ¤¯ÂÈ ‰Â›ÍÂÈ ÂÓı·ÚÚ˘ÓÙÈο ·ÔÙÂϤÛÌ·Ù· (¶›Ó. 2). ™ÙÔÓ ¿ÓıÚˆÔ, Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Û ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ ¤¯ÂÈ ÌÂÏÂÙËı› Ôχ ÂÚÈÔÚÈṲ̂ӷ. ™ÙË ‚È‚ÏÈÔÁÚ·Ê›· ˘¿Ú¯Ô˘Ó ÌfiÓÔ ·Ó·ÊÔÚ¤˜ ÂÚÈÙÒÛÂˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ·ÛıÂÓÒÓ Ô˘ ·ÓÙÈÌÂÙˆ›ÛÙËÎ·Ó Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ4, 24. ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ Yamada Î·È Û˘Ó.24 42 in human periodontal defects is limited. There are only few case reports of periodontal patients treated with mesenchymal stem cell transplantation4, 24. Specifically, Yamada et al.24 treated a mandibular second premolar intraosseous defect, which presented a 5mm-deep residual periodontal pocket (mesially and bucally) and bleeding on probing, with iliac crest bone marrow-derived mesenchymal stem cells mixed with platelet-rich plasma. At 12 months, elimination of the periodontal pocket (1mm-deep gingival sulcus) and significant gain of clinical attachment level (by 4mm messially and 3mm bucally) were achieved. McAllister4 presented two case reports, where periodontal osseous defects were treated with open flap debridement (without phase I periodontal treatment prior to surgery) and allogenic trabecular osseous graft in which the vitality of mesenchymal stem cells and osteoprogenitor cells had been preserved. An horizontal osseous defect located between maxillary central and lateral incisors, with a 9 mm-deep periodontal pocket, was treated with the allogenic graft. At 6 months, there were 4mm alveolar crest level gain and 5 mm pocket depth reduction. Moreover, a class II furcation defect, which was located lingually to a mandibular second molar and presented a 9mm-deep periodontal pocket, was treated with the allogenic graft and at 6 months the defect was eliminated (bone fill and pocket elimination). Effect of the environment on the differentiation of mesenchymal stem cells Mesenchymal stem cells have the capacity to differentiate into all cells of the tissue they derive from. However, the cell type in which they will differentiate seems to depend on the environment in which they develop. Kim et al.25 studied in immunodeficient mice the subcutaneous implantation of human periodontal mesenchymal Hellenic Stomatological Review 57: 39-71, 2013 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ¶›Ó·Î·˜ 1. EÏ¿¯ÈÛÙ· ÎÚÈÙ‹ÚÈ· Ô˘ Ú¤ÂÈ Ó· ÏËÚÔ‡Ó Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú·9 KÚÈÙ‹ÚÈ· §ÂÙÔÌÂÚ‹˜ ÂÚÈÁÚ·Ê‹ IηÓfiÙËÙ· ÚÔÛÎfiÏÏËÛ˘ Û ϷÛÙÈÎfi ¶ÚÔÛÎfiÏÏËÛË Û ϷÛÙÈÎfi fiÙ·Ó Î·ÏÏÈÂÚÁÔ‡ÓÙ·È Î¿Ùˆ ·fi Û˘ÁÎÂÎÚÈ̤Ó˜ Û˘Óı‹Î˜ Î·È ÛÂ Û˘ÁÎÂÎÚÈ̤Ó˜ ÊȿϘ. ŒÎÊÚ·ÛË Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ÂÈÊ·ÓÂÈ·ÎÒÓ ·ÓÙÈÁfiÓˆÓ TÔ˘Ï¿¯ÈÛÙÔÓ ÙÔ 95% ÙÔ˘ ÏËı˘ÛÌÔ‡ ÂÎÊÚ¿˙ÂÈ ÙÔ˘˜ ‰Â›ÎÙ˜ CD105, CD73 Î·È CD90 Î·È ÏÈÁfiÙÂÚÔ ·fi ÙÔ 2% ÙÔ˘˜ ‰Â›ÎÙ˜ CD45, CD34, CD14 ‹ CD11b, CD79a ‹ CD19 Î·È HLA Ù¿Í˘ II. IηÓfiÙËÙ· ÔÏ˘‰‡Ó·Ì˘ ‰È·ÊÔÚÔÔ›ËÛ˘ ¢È·ÊÔÚÔÔ›ËÛË Û 3 ÛÂÈÚ¤˜ ΢ÙÙ¿ÚˆÓ, ÔÛÙÂÔ‚Ï¿ÛÙ˜, ÏÈÔ·ÙÙ·Ú· Î·È ¯ÔÓ‰ÚÔ‚Ï¿ÛÙ˜ οو ·fi Û˘ÁÎÂÎÚÈ̤Ó˜ in-vitro Û˘Óı‹Î˜. ·ÓÙÈÌÂÙÒÈÛ·Ó ÂÓ‰ÔÛÙÈ΋ ‚Ï¿‚Ë ÂÁÁ‡˜ ‰Â˘Ù¤ÚÔ˘ οو ÚÔÁÔÌÊ›Ô˘, fiÔ˘ ˘‹Ú¯Â ˘ÔÏÂÈÌÌ·ÙÈÎfi˜ ÂÚÈÔ‰ÔÓÙÈÎfi˜ ı‡Ï·ÎÔ˜ ‚¿ıÔ˘˜ 5mm (ÂÁÁ‡˜ Î·È ·ÚÂȷο) Î·È ·ÈÌÔÚÚ·Á›· ÛÙËÓ ·Ó›¯Ó¢ÛË, Ì ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ ÚÔÂÚ¯fiÌÂÓ· ·fi ÙË Ï·ÁÒÓÂÈ· ·ÎÚÔÏÔÊ›· ·Ó·ÌÂÌÂÈÁ̤ӷ Ì ϿÛÌ· ˘„ËÏ‹˜ ÂÚÈÂÎÙÈÎfiÙËÙ·˜ Û ·ÈÌÔÂÙ¿ÏÈ·. MÂÙ¿ ·fi 1 ¯ÚfiÓÔ, ·Ú·ÙËÚ‹ıËΠÂÍ¿ÏÂÈ„Ë ÙÔ˘ ı˘Ï¿ÎÔ˘ (‚¿ıÔ˜ Ô˘ÏÔ‰ÔÓÙÈ΋˜ Û¯ÈÛÌ‹˜ 1mm) Î·È ÛËÌ·ÓÙÈ΋ ‚ÂÏÙ›ˆÛË ÙÔ˘ ÂȤ‰Ô˘ ÎÏÈÓÈ΋˜ ÚfiÛÊ˘Û˘ (ηٿ 4mm ÂÁÁ‡˜ Î·È 3mm ·ÚÂȷο). O McAllister4 ·ÚÔ˘Û›·Û ‰‡Ô ÂÚÈÛÙ·ÙÈο ÂÚÈÔ‰ÔÓÙÈÎÒÓ ·ÛıÂÓÒÓ, fiÔ˘ ÂÚÈÔ‰ÔÓÙÈΤ˜ ÔÛÙÈΤ˜ ‚Ï¿‚˜ ·ÓÙÈÌÂÙˆ›ÛÙËÎ·Ó Ì ÚÈ˙È΋ ·fiÍÂÛË Ì ÎÚËÌÓfi (¯ˆÚ›˜ Ó· ¤¯ÂÈ ÚÔËÁËı› Ë Ê¿ÛË ÂϤÁ¯Ô˘ Ù˘ ÊÏÂÁÌÔÓ‹˜ ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ) Î·È ·ÏÏÔÁÂÓ¤˜ ÌfiÛ¯Â˘Ì· ÛÔÁÁÒ‰Ô˘˜ ÔÛÙÔ‡ ÛÙÔ ÔÔ›Ô Â›¯Â ‰È·ÙËÚËı› Ë ˙ˆÙÈÎfiÙËÙ· ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Î·È ÙˆÓ ÔÛÙÂÔÚÔÁÔÓÈÎÒÓ Î˘ÙÙ¿ÚˆÓ. ™Â ÔÚÈ˙fiÓÙÈ· ÔÛÙÈ΋ ‚Ï¿‚Ë ÌÂٷ͇ ¿Óˆ ÎÂÓÙÚÈÎÔ‡ Î·È Ï¿ÁÈÔ˘ ÙÔ̤· Ì ‚¿ıÔ˜ ı˘Ï¿ÎÔ˘ 9mm, 6 Ì‹Ó˜ ÌÂÙ¿ ·fi ÙÔ ÔÛÙÈÎfi ÌfiÛ¯Â˘Ì· ·Ó·Ê¤ÚıËΠ‚ÂÏÙ›ˆÛË ÙÔ˘ ÂȤ‰Ô˘ ÙÔ˘ Ê·ÙÓÈ·ÎÔ‡ ÔÛÙÔ‡ ηٿ 4mm Î·È Ì›ˆÛË ÙÔ˘ ‚¿ıÔ˘˜ ı˘Ï¿ÎÔ˘ Û 4mm. AÓÙ›ÛÙÔȯ·, Û ‚Ï¿‚Ë Ù˘ ÂÚÈÔ¯‹˜ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÚÈ˙ÒÓ Î·ÙËÁÔÚ›·˜ II ÁψÛÛÈο ‰Â˘Ù¤ÚÔ˘ οو ÁÔÌÊ›Ô˘ Ì ‚¿ıÔ˜ ı˘Ï¿ÎÔ˘ 9mm, 6 Ì‹Ó˜ ÌÂÙ¿ ·fi ÙÔ ÔÛÙÈÎfi ÌfiÛ¯Â˘Ì· ·Ó·Ê¤ÚıËΠÂÍ¿ÏÂÈ„Ë Ù˘ ‚Ï¿‚˘ (ÔÛÙÈ΋ Ï‹ÚˆÛË Î·È ÂÍ¿ÏÂÈ„Ë ÙÔ˘ ı˘Ï¿ÎÔ˘). E›‰Ú·ÛË ÙÔ˘ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ T· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· Ó· ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û fiÏ· Ù· ·ÙÙ·Ú· ÙÔ˘ ÈÛÙÔ‡ ·fi ÙÔÓ ÔÔ›Ô ÚÔ¤Ú¯ÔÓÙ·È. øÛÙfiÛÔ ÙÔ Â›‰Ô˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÛÙÔ ÔÔ›Ô ı· ‰È·ÊÔÚÔÔÈËıÔ‡Ó Ê·›ÓÂÙ·È Ó· ÂÍ·ÚÙ¿Ù·È ·fi ÙÔ ÂÚÈ‚¿ÏÏÔÓ ÛÙÔ ÔÔ›Ô ·Ó·Ù‡ÛÛÔÓÙ·È. OÈ Kim Î·È Û˘Ó.25 ÌÂϤÙËÛ·Ó Û ·ÓÔÛÔ·Ó·Ú΋ ÔÓÙ›ÎÈ· Hellenic Stomatological Review 57: 39-71, 2013 stem cells mixed with hydroxyapatite and b-tricalcium phosphate granules. Initially, on the third day and at the end of the first week, proliferation and migration of mesenchymal stem cells among the graft granules was noted. Moreover, there was a shapeless collagen mass. The morphology of the cell nuclei differed depending on the area. There were sparsely ordered cementoblast-like cells with round nuclei around the granules, whereas dispersed fibroblast-like cells with atractoid nuclei were found within the shapeless collagen mass. At the end of the second week, the shapeless collagen mass had been transformed into well-organized collagen fibers, located among the granules and in contact with them. Cells with round nuclei were densely ordered in a layer around the granules. Eosinophilic non-mineralized cementoid-like tissue was found among the round nuclei cells and the granules. There were collagen fibers, similar to Sharpey’s fibers, entering the eosinophilic tissue. At the end of the fourth week, the cementoid-like tissue surrounding the granules seemed to get mineralized. Well-organized fibers, similar to Sharpey’s fibers, ended into this cementum-like tissue. Furthermore, there were concave areas on the granule surface with increased density of cementoblast-like cells, cementum-like tissue and fibers, similar to Sharpey’s fibers. Park et al.15 studied the subcutaneous implantation of human periodontal mesenchymal stem cells mixed with hydroxyapatite and b-tricalcium phosphate bone graft granules in immunodeficient mice. After 8 weeks, there were cellular cementum containing cementocytes (cementoblasts which had been entrapped into the cementum during the process of its output) and Sharpey’s fibers entering into the cementum. In this study, periodontal tissue-derived mesenchymal stem cells produced periodontal connective like-tissue and cementum-like tissue. The cells which were in contact with the graft granules differe43 44 M¤ÛÔ PRP, ÊıÔÚÈÔ¸‰ÚÔ͢··Ù›Ù˘ PRP XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ ÔÛÙÈΤ˜ ‚Ï¿‚˜ ‰È·Ì¤ÙÚÔ˘ 3.5mm Î·È ‚¿ıÔ˘˜ 8mm OÛÙÈΤ˜ ‚Ï¿‚˜ ™Î‡ÏÔÈ XÔÈÚ›‰È· ™Î‡ÏÔÈ ZÒ· MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· K‡ÙÙ·Ú· ¶ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ ÛÙÔÓ ·ÚÂÈ·Îfi ÊÏÔÈfi Ù˘ οو ÁÓ¿ıÔ˘ KÔÏÏ·ÁÔÓÔ‡¯o˜ ÛfiÁÁÔ˜ AÓÔÛÔ·Ó·Ú΋ ÔÓÙ›ÎÈ· EÙÂÚÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÔ‰ÔÓÙ›Ô˘ MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ô‰ÔÓÙÈÎÒÓ Î·È ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ ¶Ï¿ÛÌ· ÏÔ‡ÛÈÔ Û ·ÈÌÔÂÙ¿ÏÈ· (PRP) XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ ‚Ï¿‚˜ Ù˘ ÂÚÈÔ¯‹˜ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÚÈ˙ÒÓ ÚÔÁÔÌÊ›ˆÓ ηÙËÁÔÚ›·˜ II ‡„Ô˘˜ 5mm Î·È ‚¿ıÔ˘˜ 2mm MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· BÏ¿‚Ë - 2,4 Î·È 8 ‚‰ÔÌ¿‰Â˜ 3 Ì‹Ó˜ 8 ‚‰ÔÌ¿‰Â˜ ¢È¿ÚÎÂÈ· ¢ËÌÈÔ˘ÚÁ›· ÈÛÙÔ‡ ÚÔÛÔÌÔÈ¿˙ÔÓÙ· Ì ÂÚÈÚÚ›˙ÈÔ, ÎÔÏÏ·ÁfiÓˆÓ ÈÓÒÓ Î·È ÔÛÙÔ‡ ·ÏÏ¿ ÌË ÏÂÈÙÔ˘ÚÁÈ΋ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ. ™ÙȘ 2 Î·È 4 ‚‰ÔÌ¿‰Â˜ ‰ËÌÈÔ˘ÚÁ›· ηϿ Û¯ËÌ·ÙÈṲ̂ÓÔ˘ ÒÚÈÌÔ˘ ÔÛÙÔ‡ Î·È ·ÁÁÂÈ·ÎÔ‡ ÈÛÙÔ‡ Û ۇÁÎÚÈÛË Ì ·Ô˘Û›· ıÂڷ›·˜, ÌfiÓÔ ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ Î·È Û˘Ó‰˘·ÛÌfi ·˘ÙÔÁÂÓÔ‡˜ ÛÔÁÁÒ‰Ô˘˜ ÔÛÙÔ‡ Î·È Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ. ¢ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡: ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË Û ۇÁÎÚÈÛË Ì ·Ô˘Û›· ıÂڷ›·˜ Î·È ÌfiÓÔ ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ ÛÙȘ 8 ‚‰ÔÌ¿‰Â˜, ·ÚfiÌÔÈ· ÌÂ Û˘Ó‰˘·ÛÌfi ·˘ÙÔÁÂÓÔ‡˜ ÛÔÁÁÒ‰Ô˘˜ ÔÛÙÔ‡ Î·È Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ. ¢ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡: ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË Û ۇÁÎÚÈÛË Ì ÊıÔÚÈÔ¸‰ÚÔ͢··Ù›ÙË ÛÂ Û˘Ó‰˘·ÛÌfi ‹ ÌË Ì PRP, ·ÚfiÌÔÈ· Ì ·˘ÙÔÁÂÓ¤˜ ÔÛÙÔ‡Ó. ™Ù·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË Â·Ê‹ ÌÂٷ͇ ÊıÔÚÈÔ¸‰ÚÔ͢··Ù›ÙË Î·È ÓÂÔ‰ËÌÈÔ˘ÚÁËı¤ÓÙÔ˜ ÔÛÙÔ‡ Û ۯ¤ÛË Ì ÊıÔÚÈÔ¸‰ÚÔ͢··Ù›ÙË ÛÂ Û˘Ó‰˘·ÛÌfi ‹ ÌË Ì PRP. ¢ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡: ·ÚfiÌÔÈ· ÁÈ· fiϘ ÙȘ ÔÌ¿‰Â˜ ¢ËÌÈÔ˘ÚÁ›· ÔÛÙ½Ó˘: ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË Û ۇÁÎÚÈÛË Ì ÙËÓ Ê¿ÛË ÂϤÁ¯Ô˘ ÊÏÂÁÌÔÓ‹˜ Î·È ÌfiÓÔ ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜, ·ÚfiÌÔÈ· Ì ·˘ÙÔÁÂÓ¤˜ Û˘Ì·Á¤˜ ÔÛÙÔ‡Ó ÛÂ Û˘Ó‰˘·ÛÌfi ‹ ÌË Ì ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ AÔÙÂϤÛÌ·Ù· 13 12 11 10 MÂϤÙË ¶›Ó·Î·˜ 2. MÂϤÙ˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ Î·È ÂÚÈÂÌÊ˘ÙÂ˘Ì·ÙÈÎÒÓ ÈÛÙÒÓ Û ÂÈÚ·Ì·Ùfi˙ˆ·. μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Hellenic Stomatological Review 57: 39-71, 2013 Hellenic Stomatological Review 57: 39-71, 2013 - - - ¶ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ ÂÂÎÙÂÈÓfiÌÂÓ˜ ̤¯ÚÈ ÙÔ ·ÎÚÔÚÚ›˙ÈÔ XÂÈÚÔ˘ÚÁÈο ‰ËÌÈÔ˘ÚÁË̤Ó˜ ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ KÚ›ÛÈÌÔ˘ ÌÂÁ¤ıÔ˘˜ ÔÛÙÈΤ˜ ‚Ï¿‚˜ ÛÙËÓ Î¿Ùˆ ÁÓ¿ıÔ XÔÈÚ›‰È· XÔÈÚ›‰È· ™Î‡ÏÔÈ beagle New Zealand Ï·ÁÔ› KfiÏÏ· ÈÓÒ‰Ô˘˜ AÙÂÏÔÎÔÏÏ·ÁfiÓÔ XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ ‚Ï¿‚˜ ÛÙÔ Ê·ÙÓÈ·Îfi ÔÛÙfi Ù˘ ¿Óˆ ÁÓ¿ıÔ˘ XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ ‚Ï¿‚˜ Ù˘ ÂÚÈÔ¯‹˜ Û˘Ì‚ÔÏ‹˜ ™Î‡ÏÔÈ beagle SpragueDawley Â›Ì˘Â˜ MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ AÓ·Û˘Ó‰˘·Ṳ̂ÓË ·ÓıÚÒÈÓË ÌÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡-2, Ó·ÓÔ¸‰ÚÔ͢··Ù›Ù˘, ÎÔÏÏ·ÁfiÓÔ, ÔÏ˘-LÏ·ÎÙ›‰ÈÔ KÚ›ÛÈÌÔ˘ ÌÂÁ¤ıÔ˘˜ ÔÛÙÈΤ˜ ‚Ï¿‚˜ ÛÙÔ Ê·ÙÓÈ·Îfi ÔÛÙÔ‡Ó A˘ÙÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ A˘ÙÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÓÂÔÁÈÏÒÓ ‰ÔÓÙÈÒÓ A˘ÙÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÂÚÈÚÚÈ˙›Ô˘ A˘ÙÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÂÚÈÚÚÈ˙›Ô˘ ‹ ÔÏÊÔ‡ ‹ Ô‰ÔÓÙÔı˘Ï·Î›Ô˘ A˘ÙÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÔÏÊÔ‡ 4 ‚‰ÔÌ¿‰Â˜ 6 ‚‰ÔÌ¿‰Â˜ 6 Ì‹Ó˜ - - 12 ‚‰ÔÌ¿‰Â˜ ™¯Â‰fiÓ Ï‹Ú˘ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ. EÓÙÔÈÛÌfi˜ ÛËÌ·ÛÌ¤ÓˆÓ ÔÛÙÂÔ‚Ï·ÛÙÒÓ, ÔÛÙÂÔ΢ÙÙ¿ÚˆÓ, ÔÛÙ½ÓÔ‚Ï·ÛÙÒÓ Î·È ÈÓÔ‚Ï·ÛÙÒÓ ÚÔÂÚ¯fiÌÂÓˆÓ ·fi Ù· ÛËÌ·Ṳ̂ӷ ™Ù·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡ Û ۇÁÎÚÈÛË Ì ·Ô˘Û›· ıÂڷ›·˜ Î·È ÌfiÓÔ ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜. AÓ¿Ï·ÛË ÙÔ˘ ÔÛÙÔ‡. AÓ¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ. T· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÚÚÈ˙›Ô˘ ·ÚÔ˘Û›·Û·Ó ÙË ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡, ÂÚÈÚÚÈ˙›Ô˘ Î·È ÔÛÙ½Ó˘, Ó¢ÚÈÎÔ‡ Î·È ·ÁÁÂÈ·ÎÔ‡ ÈÛÙÔ‡. ¶Úˆ˚ÌfiÙÂÚË ÂÓ·Û‚ÂÛÙ›ˆÛË Î·È ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡ Û ۇÁÎÚÈÛË Ì ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜, Û˘Ó‰˘·ÛÌfi ÙÔ˘ ̤ÛÔ˘ ÌÂÙ·ÊÔÚ¿˜ Ì ·Ó·Û˘Ó‰˘·Ṳ̂ÓË ·ÓıÚÒÈÓË ÌÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡-2, Û˘Ó‰˘·ÛÌfi ÙÔ˘ ̤ÛÔ˘ ÌÂÙ·ÊÔÚ¿˜ Ì ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú·, ·˘ÙÔÁÂÓ¤˜ ÔÛÙÔ‡Ó. 19 18 17 16 15 14 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review 45 46 PRP E›Ì˘Â˜ Wistar Y‰ÚÔ͢··Ù›Ù˘/‚ʈÛÊÔÚÈÎfi ·Û‚¤ÛÙÈÔ PRP XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ ·Ú·ÏÏËÏfiÁÚ·Ì̘ ÂÊÈÈÔÂȉ›˜ ÂÚÈÂÌÊ˘ÙÂ˘Ì·ÙÈΤ˜ ‚Ï¿‚˜ XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ ÔÛÙÈΤ˜ ‚Ï¿‚˜ Y‚ÚȉÈÎÔ› Û·ÏÔÈ ™Î‡ÏÔÈ beagle MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ‰È·ÊÔÚÂÙÈÎÒÓ ÈÛÙÒÓ ¶ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡ A˘ÙÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· A˘ÙÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ ‹ ÂÚÈÚÚÈ˙›Ô˘ AÏÏÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡ A˘ÙÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ KÔÏÏ·ÁfiÓÔ ¶ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ 5x5mm ÂÎÙÂÈÓfiÌÂÓ˜ ·fi ÙËÓ ·‰·Ì·ÓÙÈÓÔÔÛÙ½ÓÈ΋ ¤ÓˆÛË ™Î‡ÏÔÈ beagle A˘ÙÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ AÙÂÏÔÎÔÏÏ·ÁfiÓÔ ÛÂ Û˘ÁΤÓÙÚˆÛË 2x106, 5x106, 1x107, Î·È 2x107 ·ÙÙ·Ú·/ml XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ ‚Ï¿‚˜ Ù˘ ÂÚÈÔ¯‹˜ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÚÈ˙ÒÓ Î·ÙËÁÔÚ›·˜ III ™Î‡ÏÔÈ beagle ÔÛÙÒÓ ÙˆÓ ÚÈ˙ÒÓ Î·ÙËÁÔÚ›·˜ III 2,4 Î·È 8 ‚‰ÔÌ¿‰Â˜ 8 Î·È 16 ‚‰ÔÌ¿‰Â˜ 2, 4, 8 ‚‰ÔÌ¿‰Â˜ 8 ‚‰ÔÌ¿‰Â˜ 1 Ì‹Ó·˜ ™ÙȘ 4 Î·È 8 ‚‰ÔÌ¿‰Â˜ ‰ËÌÈÔ˘ÚÁ›· ·ÁÁÂÈ·ÎÔ‡ ÈÛÙÔ‡ Î·È ÒÚÈÌÔ˘ ÔÛÙÔ‡, ıÂÙÈÎÔ‡ ÁÈ· ÔÛÙÂÔηÏÛ›ÓË ÛÙȘ 8 ‚‰ÔÌ¿‰Â˜. ™Ù·ÙÈÛÙÈο ¢ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡: ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË Û ۇÁÎÚÈÛË Ì ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ ÌfiÓÔ, ÌÂÁ·Ï‡ÙÂÚË ÁÈ· Ù· ·‰È·ÊÔÚÔÔ›ËÙ· ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ ÛÙȘ 8 ‚‰ÔÌ¿‰Â˜. ™ÙȘ 16 ‚‰ÔÌ¿‰Â˜ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡ ÌfiÓÔ ÁÈ· Ù· ·‰È·ÊÔÚÔÔ›ËÙ· ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ. T· ÛËÌ·Ṳ̂ӷ Ì ÊıÔÚÈÛÌfi ÌÂÙ·ÌÔÛ¯Â˘Ì¤Ó· ·ÙÙ·Ú· ·ÓȯÓ‡ıËÎ·Ó Û ·ʋ Ì ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ Î·È ÌÂÚÈÎÒ˜ Ì ÙÔ Û˘Ó‰ÂÙÈÎfi ÈÛÙfi Î·È ÙÔ ÔÛÙÂÔÂȉ¤˜. ™ÙȘ 2 Î·È 4 ‚‰ÔÌ¿‰Â˜ ÌÈÎÚ‹ ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡. ™ÙȘ 8 ‚‰ÔÌ¿‰Â˜ ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡ Î·È ÈÛÙÔ‡ ÚÔÛÔÌÔÈ¿˙ÔÓÙÔ˜ Ì ÂÚÈÚÚ›˙ÈÔ. ™Ù·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡, ÔÛÙ½Ó˘ Î·È ÂÚÈÚÚÈ˙›Ô˘ Û ۇÁÎÚÈÛË Ì ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ ÌfiÓÔ. H ÎÚ˘Ô‰È·Ù‹ÚËÛË ÙˆÓ ·‰È·ÊÔÚÔÔ›ËÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ‰ÂÓ Â›¯Â ÂÈÙÒÛÂȘ ÛÙÔ ıÂڷ¢ÙÈÎfi ·ÔÙ¤ÏÂÛÌ·. MÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Û ۇÁÎÚÈÛË Ì ·ÙÂÏÔÎÔÏÏ·ÁfiÓÔ. TÔ ÔÛÔÛÙfi ÙÔ˘ Ì‹ÎÔ˘˜ Ù˘ ÔÛÙ½Ó˘ ÁÈ· ÙË Û˘ÁΤÓÙÚˆÛË ·ÙÂÏÔÎÔÏÏ·ÁfiÓÔ˘ 5x106 Î·È 2x107 ·ÙÙ·Ú·/ml Î·È ÙÔ ÔÛÔÛÙfi ÙÔ˘ ÓÂÔ‰ËÌÈÔ˘ÚÁËı¤ÓÙÔ˜ ÔÛÙÔ‡ ÁÈ· ÙË Û˘ÁΤÓÙÚˆÛË ·ÙÂÏÔÎÔÏÏ·ÁfiÓÔ˘ 2x107 ·ÙÙ·Ú·/ml ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚ·. Ì ڿÛÈÓË ÊıÔÚ›˙Ô˘Û· ÚˆÙ½ÓË ÌÂÙ·ÌÔÛ¯Â˘Ì¤Ó· ·ÙÙ·Ú· ÛÙÔÓ ÓÂÔ‰ËÌÈÔ˘ÚÁËı¤ÓÙ· Û˘Ó‰ÂÙÈÎfi ÈÛÙfi. 23 5 22 21 20 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Hellenic Stomatological Review 57: 39-71, 2013 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ ‹ Ô‰ÔÓÙÈÎÔ‡ ÔÏÊÔ‡ ‹ ·ÏÏÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÓÂÔÁÈÏÒÓ ‰ÔÓÙÈÒÓ ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡ ÛÙȘ 8 ‚‰ÔÌ¿‰Â˜ Û ۇÁÎÚÈÛË Ì ·Ô˘Û›· ıÂڷ›·˜ Î·È ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ ÌfiÓÔ. Literature Review ntiated into cementoblast-like cells and produced cementum-like tissue. It has been reported that the hydroxyapatite and b-calcium phosphate granules (due to their morphology and release of calcium and phosphate ions) become apatite aggregation nodules which enhance the differentiation of mesenchymal stem cells into cells producing mineralized tissues15. During the morphogenesis of the dental tissues, prior to cementum formation, dental follicle cells penetrate the disintegrated Hertwig’s epithelial root sheath and come in contact with non-mineralized root dentin matrix. Wen et al.26 explored the impact of the contact between dental follicle cells and dentin matrix on cementoblast differentiation and cementum formation. They studied the differentiation of adipose tissue-derived mesenchymal stem cells cultured in the medium of dental follicle cells, where non-collagenous dentin proteins were added. The spindle-shaped cells were transformed into cementoblast-like, flat, cuboidal or polygonal cells. Cell proliferation was suppressed whereas cell differentiation was enhanced. Cells exhibited high alkaline-phosphatase (ALP) activity and calcified nodule formation. Moreover, mineralization markers mainly expressed in the dental hard tissues, by cementoblasts, odontoblasts or ameloblasts, were detected at mRNA and protein level, such as bone sialoprotein (BSP), osteonectin (ON), osteocalcin (OCN), osteopontin (OPN) and type I collagen. However, cementoblast-specific cementum attachment protein (CAP) was detected whereas odontoblast-specific dentin sialophosphoprotein gene, which encodes two major non-collagenous dentine matrix proteins, dentin sialoprotein and phosphoprotein, was not detected. Therefore, Wen et al.’s study26 demonstrated that mesenchymal stem cells differentiated into cells with cementoblast characteristics. Risk of carcinogenesis by mesenchymal stem cells The ability of mesenchymal stem cells to differentiate into various cell lineages entails the risk of carcinogenesis. The type of the transplanted cells and the environment of the recipient area affect the chance of developing cancer27. Carcinogenesis after mesenchymal stem cell transplantation for periodontal tissue regeneration has not been reported. Culturing mesenchymal stem cells in a medium promoting differentiation into a specific cell type, prior to transplantation, has been reported to reduce the carcinogenesis risk27. Immunogenic and immunomodulatory properties of the allogenic mesenchymal stem cells The mesenchymal stem cells might be of autologous or allogeneic origin. The autologous mesenchymal stem cells do not induce immune reaction. However, their ability to produce an adequate number of cells is doubtful due to differences in cell growth and differentiation among individuals. Allogenic mesenchymal stem cells have specific regenerative potential. However, they entail Hellenic Stomatological Review 57: 39-71, 2013 47 48 PRP, fluorohydroxyapatite PRP Surgically induced osseous defects of 3.5mm diameter and 8mm depth Osseous defects Dogs Minipigs Dogs Animal model Mesenchymal stem cells Mesenchymal stem cells Mesenchymal stem cells Transplanted cells Mandibular buccal cortical periodontal defects Collagensponge Immunodeficient mice Heterologous periodontalderived mesenchymal stem cells Dental and periodontal tissue-derived mesenchymal stem cells Platelet-rich plasma(PRP) Vehicle Surgically induced premolar class II furcation defects of 5mm height and 2mm depth Mesenchymal stem cells Defect Not reported 2, 4 and 8 weeks 3 months 8 weeks Study duration Creation of periodontal ligament-like tissue, collagen fibers and bone, but no regeneration of functional periodontal tissues. At 2 and 4 weeks well-formed mature bone and vascular tissue creation as compared to absence of treatment, vehicle only and combination of autologous trabecular bone and bone marrow. Bone creation: statistically significantly higher at 8 weeks as compared to absence of treatment and vehicle only, similar to combination of autologous trabecular bone and bone marrow. Bone creation: statistically significanly higher as compared to fluorohydroxyapatite and combination of fluorohydroxyapatite with PRP, similar to autologous bone. Statistically significantly higher contact between fluorohydroxyapatite and newly-created bone as compared to fluorohydroxyapatite and combination of fluorohydroxyapatite with PRP. Bone creation: similar for all groups. Cementum creation: statistically significantly higher as compared to phase I periodontal treatment and vehicle only, similar to autologous cortical bone and combination of autologous cortical bone with PRP. Results Table 2: Mesenchymal stem cell transplantation studies for periodontal and peri-implant tissue regeneration in animal models. 13 12 11 10 Study μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Hellenic Stomatological Review 57: 39-71, 2013 Hellenic Stomatological Review 57: 39-71, 2013 Minipigs Autologous deciduous teeth-derived mesenchymal stem cells Periodontal ligamentderived mesenchymal stem cells Atelocollagen Beagle dogs Autologous bone marrowderived Not reported Critical size mandibular osseous defects Minipigs Autologous periodontal ligament, pulp or dental follicle-derived mesenchymal stem cells Surgically induced class III furcation defects Not reported Surgically induced periodontal defects Beagle dogs Autologous pulp-derived mesenchymal stem cells Bone marrowderived mesenchymal stem cells Not reported Periodontal defects extending to the apex New Zealand rabbits Bone marrow-derived mesenchymal stem cells Maxillary alveolar Fibrin Sprabone traumatic glue guedefects Dawley rats Human recombinant bone morphogenetic protein, nanohydroxyapatite, collagen, poly-Llactide Critical size alveolar osseous defects 4 weeks 6 weeks 6 months - - 12 weeks Almost complete periodontal tissue regeneration. Detection of labeled osteoblasts, osteocytes, cementoblasts and fibroblasts Statistically significantly higher bone creation as compared to absence of treatment and application of vehicle only. Bone regeneration Periodontal tissue regeneration Periodontal ligament-derived mesenchymal stem cells presented the highest bone, periodontal ligament, cementum, neural and vascular tissue creation. More rapid mineralization and higher bone creation as compared to vehicle only, combination of vehicle with BMP-2, combination of vehicle with mesenchymal stem cells, autologous bone. 19 18 17 16 15 14 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review 49 50 Collagen Periodontal defects (5x5mm) extending from cementoenamel junction andapically Beagle dogs Beagle dogs PRP Wistar rats Surgically induced osseous defects Surgically induced rectangular, saddlelike peri-implant defects PRP Hybrid dogs Hydroxyapati- Beagle te/‚-tricalcium- dogs phosphate Diverse tissue-derived mesenchymal stem cells Periodontal defects Adipose tissue-derived mesenchymal stem cells Atelocollagen in concentrations 2x106, 5x106, 1x107,and 2x107 cells/ml Surgically induced class III furcation defects Autologous bone marrowor dental pulpderived or allogenic deciduous teeth-derived mesenchymal stem cells Autologous bone marrowor periodontal ligamentderived mesenchymal stem cells Allogenic adipose tissuederived mesenchymal stem cells Autologous bone marrowderived mesenchymal stem cells Autologous bone marrowderived mesenchymal stem cells mesenchymal stem cells 2,4 and 8 weeks 8 and 16 weeks 2,4 and 8 weeks 8 weeks 1 month At 4 and 8 weeks vascular tissue and mature bone creation, at 8 weeks osteocalcin-positive tissue. Statistically significantly higher bone creation at 8 weeks as compared to absence of treatment and vehicle only. Bone creation: statistically significantly higher as compared to vehicle only, higher for bone marrow-derived mesenchymal stem cells at 8 weeks. At 16 weeks statistically significantly higher bone creation only for bone marrowderived mesenchymal stem cells. Fluorescentlabeled transplanted cells were detected in contact to the vehicle and partially to connective tissue and osteoid At 2 and 4 weeks low bone creation. At 8 weeks bone and periodontal ligament-like tissue creation. Statistically significantly higher bone, cementum and periodontal ligament creation as compared to vehicle only. Mesenchymal stem cell cryopreservation had no effect on the therapeutic result. Higher periodontal tissue creation as compared to atelocollagen. Statistically significantly higher % of newly-created cementum length for atelocollagen concentration of 5x106 and 2x107 cells/ml and statisticallysignificanly higher % of newly-created bone for atelocollagen concentration of 2x107 cells/ml were. deriving from GFP-labeled cells transplanted in the newly-created connective tissue. 23 5 22 21 20 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Hellenic Stomatological Review 57: 39-71, 2013 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ÙËÓ ˘Ô‰fiÚÈ· ÂÌʇÙ¢ÛË ·ÓıÚÒÈÓˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÙÔ˘ ÂÚÈÔ‰ÔÓÙ›Ô˘ ·Ó·ÌÂÌÂÈÁÌ¤ÓˆÓ Ì ÎfiÎÎÔ˘˜ ÔÛÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜, ·ÔÙÂÏÔ‡ÌÂÓÔ˘ ·fi ˘‰ÚÔ͢··Ù›ÙË Î·È ‚-ʈÛÊÔÚÈÎfi ·Û‚¤ÛÙÈÔ. AÚ¯Èο, ÙËÓ ÙÚ›ÙË Ë̤ڷ Î·È ÛÙÔ Ù¤ÏÔ˜ Ù˘ ÚÒÙ˘ ‚‰ÔÌ¿‰·˜, ·Ú·ÙËÚ‹ıËΠÔÏÏ·Ï·ÛÈ·ÛÌfi˜ Î·È ÌÂÙ·Ó¿ÛÙ¢ÛË ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÌÂٷ͇ ÙˆÓ ÎfiÎÎˆÓ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. E›Û˘, ·Ú·ÙËÚ‹ıËΠ‰ËÌÈÔ˘ÚÁ›· ¿ÌÔÚÊ˘ Ì¿˙·˜ ÎÔÏÏ·ÁfiÓÔ˘. H ÌÔÚÊÔÏÔÁ›· ÙˆÓ ˘Ú‹ÓˆÓ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ‰È¤ÊÂÚ ÌÂٷ͇ ÙˆÓ ‰È·ÊfiÚˆÓ ÂÚÈÔ¯ÒÓ. °‡Úˆ ·fi ÙÔ˘˜ ÎfiÎÎÔ˘˜ ·Ú·ÙËÚ‹ıËÎ·Ó ·Ú·È¿ ‰È·ÙÂÙ·Á̤ӷ ·ÙÙ·Ú· Ì ΢ÎÏÔÙÂÚ‹ ˘Ú‹Ó· ÚÔÛÔÌÔÈ¿˙ÔÓÙ· Ì ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ ÂÓÒ Ì¤Û· ÛÙËÓ ¿ÌÔÚÊË Ì¿˙· ÎÔÏÏ·ÁfiÓÔ˘ ‚Ú¤ıËÎ·Ó ‰È¿Û·ÚÙ· ·ÙÙ·Ú· Ì ·ÙÚ·ÎÙÔÂȉ‹ ˘Ú‹Ó· ÚÔÛÔÌÔÈ¿˙ÔÓÙ· Ì ÈÓÔ‚Ï¿ÛÙ˜. ™ÙÔ Ù¤ÏÔ˜ Ù˘ ‰Â‡ÙÂÚ˘ ‚‰ÔÌ¿‰·˜, Ë ¿ÌÔÚÊË Ì¿˙· ÎÔÏÏ·ÁfiÓÔ˘ ›¯Â ·ÓÙÈηٷÛÙ·ı› ·fi ηϿ ÔÚÁ·ÓˆÌ¤Ó˜ ›Ó˜ ÎÔÏÏ·ÁfiÓÔ˘ ·Ó¿ÌÂÛ· ÛÙÔ˘˜ ÎfiÎÎÔ˘˜ Î·È Û ·ʋ Ì ·˘ÙÔ‡˜. T· ·ÙÙ·Ú· Ô˘ ›¯·Ó ΢ÎÏÔÙÂÚ‹ ˘Ú‹Ó· ‹Ù·Ó ˘ÎÓ¿ ‰È·ÙÂÙ·Á̤ӷ Û ÛÙÈ‚¿‰· Á‡Úˆ ·fi ÙÔ˘˜ ÎfiÎÎÔ˘˜. HˆÛÈÓfiÊÈÏÔ˜ ÌË ÂÓ·Û‚ÂÛÙȈ̤ÓÔ˜ ÈÛÙfi˜ ÚÔÛÔÌÔÈ¿˙ˆÓ Ì ÔÛÙÂ˚ÓÔÂȉ¤˜ ·Ú·ÙËÚ‹ıËΠÌÂٷ͇ ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ì ΢ÎÏÔÙÂÚ‹ ˘Ú‹Ó· Î·È ÙˆÓ ÎfiÎΈÓ. M¤Û· ÛÙÔÓ ËˆÛÈÓfiÊÈÏÔ ÈÛÙfi ÂÈÛ¤Ú¯ÔÓÙ·Ó ›Ó˜ ÎÔÏÏ·ÁfiÓÔ˘, ·ÚfiÌÔȘ Ì ›Ó˜ ÙÔ˘ Sharpey. ™ÙÔ Ù¤ÏÔ˜ Ù˘ ٤ٷÚÙ˘ ‚‰ÔÌ¿‰·˜, Ô ÚÔÛÔÌÔÈ¿˙ˆÓ Ì ÔÛÙÂ˚ÓÔÂȉ¤˜ ÈÛÙfi˜ Ô˘ ÂÚȤ‚·Ï ٷ ÎÔÎΛ· Ê¿ÓËΠӷ ÂÓ·Û‚ÂÙÈÒÓÂÙ·È. M¤Û· Û ·˘ÙfiÓ ÙÔÓ ÚÔÛÔÌÔÈ¿˙ÔÓÙ· Ì ÔÛÙ½ÓË ÂÓ·Û‚ÂÛÙȈ̤ÓÔ ÈÛÙfi η٤ÏËÁ·Ó ηϿ ÔÚÁ·ÓˆÌ¤Ó˜ ›Ó˜ ·ÚfiÌÔȘ Ì ›Ó˜ ÙÔ˘ Sharpey. E›Û˘ ·Ú·ÙËÚ‹ıËÎ·Ó ÎԛϘ ÂÚÈÔ¯¤˜ Ù˘ ÂÈÊ¿ÓÂÈ·˜ ÙˆÓ ÎfiÎÎˆÓ Ì ·˘ÍË̤ÓË ˘ÎÓfiÙËÙ· ΢ÙÙ¿ÚˆÓ ÚÔÛÔÌÔÈ·˙fiÓÙˆÓ Ì ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜, ÈÛÙfi˜ ÚÔÛÔÌÔÈ¿˙ˆÓ Ì ÔÛÙ½ÓË Î·È ›Ó˜ ·ÚfiÌÔȘ Ì ›Ó˜ ÙÔ˘ Sharpey. OÈ Park Î·È Û˘Ó.15 ÌÂϤÙËÛ·Ó Â›Û˘ ÙËÓ ˘Ô‰fiÚÈ· ÂÌʇÙ¢ÛË ·ÓıÚÒÈÓˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÙÔ˘ ÂÚÈÔ‰ÔÓÙ›Ô˘ ·Ó·ÌÂÌÂÈÁÌ¤ÓˆÓ Ì ÎfiÎÎÔ˘˜ ÔÛÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ˘‰ÚÔ͢··Ù›ÙË Î·È ‚-ʈÛÊÔÚÈÎÔ‡ ·Û‚ÂÛÙ›Ô˘ Û ·ÓÔÛÔ·Ó·Ú΋ ÔÓÙ›ÎÈ·. MÂÙ¿ ·fi 8 ‚‰ÔÌ¿‰Â˜ ·Ú·Ù‹ÚËÛ·Ó ‰ËÌÈÔ˘ÚÁ›· ΢ÙÙ·ÚÔÊfiÚÔ˘ ÔÛÙ½Ó˘ Ô˘ ÂÚÈ›¯Â ÔÛÙÂ˚ÓÔ·ÙÙ·Ú·, ‰ËÏ·‰‹ ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ Ô˘ ›¯·Ó ÂÁÎψ‚ÈÛÙ› Û ·˘Ù‹Ó ηٿ ÙË ‰È·‰Èηۛ· ÂÓ·fiıÂÛ‹˜ Ù˘, ̤۷ ÛÙËÓ ÔÔ›· ÂÈÛ¤Ú¯ÔÓÙ·Ó ›Ó˜ ÙÔ˘ Sharpey. ™ÙË ÌÂϤÙË ·˘Ù‹, Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÔ‰ÔÓÙ›Ô˘ ·Ú‹Á·Á·Ó ÈÛÙfi ÚÔÛÔÌÔÈ¿˙ÔÓÙ· ÌÂ Û˘Ó‰ÂÙÈÎfi ÈÛÙfi ÙÔ˘ ÂÚÈÔ‰ÔÓÙ›Ô˘ Î·È ÔÛÙ½ÓË. T· ·ÙÙ·Ú· Ô˘ ‚Ú›ÛÎÔÓÙ·Ó Û ·ʋ Ì ÙÔ˘˜ ÎfiÎÎÔ˘˜ ÙÔ˘ ÔÛÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ‰È·ÊÔÚÔÔÈ‹ıËÎ·Ó Û ·ÙÙ·Ú· ÚÔÛÔÌÔÈ¿˙ÔÓÙ· Ì ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ Î·È ·Ú‹Á·Á·Ó ÈÛÙfi ÚÔÛÔÌÔÈ¿˙ÔÓÙ· Ì ÔÛÙ½ÓË. Œ¯ÂÈ ·Ó·ÊÂÚı› ˆ˜ Ù· ÎÔÎΛ· ˘‰ÚÔ͢··Ù›ÙË Î·È ‚-ʈÛÊÔÚÈÎÔ‡ ·Û‚ÂÛÙ›Ô˘, ÏfiÁˆ Ù˘ ÌÔÚÊÔÏÔÁ›·˜ ÙÔ˘˜ Î·È Ù˘ ·ÂÏ¢ı¤ÚˆÛ˘ ÈfiÓÙˆÓ ·Û‚ÂÛÙ›Ô˘ Î·È ÊˆÛÊfiÚÔ˘, ·ÔÙÂÏÔ‡Ó ˘Ú‹Ó˜ ηٷÎÚ‹ÌÓÈÛ˘ ··Ù›ÙË, Ô˘ ¿ÁÔ˘Ó ÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Û ·ÙÙ·Ú· Ô˘ ·Ú¿ÁÔ˘Ó ÂÓ·Û‚ÂÛÙȈ̤ÓÔ˘˜ ÈÛÙÔ‡˜15. K·Ù¿ ÙË ÌÔÚÊÔÁ¤ÓÂÛË ÙˆÓ Ô‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ, ÚÈÓ ·fi ÙÔ Û¯ËÌ·ÙÈÛÌfi ÔÛÙ½Ó˘, Ù· ·ÙÙ·Ú· ÙÔ˘ Ô‰ÔÓÙÔı˘Ï·Î›Ô˘ ‰ÈÂÈÛ‰‡Ô˘Ó ÛÙÔ ·ÔÛ˘ÓÙÂıÂÈ̤ÓÔ ÂÈıËÏÈ·Îfi ¤Ï˘ÙÚÔ Hellenic Stomatological Review 57: 39-71, 2013 the risk of rejection by the recipient’s immune system, due to possible major histocompatibility complex (MHC) mismatching between the cells and the recipient organism28. Though, it has been shown that mesenchymal stem cells have low immunogenicity, since culture of human periodontal ligament-derived mesenchymal stem cells with allogenic peripheral blood mononuclear cells did not induce mononuclear cell proliferation29. Furthermore, mesenchymal stem cells have the ability to suppress immune response. It has been found that culture of human periodontal ligament-derived mesenchymal stem cells with allogenic peripheral blood mononuclear cells, that had been stimulated by a mitogenic agent or had been co-cultured with allogenic mononuclear cells, led to a dose-dependent inhibition of mononuclear cell proliferation28. At the highest dose, almost complete inhibition of their proliferation was noted. The authors claimed that mononuclear cell proliferation inhibition was due to cell division prevention, following interaction between mononuclear cells and mesenchymal stem cells rather than to cell apoptosis28. Specifically, it was suggested that mononuclear cell proliferation was mainly inhibited by mesenchymal stem cell-released factors after stimulation by mononuclear cells rather than by mere contact with them. Intrerferon-Á, which is released by T-cells after stimulation by a mitogenic agent or exposure to an antigen to which they have been sensitized, has been found to stimulate the release of such agents by bone marrow-derived mesenchymal stem cells. In Wada et al.’s study28 mesenchymal stem cells were cultured in the presence of interferon-Á, which had been produced by mononuclear cells stimulated by a mitogenic agent. Culturing mononuclear cells in this medium resulted in partial suppression of the proliferation. Contrary to this, in the absence of interferon-Á the proliferation of mononuclear cells cultured in mesenchymal stem cell medium was not suppressed. This indicates that interferon-Á, secreted by mononuclear cells, is partially responsible for the suppression of the proliferation of mononuclear cells by mesenchymal stem cells. Moreover, the expression of transforming growth factor-1(TGF-1), hepatocyte growth factor (HGF) and indoleamine 2,3-dioxygenase(IDO), which are involved in the mesenchymal stem cell immunosuppressive effect, has been found to increase in periodontal ligament-derived mesenchymal stem cells cultured with mononuclear cells29. Interestingly, the expression of indoleamine 2,3-dioxygenase, contrary to the other factors, increased after mesenchymal stem cell culture in the presence of interferon-Á, which indicates that indoleamine 2,3-dioxygenase production is promoted by interferon-Á released by mononuclear cells. Suppression of the mononuclear cell proliferation by mesenchymal stem cells has been reversed, since isolation of mononuclear cells and re-stimulation by a mitogenic agent triggered rapid proliferation29. The immunosuppressive properties of mesenchymal stem cells seem to be of particular significance for their application in perio51 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Ù˘ Ú›˙·˜ ÙÔ˘ Hertwig Î·È ¤Ú¯ÔÓÙ·È Û ·ʋ Ì ÙË ÌË ÂÓ·Û‚ÂÛÙȈ̤ÓË ıÂ̤ÏÈ· Ô˘Û›· Ù˘ Ô‰ÔÓÙ›Ó˘ Ù˘ Ú›˙·˜. OÈ Wen Î·È Û˘Ó.26 ‰ÈÂÚ¢ÓÒÓÙ·˜ ÙËÓ Â›‰Ú·ÛË Ù˘ ·ʋ˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ Ô‰ÔÓÙÔı˘Ï·Î›Ô˘ Ì ÙË ıÂ̤ÏÈ· Ô˘Û›· Ù˘ Ô‰ÔÓÙ›Ó˘ ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÔÛÙÂ˚ÓÔ‚Ï·ÛÙÒÓ Î·È ÙÔ Û¯ËÌ·ÙÈÛÌfi ÔÛÙ½Ó˘, ÌÂϤÙËÛ·Ó ÙË ‰È·ÊÔÚÔÔ›ËÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡ Ô˘ ηÏÏÈÂÚÁ‹ıËÎ·Ó Û ıÚÂÙÈÎfi ˘ÏÈÎfi ηÏÏȤÚÁÂÈ·˜ ΢ÙÙ¿ÚˆÓ ÙÔ˘ Ô‰ÔÓÙÔı˘Ï·Î›Ô˘ ÛÙÔ ÔÔ›Ô ÚÔÛÙ¤ıËÎ·Ó ÌË ÎÔÏÏ·ÁÔÓÔ‡¯Â˜ Ô‰ÔÓÙÈÓÈΤ˜ ÚˆÙ½Ó˜. T· ·ÙÙ·Ú· ÌÂÙ·Û¯ËÌ·Ù›ÛÙËÎ·Ó ·fi ·ÙÚ·ÎÙÔÂȉ‹ Û ›‰· ·ÙÙ·Ú· ΢‚ÔÂȉԇ˜ ‹ ÔÏ˘ÁˆÓÈÎÔ‡ Û¯‹Ì·ÙÔ˜, ·ÚfiÌÔÈÔ˘ Ì ·˘ÙÔ‡ ÙˆÓ ÔÛÙÂ˚ÓÔ‚Ï·ÛÙÒÓ. ¶·Ú·ÙËÚ‹ıËΠηٷÛÙÔÏ‹ ÙÔ˘ ÔÏÏ·Ï·ÛÈ·ÛÌÔ‡ ÙˆÓ Î˘ÙÙ¿ÚˆÓ Î·È ÚÔ·ÁˆÁ‹ Ù˘ ‰È·ÊÔÚÔÔ›ËÛ‹ ÙÔ˘˜. T· ·ÙÙ·Ú· ·ÚÔ˘Û›·Û·Ó ˘„ËÏ‹ ‰Ú·ÛÙËÚÈfiÙËÙ· ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘ Î·È Û¯ËÌ·ÙÈÛÌfi ÂÓ·Û‚ÂÛÙÈˆÌ¤ÓˆÓ ÂÛÙÈÒÓ ÂÓÒ ·ÓȯÓ‡ÙËηÓ, ÛÂ Â›Â‰Ô mRNA Î·È ÚˆÙÂ˚ÓÒÓ, ‰Â›ÎÙ˜ ÂÓ·Û‚ÂÛÙ›ˆÛ˘, Ô˘ ÂÎÊÚ¿˙ÔÓÙ·È Î˘Ú›ˆ˜ ÛÙÔ˘˜ ÛÎÏËÚÔ‡˜ Ô‰ÔÓÙÈÎÔ‡˜ ÈÛÙÔ‡˜ ·fi ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜, Ô‰ÔÓÙÈÓÔ‚Ï¿ÛÙ˜ ‹ ·‰·Ì·ÓÙÈÓÔ‚Ï¿ÛÙ˜, fiˆ˜ ÛÈ·ÏÔÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡, ÔÛÙÂÔÓÂÎÙ›ÓË, ÔÛÙÂÔηÏÛ›ÓË, ÔÛÙÂÔÔÓÙ›ÓË Î·È ÎÔÏÏ·ÁfiÓÔ Ù‡Ô˘ I. øÛÙfiÛÔ ·ÓȯÓ‡ıËÎÂ Ë ÂȉÈ΋ ÁÈ· ÙȘ ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ ÚˆÙ½ÓË Û‡Ó‰ÂÛ˘ ÔÛÙ½Ó˘ ÂÓÒ ‰ÂÓ ·ÓȯÓ‡ÙËΠÙÔ ÂȉÈÎfi ÁÈ· ÙȘ Ô‰ÔÓÙÈÓÔ‚Ï¿ÛÙ˜ ÁÔÓ›‰ÈÔ Ô‰ÔÓÙÈÓÈ΋˜ ÛÈ·ÏÔʈÛÊÔÚˆÙ½Ó˘, ÙÔ ÔÔ›Ô Îˆ‰ÈÎÔÔÈ› ‰‡Ô ·ÚȘ ÌË ÎÔÏÏ·ÁÔÓÔ‡¯Â˜ ÚˆÙ½Ó˜ Ù˘ ıÂ̤ÏÈ·˜ Ô˘Û›·˜ Ù˘ Ô‰ÔÓÙ›Ó˘, ÙËÓ Ô‰ÔÓÙÈÓÈ΋ ÛÈ·ÏÔÚˆÙ½ÓË Î·È ÊˆÛÊÔÚˆÙ½ÓË. OÈ Wen Î·È Û˘Ó.26 Û˘Ì¤Ú·Ó·Ó, ÂÔ̤ӈ˜, ˆ˜ Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ‰È·ÊÔÚÔÔÈ‹ıËÎ·Ó Û ·ÙÙ·Ú· Ì ¯·Ú·ÎÙËÚÈÛÙÈο ÔÛÙÂ˚ÓÔ‚Ï·ÛÙÒÓ. K›Ó‰˘ÓÔ˜ ηÚÎÈÓÔÁ¤ÓÂÛ˘ ·fi Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· H ÈηÓfiÙËÙ· ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Ó· ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û ·ÙÙ·Ú· ‰È·ÊÔÚÂÙÈÎÒÓ ÛÂÈÚÒÓ ÂÓ¤¯ÂÈ ÙÔÓ Î›Ó‰˘ÓÔ Î·ÚÎÈÓÔÁ¤ÓÂÛ˘. TÔ Â›‰Ô˜ ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘fiÌÂÓˆÓ Î˘ÙÙ¿ÚˆÓ Î·È ÙÔ ÂÚÈ‚¿ÏÏÔÓ Ù˘ ‰¤ÎÙÚÈ·˜ ÂÚÈÔ¯‹˜ ÂËÚ¿˙Ô˘Ó ÙËÓ Èı·ÓfiÙËÙ· ÚfiÎÏËÛ˘ ηÎÔ‹ıÔ˘˜ ÓÂÔÏ·Û›·˜27. ™ÙË ‚È‚ÏÈÔÁÚ·Ê›· ‰ÂÓ ¤¯ÂÈ ·Ó·ÊÂÚı› ηÚÎÈÓÔÁ¤ÓÂÛË ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÛÙ· Ï·›ÛÈ· Ù˘ ÚÔÛ¿ıÂÈ·˜ ·Ó¿Ï·Û˘ ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ. Œ¯ÂÈ ˘ÔÛÙËÚȯı› fiÙÈ Î·ÏÏȤÚÁÂÈ· ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ, Û ̤ÛÔ Ô˘ ÚÔ¿ÁÂÈ ÙË ‰È·ÊÔÚÔÔ›ËÛ‹ ·˘ÙÒÓ ÛÂ Û˘ÁÎÂÎÚÈ̤ÓÔ Â›‰Ô˜ ΢ÙÙ¿ÚˆÓ, ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘Û‹ ÙÔ˘˜ ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ ‚Ï¿‚˘ Â›Ó·È ‰˘Ó·Ùfi Ó· ÌÂÈÒÛÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ·˘Ùfi27. AÓÙÈÁÔÓÈÎfiÙËÙ· Î·È ·ÓÔÛÔÚÚ˘ıÌÈÛÙÈΤ˜ ȉÈfiÙËÙ˜ ÙˆÓ ·ÏÏÔÁÂÓÒÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ T· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÌÔÚÔ‡Ó Ó· Â›Ó·È ·˘ÙÔÁÂÓÔ‡˜ ‹ ·ÏÏÔÁÂÓÔ‡˜ ÚÔ¤Ï¢Û˘. T· ·˘ÙÔÁÂÓ‹ ‰ÂÓ ÚÔηÏÔ‡Ó ·ÓÔÛÔÏÔÁÈ΋ ·¿ÓÙËÛË ·fi ÙÔÓ ÍÂÓÈÛÙ‹. øÛÙfiÛÔ, Â›Ó·È ·ÌÊ›‚ÔÏË Ë ÈηÓfiÙËÙ¿ ÙÔ˘˜ Ó· ·Ú¿ÁÔ˘Ó Â·Ú΋ ·ÚÈıÌfi ΢ÙÙ¿ÚˆÓ ÂÍ·ÈÙ›·˜ Ù˘ ‰È·ÊÔÚ¿˜ ÙÔ˘ ‰˘52 dontal tissue regeneration, since immune response activation might negatively affect the therapeutic result. Mesenchymal stem cells derived from inflammed tissues The granulation tissue surgically excised from periodontal defects during phase II periodontal treatment (surgical periodontal treatment) contains numerous mesenchymal stem cells. Mesencymal stem cells have been isolated from granulation tissue removed from intraosseous periodontal defects15. Comparison between cultured mesenchymal stem cells derived from granulation tissue isolated from intraosseous periodontal defects and cultured mesenchymal stem cells derived from healthy periodontium showed similar cell proliferation but statistically significant different cell migration, with mesenchymal stem cells derived from affected periodontium presenting higher migration15. In healthy periodontium, mesenchymal stem cells were restricted to the paravascular area. Contrary to this, in periodontal defects mesenchymal stem cells were located in the extravascular area close to the cementum, where they might have migrated under the effect of inflammatory mediators released by inflamed periodontal tissues. Inflammatory mediators may enhance cell migration, though the exact mechanism is yet to be clarified. Furthermore, statistically significant lower mineralization was noted while following subcutaneous implantation of mesenchymal stem cells isolated from periodontal defects in immunodeficient mice statistically significant lower cementum formation was noted. Inflammation is likely to inhibit cell differentiation, however the effect of agents enhancing cell differentiation might overcome this15. GENE THERAPY Techniques Genetic material can be introduced into target-cells either directly or indirectly. In the direct technique, genetic material is directly transferred to the target-cells of the organism (in-vivo technique). In the indirect technique, genetic material is transferred to target cells that have been isolated from the organism, have been cultured and after introducing the genetic material into them they are re-implanted into the organism (in-vitro technique)3, 30 (Fig. 1). Genetic material vectors Genetic material is transferred to target-cells via vectors. Viruses can be used as genetic material vectors, such as retroviruses, lentiviruses, adenoviruses and adenoassociated viruses. For retroviruses, the genetic material is single-stranded RNA which, after being transcribed into DNA in the host cell, is incorporated into the host cellular genome. Therefore, the cells deriving from the host cell proliferation contain the viral genetic material, thus enabling sustained Hellenic Stomatological Review 57: 39-71, 2013 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Ó·ÌÈÎÔ‡ ·‡ÍËÛ˘ Î·È ‰È·ÊÔÚÔÔ›ËÛ˘ ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÌÂٷ͇ ÙˆÓ ·ÙfïÓ. T· ·ÏÏÔÁÂÓ‹ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ¤¯Ô˘Ó ηıÔÚÈṲ̂ÓÔ ·Ó·Ï·ÛÙÈÎfi ‰˘Ó·ÌÈÎfi. EÓ¤¯Ô˘Ó, fï˜, ÙÔÓ Î›Ó‰˘ÓÔ ·fiÚÚȄ˘ ·fi ÙÔ ·ÓÔÛÔÏÔÁÈÎfi Û‡ÛÙËÌ· ÙÔ˘ ‰¤ÎÙË, ÏfiÁˆ Èı·Ó‹˜ ·Û˘Ì‚·ÙfiÙËÙ·˜ ÌÂٷ͇ ÙÔ˘ Ì›˙ÔÓÔ˜ Û˘ÌϤÁÌ·ÙÔ˜ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ Î·È ÙÔ˘ ‰¤ÎÙË ÔÚÁ·ÓÈÛÌÔ‡28. ¶·Ú’ fiÏ· ·˘Ù¿, ¤¯ÂÈ ‰Âȯı› ˆ˜ Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ‰È·ı¤ÙÔ˘Ó ¯·ÌËÏ‹ ·ÓÙÈÁÔÓÈÎfiÙËÙ· ηıÒ˜ ηÏÏȤÚÁÂÈ· ·ÓıÚÒÈÓˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÙÔ˘ ÂÚÈÚÚÈ˙›Ô˘ Ì ·ÏÏÔÁÂÓ‹ ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú· ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ‰ÂÓ ÚÔοÏÂÛ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙˆÓ ÌÔÓÔ‡ÚËÓˆÓ Î˘ÙÙ¿ÚˆÓ29. EÈÚfiÛıÂÙ·, Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· Ó· ηٷÛÙ¤ÏÏÔ˘Ó ÙËÓ ·ÓÔÛÔÏÔÁÈ΋ ·¿ÓÙËÛË. Œ¯ÂÈ ‚ÚÂı› fiÙÈ Î·ÏÏȤÚÁÂÈ· ·ÓıÚÒÈÓˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ÙÔ˘ ÂÚÈÚÚÈ˙›Ô˘ Ì ·ÏÏÔÁÂÓ‹ ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú· ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ Ô˘ ›¯·Ó ‰ÈÂÁÂÚı› Ì ÌÈÙÔÁfiÓÔ ·Ú¿ÁÔÓÙ· ‹ Û˘ÁηÏÏÈÂÚÁËı› Ì ·ÏÏÔÁÂÓ‹ ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú· ÚÔοÏÂÛ ‰ÔÛÔÂÍ·ÚÙÒÌÂÓË ·Ó·ÛÙÔÏ‹ ÙÔ˘ ÔÏÏ·Ï·ÛÈ·ÛÌÔ‡ ÙˆÓ ÌÔÓÔ‡ÚËÓˆÓ Î˘ÙÙ¿ÚˆÓ28. ™ÙËÓ ˘„ËÏfiÙÂÚË ‰fiÛË Ô˘ ÌÂÏÂÙ‹ıËÎÂ, ‰È·ÈÛÙÒıËΠۯ‰fiÓ Ï‹Ú˘ ·Ó·ÛÙÔÏ‹ ÙÔ˘ ÔÏÏ·Ï·ÛÈ·ÛÌÔ‡ ÙÔ˘˜. ™Â ·˘Ù‹ ÙË ÌÂϤÙË28 ˘ÔÛÙËÚ›¯ıËΠfiÙÈ Ë ·Ó·ÛÙÔÏ‹ ÙÔ˘ ÔÏÏ·Ï·ÛÈ·ÛÌÔ‡ ÙˆÓ ÌÔÓÔ‡ÚËÓˆÓ Î˘ÙÙ¿ÚˆÓ ÔÊÂÈÏfiÙ·Ó Û ·ÚÂÌfi‰ÈÛË Ù˘ ΢ÙÙ·ÚÈ΋˜ ‰È·›ÚÂÛ˘ ‡ÛÙÂÚ· ·fi ·ÏÏËÏ›‰Ú·ÛË ÙÔ˘˜ Ì ٷ ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Î·È fi¯È Û ·fiÙˆÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ. ™˘ÁÎÂÎÚÈ̤ӷ, ˘ÔÛÙËÚ›¯ıËΠfiÙÈ Ô ÔÏÏ·Ï·ÛÈ·ÛÌfi˜ ÙˆÓ ÌÔÓÔ‡ÚËÓˆÓ Î˘ÙÙ¿ÚˆÓ ·Ó·ÛÙ¿ÏıËΠ΢ڛˆ˜ ·fi ·Ú¿ÁÔÓÙ˜ Ô˘ ·ÂÏ¢ı¤ÚˆÛ·Ó Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ηÙfiÈÓ ‰È¤ÁÂÚÛ˘ ·fi Ù· ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú· Î·È fi¯È ·fi ·Ï‹ ·ʋ ÙÔ˘˜ Ì ·˘Ù¿. H ÈÓÙÂÚÊÂÚfiÓË-Á, Ô˘ ·ÂÏ¢ıÂÚÒÓÂÙ·È ·fi T·ÙÙ·Ú· ηÙfiÈÓ ‰È¤ÁÂÚÛ‹˜ ÙÔ˘˜ Ì ÌÈÙÔÁfiÓÔ ·Ú¿ÁÔÓÙ· ‹ ¤ÎıÂÛ‹˜ ÙÔ˘˜ Û ·ÓÙÈÁfiÓÔ ÛÙÔ ÔÔ›Ô ¤¯Ô˘Ó ¢·ÈÛıËÙÔÔÈËı›, ¤¯ÂÈ ‚ÚÂı› fiÙÈ ‰ÈÂÁ›ÚÂÈ Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÙÔ˘ Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ ÛÙËÓ ·ÂÏ¢ı¤ÚˆÛË Ù¤ÙÔÈˆÓ ·Ú·ÁfiÓÙˆÓ. ™ÙË ÌÂϤÙË ÙˆÓ Wada Î·È Û˘ÓÂÚÁ·ÙÒÓ28, ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ηÏÏÈÂÚÁ‹ıËÎ·Ó ·ÚÔ˘Û›· ÈÓÙÂÚÊÂÚfiÓ˘-Á Ô˘ ·Ú¿¯ıËΠ·fi ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú· ÌÂÙ¿ ·fi ‰È¤ÁÂÚÛ‹ ÙÔ˘˜ Ì ÌÈÙÔÁfiÓÔ ·Ú¿ÁÔÓÙ·. K·ÏÏȤÚÁÂÈ· ÌÔÓÔ‡ÚËÓˆÓ Î˘ÙÙ¿ÚˆÓ ÛÙÔ ıÚÂÙÈÎfi ˘ÏÈÎfi ·˘Ù‹˜ Ù˘ ηÏÏȤÚÁÂÈ·˜ ·Ó¤ÛÙÂÈÏ ÌÂÚÈÎÒ˜ ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙÔ˘˜. AÓÙ›ıÂÙ·, ‰ÂÓ ·Ú·ÙËÚ‹ıËΠ·Ó·ÛÙÔÏ‹ ÙÔ˘ ÔÏÏ·Ï·ÛÈ·ÛÌÔ‡ ÌÔÓÔ‡ÚËÓˆÓ Î˘ÙÙ¿ÚˆÓ Ô˘ ηÏÏÈÂÚÁ‹ıËÎ·Ó Û ıÚÂÙÈÎfi ˘ÏÈÎfi ηÏÏȤÚÁÂÈ·˜ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ·Ô˘Û›· ÈÓÙÂÚÊÂÚfiÓ˘-Á, ÁÂÁÔÓfi˜ Ô˘ Ô‰‹ÁËÛ ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ Ë ÈÓÙÂÚÊÂÚfiÓË-Á Ô˘ ÂÎÎÚ›ÓÂÙ·È ·fi Ù· ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú· ¢ı‡ÓÂÙ·È ÌÂÚÈÎÒ˜ ÁÈ· ÙËÓ ·Ó·ÛÙÔÏ‹ ÙÔ˘ ÔÏÏ·Ï·ÛÈ·ÛÌÔ‡ ÙÔ˘˜ ·fi Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú·. E›Û˘, Ë ¤ÎÊÚ·ÛË ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·-1 (TGF-1), ÙÔ˘ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· (HGF) Î·È Ù˘ ÈÓ‰ÔÏ·̛Ó˘ 2,3-‰ÈÔ͢ÁÂÓ¿Û˘ (IDO), ·Ú·ÁfiÓÙˆÓ Ô˘ ¤¯ÂÈ ‚ÚÂı› fiÙÈ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋ ‰Ú¿ÛË ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ, ‚Ú¤ıËΠӷ ·˘Í¿ÓÂÙ·È ÛÙ· Hellenic Stomatological Review 57: 39-71, 2013 Figure 1: Gene transfer in periodontal defects via direct or indirect technique (modified from Rios et al3). gene expression. Arbitrary introduction of the viral genetic material into the host cellular genome may cause gene mutagenesis resulting in carcinogenesis. Most retroviruses affect dividing cells only3, 30. Lentiviruses comprise a distinct retrovirus type characterized by long incubation time. Their genetic material is being incorporated into the host cell genome as well. Although the introduction sites of their genetic material are more restricted, carcinogenesis is possible. Furthermore, for lentiviruses there is a high replication risk, after genetic material incorporation into the host cell genome. Lentiviruses can affect both dividing and non-dividing cells3. For adenoviruses, the genetic material is doublestranded DNA, which does not get incorporated into the host cellular genome, resulting in transient gene expression and no risk of carcinogenesis. The affected cells do not present phenotypic changes3, 30. In order to eliminate the risk of replication and production of harmful agents by adenoviruses used as genetic material vectors, removal of the E1 gene, which is necessary for the replication and expression of viral genes, from their genome has been suggested31. There is a risk of host immune reaction to viral capsid proteins, since they are not surrounded by an envelope. The application of the indirect technique, where adenoviral genetic material is transferred in-vitro to target-cells, prevents this32. They affect both dividing and non-dividing cells3. Adeno-associated viruses derive from parvoviruses. Their genetic material is single-stranded DNA, which gets incorporated into the host cellular genome. It is introduced in a specific site of the human genome, although arbitrary introduction cannot be excluded. They affect both dividing and non-dividing cells. They have not been related to any known human disease, they have low immunogenicity but their small size does not permit transfer of genetic material greater than 5kb3, 30. Moreover, plasmids, DNA polymers, peptides and lipids have been used as vectors for gene transfer. Their ability 53 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÚÚÈ˙›Ô˘ ÌÂÙ¿ ·fi ηÏÏȤÚÁÂÈ¿ ÙÔ˘˜ Ì ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú·29. M¿ÏÈÛÙ·, Ë ¤ÎÊÚ·ÛË Ù˘ ÈÓ‰ÔÏ·̛Ó˘ 2,3-‰ÈÔ͢ÁÂÓ¿Û˘, Û ·ÓÙ›ıÂÛË Ì ÙÔ˘˜ ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜, ·˘Í‹ıËΠÌÂÙ¿ ·fi ηÏÏȤÚÁÂÈ· ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ·ÚÔ˘Û›· ÈÓÙÂÚÊÂÚfiÓ˘-Á, ÁÂÁÔÓfi˜ Ô˘ Ô‰‹ÁËÛ ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ Ë ·Ú·ÁˆÁ‹ Ù˘ ÈÓ‰ÔÏ·̛Ó˘ 2-3 ‰ÈÔ͢ÁÂÓ¿Û˘ ÚÔ¿ÁÂÙ·È ·fi ÙËÓ ·ÂÏ¢ıÂÚÔ‡ÌÂÓË ·fi Ù· ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú· ÈÓÙÂÚÊÂÚfiÓË-Á. Œ¯ÂÈ ·Ú·ÙËÚËı› ˆ˜ Ë Î·Ù·ÛÙÔÏ‹ ÙÔ˘ ÔÏÏ·Ï·ÛÈ·ÛÌÔ‡ ÌÔÓÔ‡ÚËÓˆÓ Î˘ÙÙ¿ÚˆÓ ·fi ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ‹Ù·Ó ·ÓÙÈÛÙÚÂÙ‹ ηıÒ˜ ·ÔÌfiÓˆÛË ÙÔ˘˜ Î·È ÂÎ Ó¤Ô˘ ‰È¤ÁÂÚÛË ÙÔ˘˜ Ì ÌÈÙÔÁfiÓÔ ·Ú¿ÁÔÓÙ· ÚÔοÏÂÛ ٷ¯‡Ú˘ıÌÔ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙÔ˘˜29. OÈ ·ÓÔÛÔηٷÛÙ·ÏÙÈΤ˜ ȉÈfiÙËÙ˜ ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Ê·›ÓÂÙ·È Ó· ¤¯Ô˘Ó ȉȷ›ÙÂÚË ÛËÌ·Û›· ÁÈ· ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙÔ˘˜ ÛÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ, ηıÒ˜ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Ì˯·ÓÈÛÌÔ‡ Ù˘ ·ÓÔÛÔÏÔÁÈ΋˜ ·¿ÓÙËÛ˘ Â›Ó·È ‰˘Ó·Ùfi Ó· ¤¯ÂÈ ·ÚÓËÙÈΤ˜ ÂÈÙÒÛÂȘ ÛÙÔ ıÂڷ¢ÙÈÎfi ·ÔÙ¤ÏÂÛÌ·. MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ·fi ÊÏÂÁÌ·›ÓÔÓÙ˜ ÈÛÙÔ‡˜ O ÎÔÎÎÈ҉˘ ÈÛÙfi˜ Ô˘ ·ÔÌ·ÎÚ‡ÓÂÙ·È ·fi ÙȘ ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ ηٿ ÙË Ê¿ÛË ·ÔηٿÛÙ·Û˘ ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ‚Ï·‚ÒÓ (¯ÂÈÚÔ˘ÚÁÈ΋ ÂÚÈÔ‰ÔÓÙÈ΋ ıÂڷ›·) ÂÚȤ¯ÂÈ ÛËÌ·ÓÙÈÎfi ·ÚÈıÌfi ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ. MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ¤¯Ô˘Ó ·ÔÌÔÓˆı› ·fi ÎÔÎÎÈÒ‰Ë ÈÛÙfi Ô˘ ·Ê·ÈÚ¤ıËΠ·fi ÂÓ‰ÔÛÙÈΤ˜ ‚Ï¿‚˜ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ·ÛıÂÓÒÓ15. ™‡ÁÎÚÈÛË ÌÂٷ͇ ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Ô˘ ÚÔ¤Ú¯ÔÓÙ·Ó ·fi ÎÔÎÎÈÒ‰Ë ÈÛÙfi ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÂÓ‰ÔÛÙÈÎÒÓ ‚Ï·‚ÒÓ Î·È ·˘ÙÒÓ Ô˘ ÚÔ¤Ú¯ÔÓÙ·Ó ·fi ˘ÁȤ˜ ÂÚÈÔ‰fiÓÙÈÔ ¤‰ÂÈÍÂ, ÌÂÙ¿ ·fi ηÏÏȤÚÁÂÈ¿ ÙÔ˘˜, ·ÚfiÌÔÈÔ ÔÏÏ·Ï·ÛÈ·ÛÌfi ·ÏÏ¿ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ‰È·ÊÔÚÂÙÈ΋ ÌÂÙ·Ó¿ÛÙ¢ÛË, Ì ˘„ËÏfiÙÂÚË ÌÂÙ·Ó¿ÛÙ¢ÛË ÁÈ· Ù· ·ÙÙ·Ú· ·fi ÙÔ ÚÔۂ‚ÏË̤ÓÔ ÂÚÈÔ‰fiÓÙÈÔ15. ™ÙÔ ˘ÁȤ˜ ÂÚÈÔ‰fiÓÙÈÔ, Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÂÚÈÔÚ›˙ÔÓÙ·Ó ÛÙÔÓ ÂÚÈ·ÁÁÂÈ·Îfi ¯ÒÚÔ. AÓÙ›ıÂÙ·, ÛÙȘ ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜, ÌÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· ÂÓÙÔ›˙ÔÓÙ·Ó ÛÙÔÓ Â͈·ÁÁÂÈ·Îfi ¯ÒÚÔ Î·È ÎÔÓÙ¿ ÛÙËÓ ÔÛÙ½ÓË, fiÔ˘ ÌÂÙ·Ó·ÛÙÂ‡Ô˘Ó Èı·Ó¿ ˘fi ÙËÓ Â›‰Ú·ÛË ÌÂÛÔÏ·‚ËÙÒÓ Ù˘ ÊÏÂÁÌÔÓ‹˜ Ô˘ ·ÂÏ¢ıÂÚÒÓÔÓÙ·È ·fi ÙÔ˘˜ ÊÏÂÁÌ·›ÓÔÓÙ˜ ÂÚÈÔ‰ÔÓÙÈÎÔ‡˜ ÈÛÙÔ‡˜. OÈ ÌÂÛÔÏ·‚ËÙ¤˜ Ù˘ ÊÏÂÁÌÔÓ‹˜ Èı·ÓfiÓ Ó· ÚÔ¿ÁÔ˘Ó ÙË ÌÂÙ·Ó¿ÛÙ¢ÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ, Ô ·ÎÚÈ‚‹˜ Ì˯·ÓÈÛÌfi˜, fï˜, Ì ÙÔÓ ÔÔ›Ô Ú·ÁÌ·ÙÔÔÈÂ›Ù·È ·˘Ùfi ‰ÂÓ ¤¯ÂÈ ·ÎfiÌË ‰È¢ÎÚÈÓÈÛÙ›. E›Û˘, ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚË ÂÓ·Û‚ÂÛÙ›ˆÛË. MÂÙ¿ ·fi ˘Ô‰fiÚÈ· ÂÌʇÙ¢ÛË ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ Ô˘ ·ÔÌÔÓÒıËÎ·Ó ·fi ÙȘ ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ Û ·ÓÔÛÔ·Ó·Ú΋ ÔÓÙ›ÎÈ·, ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚÔ˜ Û¯ËÌ·ÙÈÛÌfi˜ ÔÛÙ½Ó˘. H ‡·ÚÍË ÊÏÂÁÌÔÓ‹˜ Èı·ÓfiÓ ÚÔηÏ› ·Ó·ÛÙÔÏ‹ Ù˘ ‰È·ÊÔÚÔÔ›ËÛ˘ ÙˆÓ Î˘ÙÙ¿ÚˆÓ, Ë ÔÔ›·, fï˜, Â›Ó·È ‰˘Ó·Ùfi Ó· ˘ÂÚÎÂÚ·ÛÙ› ηÙfiÈÓ ‰Ú¿Û˘ ·Ú·ÁfiÓÙˆÓ Ô˘ ÚÔ¿ÁÔ˘Ó ÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ15. 54 to affect the target-cells is significantly reduced in comparison to viral vectors. However, the low immunogenicity, the ability to transfer genetic material irrespective of its size and their massive production makes them a promising alternative option for genetic material transfer to the target-cells. Electroporation and ultrasound waves have also been used for genetic material transfer to the target-cells3, 30. Safety of the viral vector administration Systematic administration of adenoviruses as genetic material vectors may cause acute toxicity and hepatic pathology. It has been found that 99% of systemically administered adenoviruses ends up in the liver, where via the hepatocytes, the Kupffer cells and the blood circulation may be distributed to the lungs and the spleen. Local application reduces systemic dissemination and achieves a more favorable efficiency-toxicity ratio. However systemic dissemination (at 10 min), since the viral vectors might enter the systemic circulation via microvessels, and inflammatory infiltrate within liver (at 15 min) have been reported even after local application. Chang et al.33 found that local application of adenoviruses carrying luciferase gene incorporated into a collagen matrix led to an effective localized therapeutic result. Two weeks after local adenovirus application at a concentration of 5.5x108 pfu/ml the luciferase expression was reduced to non-detectable levels both in the defect area and in any organ. Similar results were reported after local adenovirus application at a concentration of 5.5x109 pfu/ml, though a persistent, weak luciferase expression was detected around the defect in a few rats, which derived from the muscles. Despite the low luciferase expression detected in several organs within the first two weeks, there was no enzyme increase indicative of organ damage. There was no indication of toxicity within the 35 days of the study duration. Genetic material transferred Genes that have been transferred for periodontal tissue regeneration encode growth factors. Studies of direct or indirect transfer of bone morphogenetic protein-2 and -7 (BMP-2 and BMP-7, respectively), basic fibroblast growth factor (bFGF), osteoprotegerin (OPG) and plateletderived growth factor- B (PDGF-B) via viruses or plasmids in periodontal defects of animal models have demonstrated encouraging results (Table 3). Concerning periodontal regeneration, gene transfer aiming at host immune response regulation, in an attempt to ameliorate the conditions of the periodontal tissue environment, has attracted distinct interest. Target-cells might be genetically modified in order to express two or more genes. Genes can be independent, their transcription being regulated by different promoters. In this case, antagonistic reactions might occur among the various promoters. Alternatively, genes may be linked to each other with internal ribosome entry site Hellenic Stomatological Review 57: 39-71, 2013 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review °ONI¢IAKH £EPA¶EIA T¯ÓÈΤ˜ H ÂÈÛ·ÁˆÁ‹ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÛÙ· ·ÙÙ·Ú·-ÛÙfi¯Ô˘˜ ÌÔÚ› Ó· Á›ÓÂÈ ¿ÌÂÛ· ‹ ¤ÌÌÂÛ·. K·Ù¿ ÙËÓ ¿ÌÂÛË Ù¯ÓÈ΋ ÙÔ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ÌÂٷʤÚÂÙ·È ·Â˘ı›·˜ ÛÙ· ·ÙÙ·Ú·-ÛÙfi¯Ô˘˜ ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ (in-vivo Ù¯ÓÈ΋) ÂÓÒ Î·Ù¿ ÙËÓ ¤ÌÌÂÛË Ù¯ÓÈ΋ ÙÔ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ÌÂٷʤÚÂÙ·È Û ·ÙÙ·Ú·ÛÙfi¯Ô˘˜ Ô˘ ¤¯Ô˘Ó ·ÔÌÔÓˆı› ·fi ÙÔÓ ÔÚÁ·ÓÈÛÌfi, ¤¯Ô˘Ó ηÏÏÈÂÚÁËı› Î·È ÌÂÙ¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙÔ˘ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ Û ·˘Ù¿ ·ÓÂÌÊ˘Ù‡ÔÓÙ·È ÛÙÔÓ ÔÚÁ·ÓÈÛÌfi (invitro Ù¯ÓÈ΋)3, 30 (EÈÎ. 1). EÈÎ. 1: MÂÙ·ÊÔÚ¿ ÁÔÓȉ›ˆÓ ÛÙËÓ ÂÚÈÔ‰ÔÓÙÈ΋ ‚Ï¿‚Ë Ì ÙËÓ ¿ÌÂÛË (in-vivo) Î·È ¤ÌÌÂÛË (in-vitro) Ù¯ÓÈ΋ (ÙÚÔÔÔÈË̤ÓÔ ·fi Rios et al3). ºÔÚ›˜ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ H ÌÂÙ·ÊÔÚ¿ ÙÔ˘ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÛÙ· ·ÙÙ·Ú·-ÛÙfi¯Ô˘˜ Á›ÓÂÙ·È Ì¤Ûˆ ‰È·ÊfiÚˆÓ ÊÔÚ¤ˆÓ. ø˜ ÊÔÚ›˜ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ÈÔ›, fiˆ˜ ÚÂÙÚÔ˚Ô›, Ê·ÎÔ˚Ô›, ·‰ÂÓÔ˚Ô› Î·È ÈÔ› Û¯ÂÙÈ˙fiÌÂÓÔÈ Ì ·‰ÂÓÔ˚Ô‡˜. OÈ ÚÂÙÚÔ˚Ô› ¤¯Ô˘Ó ˆ˜ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ÌÔÓfiÎψÓÔ RNA, ÙÔ ÔÔ›Ô ·ÊÔ‡ ÌÂÙ·ÁÚ·Ê› Û DNA ÛÙÔ Î‡ÙÙ·ÚÔ-ÍÂÓÈÛÙ‹, ÂÓۈ̷ÙÒÓÂÙ·È ÛÙÔ ÁÔÓȉ›ˆÌ· ÙÔ˘. A˘Ùfi ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù· ·ÙÙ·Ú· Ô˘ ı· ÚÔ·„Ô˘Ó ·fi ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙÔ˘ ΢ÙÙ¿ÚÔ˘-ÍÂÓÈÛÙ‹ Ó· ÂÚȤ¯Ô˘Ó ÙÔ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ÙÔ˘ ÈÔ‡, ÁÂÁÔÓfi˜ Ô˘ ηıÈÛÙ¿ ‰˘Ó·Ù‹ ÙËÓ ·Ú·ÙÂٷ̤ÓË ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ. øÛÙfiÛÔ, Ë ·˘ı·›ÚÂÙË ÂÈÛ·ÁˆÁ‹ ÙÔ˘ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÙÔ˘ ÈÔ‡ ÛÙÔ ÁÔÓȉ›ˆÌ· ÙÔ˘ ΢ÙÙ¿ÚÔ˘-ÍÂÓÈÛÙ‹ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÌÂÙ¿ÏÏ·ÍË ÁÔÓȉ›ˆÓ Ì ·ÔÙ¤ÏÂÛÌ· ηÚÎÈÓÔÁ¤ÓÂÛË. OÈ ÂÚÈÛÛfiÙÂÚÔÈ ÚÂÙÚÔ˚Ô› ÌÔÚÔ‡Ó Ó· ÚÔÛ‚¿ÏÔ˘Ó ÌfiÓÔ ‰È·ÈÚÔ‡ÌÂÓ· ·ÙÙ·Ú·3, 30. OÈ Ê·ÎÔ˝Ô› ·ÔÙÂÏÔ‡Ó ÂȉÈ΋ ηÙËÁÔÚ›· ÚÂÙÚÔ˚ÒÓ, Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi Ì·ÎÚ‡ ¯ÚfiÓÔ ÂÒ·Û˘. TÔ ÁÂÓÂÙÈÎfi ÙÔ˘˜ ˘ÏÈÎfi ›Û˘ ÂÓۈ̷ÙÒÓÂÙ·È ÛÙÔ ÁÔÓȉ›ˆÌ· ÙÔ˘ ΢ÙÙ¿ÚÔ˘-ÍÂÓÈÛÙ‹. AÓ Î·È ÔÈ ı¤ÛÂȘ ÂÈÛ·ÁˆÁ‹˜ ÙÔ˘ ÁÂÓÂÙÈÎÔ‡ ÙÔ˘˜ ˘ÏÈÎÔ‡ Â›Ó·È ÈÔ ÂÚÈÔÚÈṲ̂Ó˜, ˘¿Ú¯ÂÈ Èı·ÓfiÙËÙ· ηÚÎÈÓÔÁ¤ÓÂÛ˘. E›Û˘, Ô Î›Ó‰˘ÓÔ˜ ·ÓÙÈÁÚ·Ê‹˜ ÙˆÓ Ê·ÎÔ˚ÒÓ ÌÂÙ¿ ÙËÓ ÂÓۈ̿وÛË ÙÔ˘ ÁÂÓÂÙÈÎÔ‡ ÙÔ˘˜ ˘ÏÈÎÔ‡ ÛÙÔ ÁÔÓȉ›ˆÌ· ÙÔ˘ ΢ÙÙ¿ÚÔ˘-ÍÂÓÈÛÙ‹ Â›Ó·È ·˘ÍËHellenic Stomatological Review 57: 39-71, 2013 sequences (IRES sequences), their transcription being regulated by the same promoter. Genes are transcribed to the same mRNA but they are bound to ribosomes via the IRES sequences and are independently translated. Though, it has been reported that the expression of the second gene, which follows the IRES sequence, usually does not exceed the 20-50% of the expression of the first gene31. Bone morphogenetic proteins (BMPs) It has been shown that prolonged exposure to a low concentration of human recombinant bone morphogenetic protein-2 enhances cementogenesis. However, in case of local application in the defect high bone morphogenetic protein-2 (BMP-2) dosages are required, due to short half-life. High concentrations have been associated with increased risk of local complications, such as ankylosis and root resorption. Sustained release from cells that have been genetically modified to express BMP-2 reduced the required concentration by approximately 1,000 times32, 41. Yang et al.31 found that human periodontal ligament cells genetically modified to express bone morphogenetic protein-7 (BMP-7) and insulin-like growth factor-1 (IGF-1) or BMP-7 only, at 3 days presented statistically significant greater BMP-7 expression, alkaline phosphatase activity and collagen type I, Runx2 and bone sialoprotein expression in comparison with periodontal ligament cells genetically modified to express green fluorescent protein (GFP) and non-genetically modified periodontal ligament cells. Cells genetically modified to express BMP-7 and IGF-1 presented statistically significantly greater alkaline phosphatase activity and type I collagen and Runx2 expression in comparison with cells genetically modified to express BMP-7 only. The BMP-7 expression was highest after 9 days for both cell groups, whereas their expression remained statistically significantly higher in comparison to the cells that were genetically modified to express GFP and the non-genetically modified cells up to 27 days31. Platelet-derived growth factor (PDGF) Platelet-derived growth factor-AA (PDGF-AA), which consists of two A chains of PDGF, binding to the PDGFa receptor, a tyrosine kinase receptor, induces its phosphorylation which triggers an intracellular and extracellular signaling cascade. Chen and Giannobile42 infected rat dermal fibroblasts with adenoviruses carrying the PDGF-A chain gene and found PDGFa receptor phosphorylation at 8 hours, which increased till 96 hours, when the last cells to be studied were collected. ERK1/2 and Akt, which are involved in the signaling cascade that PDGFa receptor phosphorylation triggers, presented similar alteration of phosphorylation levels. After human recombinant PDGF-AA administration, PDGFa receptor phosphorylation was maintained till 48 hours but at 72 hours had started to weaken. Similarly, ERK1/2 and Akt 55 56 Rats BMP-7, noggin (antagonist) BMP-2 Beagle dogs Surgicallyinduced periodontal defects (buccal tomandibularpremolar mesial root, U-shaped defects) Mandibular alveolar defects BMP-2 New Zealand rabbits Surgicallyinduced periodontal defects Gene Animal Defect Adenoviru s Plasmids Adenovirus Vector Dermal fibroblast Bone marrowderived mesenchymal stem cells Target-cells Ex-vivo Gelatin - Pluronic F127 Ex-vivo In-vivo Vehicle Technique - 8 weeks - Duration Rapid osteogenesis, cementogenesis and predictable regene-ration. Suppression of osteogenesis by noggin-expressing cells. Complete bone regeneration and fibers and vessel-rich connective tissue creation. Statistically significantly highercementum, connective tissue and bone creationas compared to saline application, similar to human recombinant BMP-2 application. Cementum and Sharpey’s fibers creation. Statistically significantly higher bone creation compared to non- genetically modified cell transplantation and vehicle only application. Results Table 3: Gene transfer studies for periodontal and peri-implant tissue regeneration in animal models. 32 35 34 Study μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Hellenic Stomatological Review 57: 39-71, 2013 Fibroblast basic growth factor and GFP BMP-7 BMP-7 Beagle dogs Beagle dogs - Furcation defects Surgicallyinduced class II furcation defects Mandibular peri-implant defects Hellenic Stomatological Review 57: 39-71, 2013 Adenovirus - Eukaryotic plasmid pDC316 12 weeks Collagen membrane Chitosan/ collagen/ periodontal ligament cells Ex-vivo In-vivo Bone marrowderived stromal cells 3 months 6 weeks Ex-vivo Bone marrow derived mesenchymal stromal cells Higher alkalinephosphatase activity, osteopontin and sialoprotein expression by vehicle cells prior to application and higher bone creationafter 4 and 8 weeks as compared to vehicle application alone, without adenoviruses carrying BMP-7 gene. Statistically significantly greater newly-created bone area and newlycreated cementum length as compared to no transplantation and non-genetically modified cell transplantation, which presented statistically significantly differences as compared to no cell transplantation. Statistically significantly higher bone regeneration rate as compared to nongenetically modified cell transplantation. 38 37 36 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review 57 Osteoprotegerin PDGF-B chain BMP-2 Dogs Rats Beagle dogs Surgicallyinduced premolar buccal horizon-tal osseous (4x4x3mm) Surgically induced periimplant defects 58 Mandibul molar periodntal defects Adenovirus Adenovirus in concentrations 5.5x108 or 5.5x109 pfu/ml Plasmid Mesenchymal stem cells Bone marrowstromal cells - Collagen matrix In-vivo Ex-vivo PLGA Ex-vivo 8 weeks - 6 weeks Cementum and Sharpey’s fibers creation on cementumdenuded root surfaces in contrast to nongenetically modified cells transplantation, where incomplete healing and localized root resorption were noted. Statistically significantly higher bone creation at 8 weeks. Bone regeneration acceleration as compared to transplantation of cells carrying luciferase gene, similar to hrPDGF-BB administration. The highest adenovirus concentration was more effective. Statistically significantly higher cementum, connective tissue and bone creation as compared to nongenetically modified cell transplantation, vehicle application alone and root scaling alone. 41 40 39 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Hellenic Stomatological Review 57: 39-71, 2013 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ̤ÓÔ˜. OÈ Ê·ÎÔ˚Ô› ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· Ó· ÚÔÛ‚¿ÏÔ˘Ó ‰È·ÈÚÔ‡ÌÂÓ· Î·È ÌË Î‡ÙÙ·Ú·3. OÈ ·‰ÂÓÔ˚Ô› ¤¯Ô˘Ó ˆ˜ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ‰›ÎψÓÔ DNA, ÙÔ ÔÔ›Ô ‰ÂÓ ÂÓۈ̷ÙÒÓÂÙ·È ÛÙÔ ÁÔÓȉ›ˆÌ· ÙÔ˘ ΢ÙÙ¿ÚÔ˘ÍÂÓÈÛÙ‹ Ì ·ÔÙ¤ÏÂÛÌ· Ë ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ Ó· Â›Ó·È ·ÚÔ‰È΋ Î·È Ó· ÌËÓ ˘¿Ú¯ÂÈ Î›Ó‰˘ÓÔ˜ ÚfiÎÏËÛ˘ ηÚÎÈÓÔÁ¤ÓÂÛ˘. T· ·ÙÙ·Ú· Ô˘ ÚÔÛ‚¿ÏÏÔ˘Ó ‰ÂÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó Ê·ÈÓÔÙ˘ÈΤ˜ ·ÏÏ·Á¤˜3, 30. ¶ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂÍ·ÏÂÈÊı› Ô Î›Ó‰˘ÓÔ˜ ·ÓÙÈÁÚ·Ê‹˜ Î·È ·Ú·ÁˆÁ‹˜ ‚Ï·ÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ·‰ÂÓÔ˚ÒÓ Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ÁÈ· ÙËÓ ÚÔÛ‚ÔÏ‹ ΢ÙÙ¿ÚˆÓ-ÛÙfi¯ˆÓ ˆ˜ ÊÔÚ›˜ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡, ¤¯ÂÈ ÌÂÏÂÙËı› Ë ·Ê·›ÚÂÛË ÙÔ˘ ÁÔÓȉ›Ô˘ E1 ·fi ÙÔ ÁÔÓȉ›ˆÌ· ÙˆÓ ·‰ÂÓÔ˚ÒÓ ÙÔ ÔÔ›Ô Â›Ó·È ··Ú·›ÙËÙÔ ÁÈ· ÙËÓ ·ÓÙÈÁÚ·Ê‹ Î·È ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ È˚ÎÒÓ ÁÔÓȉ›ˆÓ31. TÔ ÁÂÁÔÓfi˜ fiÙÈ ‰ÂÓ ÂÚÈ‚¿ÏÏÔÓÙ·È ·fi ¤Ï˘ÙÚÔ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ‡·ÚÍË ÎÈÓ‰‡ÓÔ˘ ÂΉ‹ÏˆÛ˘ ·ÓÔÛÔÏÔÁÈ΋˜ ·ÓÙ›‰Ú·Û˘ ÂÓ¿ÓÙÈ· ÛÙȘ ÚˆÙ½Ó˜ Ù˘ È˚΋˜ ο„·˜. TÔ Úfi‚ÏËÌ· ·˘Ùfi ÌÔÚ› Ó· ·Ú·Î·ÌÊı› Ì ÂÊ·ÚÌÔÁ‹ Ù˘ ¤ÌÌÂÛ˘ Ù¯ÓÈ΋˜, ηٿ ÙËÓ ÔÔ›· ÙÔ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi Ô˘ ʤÚÔ˘Ó ÔÈ ·‰ÂÓÔ˚Ô› ÌÂٷʤÚÂÙ·È in-vitro ÛÙ· ·ÙÙ·Ú·-ÛÙfi¯Ô˘˜32. OÈ ·‰ÂÓÔ˚Ô› ¤¯Ô˘Ó ˘„ËÏ‹ ÈηÓfiÙËÙ· ÚÔÛ‚ÔÏ‹˜ ‰È·ÈÚÔ‡ÌÂÓˆÓ Î·È ÌË ‰È·ÈÚÔ‡ÌÂÓˆÓ Î˘ÙÙ¿ÚˆÓ3. OÈ Û¯ÂÙÈ˙fiÌÂÓÔÈ Ì ·‰ÂÓÔ˚Ô‡˜ ÈÔ› ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙÔ˘˜ ·Ú‚Ô˚Ô‡˜. Œ¯Ô˘Ó ˆ˜ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ÌÔÓfiÎψÓÔ DNA, ÙÔ ÔÔ›Ô ÂÓۈ̷ÙÒÓÂÙ·È ÛÙÔ ÁÔÓȉ›ˆÌ· ÙÔ˘ ΢ÙÙ¿ÚÔ˘ÍÂÓÈÛÙ‹. TÔ ÁÂÓÂÙÈÎfi ÙÔ˘˜ ˘ÏÈÎfi ÂÈÛ¿ÁÂÙ·È ÛÂ Û˘ÁÎÂÎÚÈ̤ÓË ı¤ÛË ÙÔ˘ ·ÓıÚÒÈÓÔ˘ ÁÔÓȉÈÒÌ·ÙÔ˜, ·Ó Î·È ¤¯ÂÈ ·Ú·ÙËÚËı› Î·È ·˘ı·›ÚÂÙË ÂÈÛ·ÁˆÁ‹ ÙÔ˘. ¶ÚÔÛ‚¿ÏÏÔ˘Ó ‰È·ÈÚÔ‡ÌÂÓ· Î·È ÌË ‰È·ÈÚÔ‡ÌÂÓ· ·ÙÙ·Ú·. ¢ÂÓ ¤¯Ô˘Ó Û¯ÂÙÈÛÙ› Ì ÁÓˆÛÙ‹ ÓfiÛÔ ÛÙÔÓ ¿ÓıÚˆÔ, ¤¯Ô˘Ó ¯·ÌËÏ‹ ·ÓÙÈÁÔÓÈÎfiÙËÙ·, ˆÛÙfiÛÔ ÙÔ ÌÈÎÚfi ÙÔ˘˜ ̤ÁÂıÔ˜ ‰ÂÓ ÂÈÙÚ¤ÂÈ ÙË ÌÂÙ·ÊÔÚ¿ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÌÂÁ¤ıÔ˘˜ ÌÂÁ·Ï‡ÙÂÚÔ˘ ·fi 5kb3, 30. ÕÏÏÔÈ ÊÔÚ›˜ Ô˘ ¤¯Ô˘Ó ¯ÚËÛÈÌÔÔÈËı› ÁÈ· ÙË ÌÂÙ·ÊÔÚ¿ ÁÔÓȉ›ˆÓ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó Ï·ÛÌ›‰È·, ÔÏ˘ÌÂÚ‹ DNA, ÂÙ›‰È· Î·È ÏÈ›‰È·. A˘ÙÔ› ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛËÌ·ÓÙÈο ÌÂȈ̤ÓË ÈηÓfiÙËÙ· ÚÔÛ‚ÔÏ‹˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ-ÛÙfi¯ˆÓ Û ۯ¤ÛË Ì ÙÔ˘˜ È˚ÎÔ‡˜ ÊÔÚ›˜. øÛÙfiÛÔ, Ë ¯·ÌËÏ‹ ·ÓÔÛÔÁÔÓÈÎfiÙËÙ¿ ÙÔ˘˜, Ë ÈηÓfiÙËÙ· ÌÂÙ·ÊÔÚ¿˜ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ¯ˆÚ›˜ Ó· ˘¿Ú¯ÂÈ ÂÚÈÔÚÈÛÌfi˜ ÛÙÔ Ì¤ÁÂıfi˜ ÙÔ˘ Î·È Ë ‰˘Ó·ÙfiÙËÙ· Ì·˙È΋˜ ·Ú·ÁˆÁ‹˜ ÙÔ˘˜ Ù· ηıÈÛÙ¿ ÌÈ· Èı·Ó‹ ÂÓ·ÏÏ·ÎÙÈ΋ ÂÈÏÔÁ‹. °È· ÙË ÌÂÙ·ÊÔÚ¿ ÙÔ˘ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÛÙ· ·ÙÙ·Ú·-ÛÙfi¯Ô˘˜ ¤¯Ô˘Ó ›Û˘ ¯ÚËÛÈÌÔÔÈËı› Ê˘ÛÈΤ˜ ̤ıÔ‰ÔÈ, fiˆ˜ ËÏÂÎÙÚÔfiÚˆÛË Î·È ˘ÂÚ˯ËÙÈο ·̷ٷ3, 30. AÛÊ¿ÏÂÈ· ¯ÔÚ‹ÁËÛ˘ ÈÈÎÒÓ ÊÔÚ¤ˆÓ H Û˘ÛÙÂÌÈ΋ ¯ÔÚ‹ÁËÛË ·‰ÂÓÔ˚ÒÓ ˆ˜ ÊÔÚ¤ˆÓ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ÔÍ›· ÙÔÍÈÎfiÙËÙ· Î·È ·ıÔÏÔÁ›· ÙÔ˘ ‹·ÙÔ˜. Œ¯ÂÈ ‚ÚÂı› fiÙÈ ÙÔ 99% ÙˆÓ Û˘ÛÙÂÌÈο ¯ÔÚËÁÔ‡ÌÂÓˆÓ ·‰ÂÓÔ˚ÒÓ Î·Ù·Ï‹ÁÂÈ ÛÙÔ ‹·Ú, fiÔ˘ ÚÔÛÏ·Ì‚¿ÓÂÙ·È ·fi Ë·ÙÔ·ÙÙ·Ú· Î·È Î‡ÙÙ·Ú· ÙÔ˘ Kupffer, Ù· ÔÔ›· ̤ۈ Ù˘ ΢ÎÏÔÊÔÚ›·˜ ÌÔÚ› Ó· ‰È·ÓÂÌËıÔ‡Ó ÛÙÔ˘˜ Ó‡ÌÔÓ˜ Î·È ÙÔÓ ÛÏ‹Ó·. H Û˘ÛÙÂÌÈ΋ ‰È·ÛÔÚ¿ ÌÔÚ› Ó· ÌÂȈı› Î·È Ó· ‚ÂÏÙȈı› Ë ·Ó·ÏÔÁ›· ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜-ÙÔÍÈÎfiÙËÙ·˜ Ì ÙÔÈ΋ ÂÊ·ÚÌÔÁ‹ ÙÔ˘˜. øÛÙfiÛÔ, Î·È ÌÂÙ¿ ·fi ÙÔÈ΋ ÂÊ·ÚÌÔÁ‹ ¤¯ÂÈ ·Ó·ÊÂÚı› Û˘ÛÙÂÌÈ΋ ‰È·ÛÔÚ¿ ÌÂÙ¿ ·fi ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Hellenic Stomatological Review 57: 39-71, 2013 phosphorylation was noted at 8 hours and was maintained till 72 and 48 hours respectively. The delay in PDGFa receptor phosphorylation found after infecting the cells with the viruses might be due to the time needed for the gene transfer and expression42. Lin et al.43 after infecting human gingival fibroblasts with adenoviruses carrying PDGF-B chain gene demonsrated PDGF-BB expression at 6 hours, which was sustained at least up to 96 hours. Contrary to the immediate but short-term effect (a few days) of the locally applied recombinant PDGF-BB cell infection with adenoviruses carrying PDGF-B chain resulted in delayed but sustained expression, which was gradually reduced so that on day 14 it reached down to 20% of the highest level40. Giannobile et al.44 infected cementoblasts with viruses carrying PDGF-A chain gene, there was gene exression at 24 hours, which was sustained up to 7 days, when the last cells to be studied were collected. After 24 hours, cementoblasts infected by viruses carrying PDGF-A chain gene presented statistically significantly higher DNA synthesis and statistically significantly lower alkaline phosphatase activity in comparison to cementoblasts genetically modified to express GFP. DNA synthesis and proliferation were at similar levels between cementoblasts infected by viruses carrying PDGF-A chain gene and cementoblasts, where PDGF was continuously applied. On days 4 and 7, cementoblasts genetically modified to express PDGF and cementoblasts to which PDGF was administered demonstrated statistically significant greater increase in number in comparison to cementoblasts genetically modified to express GFP. However, the first group showed statistically significant greater increase in number as compared to the second one. Therefore, the duration of the cell exposure to PDGF seems to affect the periodontal tissue regeneration. It has been claimed that recombinant PDGF application is indicated for defects where rapid initiation of the regeneration process is extremely important, since its short half-life after local application induces cell proliferation and chemotactic cell adhesion without significantly delaying the initiation of their differentiation. Contrary to this, application of adenoviruses carrying PDGF chain gene may be more appropriate for greater defects, where the sustained PDGF effect results in the creation of more cells, though further delaying differentiation initiation40. Regulation of the host immune response Tumor necrosis factor receptor (TNFR) Tumor necrosis factor-a (TNF-a) enhances osseous resorption by stimulating osteoclast differentiation and activation. TNF binds to two receptors (TNFR), namely p55 and p75. Immunomodulatory therapy based on TNF binding has successfully been studied in humans for the management of rheumatoid arthritis by using either monoclonal TNF antibodies or proteins containing TNFR p75 linked to the Fc portion of human IgG145. 59 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review 10 min, ÂÍ·ÈÙ›·˜ Ù˘ ÂÈÛfi‰Ô˘ ÙˆÓ È˚ÎÒÓ ÊÔÚ¤ˆÓ ÛÙË Û˘ÛÙÂÌÈ΋ ΢ÎÏÔÊÔÚ›· Èı·Ó¿ ̤ۈ ÙˆÓ ÙÚȯÔÂȉÒÓ ·ÁÁ›ˆÓ, Î·È ÊÏÂÁÌÔÓ҉˘ ‰È‹ıËÛË ÙÔ˘ ‹·ÙÔ˜ ÌÂÙ¿ ·fi 15 min. OÈ Chung Î·È Û˘Ó.33 ‰È·›ÛÙˆÛ·Ó ˆ˜ ÙÔÈ΋ ¯ÔÚ‹ÁËÛË ·‰ÂÓÔ˚ÒÓ Ô˘ ¤ÊÂÚ·Ó ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ÏÔ˘ÛÈÊÂÚ¿Û˘ ÂÓÛˆÌ·ÙˆÌ¤ÓˆÓ Û ̋ÙÚ· ÎÔÏÏ·ÁfiÓÔ˘ ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ηϿ ÂÓÙÔÈṲ̂ÓË Â›‰Ú·ÛË Ù˘ ıÂڷ›·˜. H ¤ÎÊÚ·ÛË ÏÔ˘ÛÈÊÂÚ¿Û˘ ÌÂÙ¿ ·fi ¯ÔÚ‹ÁËÛË ·‰ÂÓÔ˚ÒÓ ÛÂ Û˘ÁÎÂÓÙÚÒÛÂȘ 5.5x108 pfu/ml ÌÂÈÒıËΠ۠ÌË ·ÓȯÓ‡ÛÈÌ· ›‰· ÛÙËÓ ÂÚÈÔ¯‹ ÙˆÓ ‚Ï·‚ÒÓ ÌÂÙ¿ ·fi 2 ‚‰ÔÌ¿‰Â˜, ¯ˆÚ›˜ Ó· ·ÓȯÓ‡ÂÙ·È Û fiÚÁ·Ó· ÌÂÙ¿ ·fi ·˘Ùfi ÙÔ ‰È¿ÛÙËÌ·. AÓÙ›ÛÙÔȯ· ·ÔÙÂϤÛÌ·Ù· ‰È·ÈÛÙÒıËÎ·Ó Î·È ÌÂÙ¿ ·fi ÙÔÈ΋ ¯ÔÚ‹ÁËÛË ·‰ÂÓÔ˚ÒÓ ÛÂ Û˘ÁΤÓÙÚˆÛË 5.5x109 pfu/ml, ˆÛÙfiÛÔ Û ÔÚÈṲ̂ÓÔ˘˜ Â›Ì˘Â˜ ·ÓȯÓ‡ıËΠÂÌ̤ÓÔ˘Û· ·ÛıÂÓ‹˜ ¤ÎÊÚ·ÛË ÏÔ˘ÛÈÊÂÚ¿Û˘, Ô˘ ÚÔÂÚ¯fiÙ·Ó ·fi ÙÔÓ Ì˘˚Îfi ÈÛÙfi Ô˘ ÂÚȤ‚·Ï ÙËÓ ÂÚÈÔ¯‹ Ù˘ ‚Ï¿‚˘. ¢ÂÓ ·Ú·ÙËÚ‹ıËΠ·‡ÍËÛË ÂÓ˙‡ÌˆÓ ÂÓ‰ÂÈÎÙÈ΋ ‚Ï¿‚˘ Û οÔÈÔ fiÚÁ·ÓÔ ·Ú¿ ÙËÓ ·Ó›¯Ó¢ÛË Û ¯·ÌËÏ¿ ›‰· ¤ÎÊÚ·Û˘ ÏÔ˘ÛÈÊÂÚ¿Û˘ Û fiÚÁ·Ó· ̤۷ ÛÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÙˆÓ ‰‡Ô ÚÒÙˆÓ Â‚‰ÔÌ¿‰ˆÓ. ¢ÂÓ ·Ú·ÙËÚ‹ıËΠη̛· ¤Ó‰ÂÈÍË ÙÔÍÈÎfiÙËÙ·˜ ÛÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÙˆÓ 35 ËÌÂÚÒÓ Ô˘ ‰È‹ÚÎËÛÂ Ë ÌÂϤÙË. MÂÙ·ÊÂÚfiÌÂÓÔ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi T· ÁÔÓ›‰È· ÙˆÓ ÔÔ›ˆÓ ¤¯ÂÈ ÌÂÏÂÙËı› Ë ÌÂÙ·ÊÔÚ¿ Ì ÛÎÔfi ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Îˆ‰ÈÎÔÔÈÔ‡Ó ·˘ÍËÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜. ŒÚ¢Ó˜ ¿ÌÂÛ˘ ‹ ¤ÌÌÂÛ˘ ÌÂÙ·ÊÔÚ¿˜ ÙˆÓ ÁÔÓȉ›ˆÓ Ù˘ ÌÔÚÊÔÁÂÓÂÙÈ΋˜ ÚˆÙ½Ó˘ ÙÔ˘ ÔÛÙÔ‡-2 Î·È -7 (BMP-2 Î·È BMP-7, ·ÓÙ›ÛÙÔȯ·), ÙÔ˘ ‚·ÛÈÎÔ‡ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· ÙˆÓ ÈÓÔ‚Ï·ÛÙÒÓ (bFGF), Ù˘ ÔÛÙÂÔÚÔÙÂÁÂÚ›Ó˘ (OPG) Î·È ÙÔ˘ ÚÔÂÚ¯fiÌÂÓÔ˘ ·fi Ù· ·ÈÌÔÂÙ¿ÏÈ· ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·-B (PDGF-B), ̤ۈ ÈÒÓ ‹ Ï·ÛÌȉ›ˆÓ Û ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ ÂÈÚ·Ì·Ùfi˙ˆˆÓ ¤¯Ô˘Ó ·ÚÔ˘ÛÈ¿ÛÂÈ ÂÓı·ÚÚ˘ÓÙÈο ·ÔÙÂϤÛÌ·Ù· (¶›Ó. 3). ™Ù· Ï·›ÛÈ· Ù˘ ÚÔÛ¿ıÂÈ·˜ ·Ó¿Ï·Û˘ ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ È‰È·›ÙÂÚÔ ÂӉȷʤÚÔÓ ¤¯ÂÈ ÚÔÛÂÏ·ÛÂÈ Î·È Ë ÌÂÙ·ÊÔÚ¿ ÁÔÓȉ›ˆÓ Ô˘ ·ÔÛÎÔÔ‡Ó ÛÙË Ú‡ıÌÈÛË Ù˘ ·ÓÔÛÔÏÔÁÈ΋˜ ·¿ÓÙËÛ˘ ÙÔ˘ ÍÂÓÈÛÙ‹, Ì ÛÎÔfi ÙË ‚ÂÏÙÈÛÙÔÔ›ËÛË ÙˆÓ Û˘ÓıËÎÒÓ ÙÔ˘ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ. E›Ó·È ‰˘Ó·ÙfiÓ Ù· ·ÙÙ·Ú·-ÛÙfi¯ÔÈ Ó· ÙÚÔÔÔÈËıÔ‡Ó ÁÂÓÂÙÈο ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó ‰‡Ô ‹ ÂÚÈÛÛfiÙÂÚ· ÁÔÓ›‰È·. T· ÁÔÓ›‰È· ÌÔÚÔ‡Ó Ó· Â›Ó·È ·ÓÂÍ¿ÚÙËÙ·, ÔfiÙÂ Ë ·ÓÙÈÁÚ·Ê‹ ÙÔ˘˜ Ú˘ıÌ›˙ÂÙ·È ·fi ‰È·ÊÔÚÂÙÈÎÔ‡˜ ˘ÔÎÈÓËÙ¤˜. ™ÙËÓ ÂÚ›ÙˆÛË ·˘Ù‹, fï˜, ÌÔÚ› Ó· ˘¿ÚÍÂÈ ·ÓÙ·ÁˆÓÈÛÙÈ΋ ‰Ú¿ÛË ÌÂٷ͇ ÙˆÓ ‰È·ÊÔÚÂÙÈÎÒÓ ˘ÔÎÈÓËÙÒÓ. EÓ·ÏÏ·ÎÙÈο, Ù· ÁÔÓ›‰È· ÌÔÚÔ‡Ó Ó· Û˘Ó‰ÂıÔ‡Ó ÌÂٷ͇ ÙÔ˘˜ Ì ÂÛˆÙÂÚÈΤ˜ ·ÏÏËÏÔ˘¯›Â˜ RNA Û‡Ó‰ÂÛ˘ Ì ÚÈ‚ÔÛÒÌ·Ù· (internal ribosome entry site sequences, IRES sequences) Î·È Ë ÌÂÙ·ÁÚ·Ê‹ ÙÔ˘˜ Ó· Ú˘ıÌ›˙ÂÙ·È ·fi ÙÔÓ ›‰ÈÔ ˘ÔÎÈÓËÙ‹. T· ÁÔÓ›‰È· ÌÂÙ·ÁÚ¿ÊÔÓÙ·È ÛÙÔ ›‰ÈÔ mRNA ·ÏÏ¿ Û˘Ó‰¤ÔÓÙ·È ÛÙ· ÚÈ‚ÔÛÒÌ·Ù· ̤ۈ ÙˆÓ ·ÏÏËÏÔ˘¯ÈÒÓ IRES Î·È ÌÂÙ·ÊÚ¿˙ÔÓÙ·È ·ÓÂÍ¿ÚÙËÙ·. øÛÙfiÛÔ, ¤¯ÂÈ ·Ó·ÊÂÚı› ˆ˜ Ë ¤ÎÊÚ·ÛË ÙÔ˘ ‰Â‡ÙÂÚÔ˘ ÁÔÓȉ›Ô˘, Ô˘ ¤ÂÙ·È Ù˘ ·ÏÏËÏÔ˘¯›·˜ Û‡Ó‰ÂÛ˘ Ì ٷ ÚÈ‚ÔÛÒÌ·Ù· ‰ÂÓ ÍÂÂÚÓ¿ Û˘Ó‹ıˆ˜ ÙÔ 20-50% Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ ÚÒÙÔ˘ ÁÔÓȉ›Ô˘31. 60 Cirelli et al.45 administered intramuscularly adeno-associated viruses carrying TNFR- immunoglobulin Fc fusion gene in rats. After 4 weeks, the rats were subjected to induction of experimental periodontitis by intra-gingival application of Porphyromonas gingivalis lipopolysaccharide three times per week for 8 weeks. They studied three groups of rats: (1) rats to which virus application had preceded lipopolysaccharide administration (in order to induce periodontitis) (combination of virus application and lipopolysaccharide administration), (2) rats with no virus application prior to lipopolysaccharide administration (lipopolysaccharide administration only) and (3) rats which received only the adenovirus delivery vehicle (with no adenovirus) and they were not subjected to lipopolysaccharide administration (no periodontitis induction, control group). Inflammatory cell number in the alveolar bone and the subepithelial area at 4 weeks as well as inflammatory cell number in the subepithelial area at 8 weeks were statistically significantly lower in the group with combined virus application and lipopolysaccharide administration in comparison to the group with lipopolysaccharide administration. Moreover, in the group with combined virus application and lipopolysaccharide administration there was statistically significantly lower linear bone resorption by 61.2% and 48.5% at 4 and 8 weeks, respectively. The volumetric bone loss was reduced and the bone density was increased for the group with combined virus application and lipopolysaccharide administration. Comparison between the group of combined virus application and lipopolysaccharide administration and the group of lipopolysaccharide administration alone in terms of volumetric bone loss, revealed statistically significant difference at 8 weeks. For the group of combined virus application and lipopolysaccharide administration, there were statistically significantly lower osteoclast number, bone surface in contact to osteoclast cells (at 4 and 8 weeks), interleukin-6(IL-6), interleukin-10( IL-10), receptor activator of nuclear factor kappa-B ligand (RANKL) and OPG expression (at 4 weeks) in comparison to the group of lipopolysaccharide administration alone. Comparison between the group with the combination of virus application and lipopolysaccharide administration and the control group showed similar osteoclast number, IL-6, IL-10, RANKL, OPG, interleukin-1‚ (IL-1‚) and TNF-· expression levels for both groups. Furthermore, IL-1‚ and TNF-· expression levels were similar for all three groups45. At 24 and 48 hours, the group with lipopolysaccharide administration alone presented statistically significantly higher IL-1‚ and TNF-· expression in comparison to the control group. The group with the combination of virus application and lipopolysaccharide administration presented higher IL1‚ and TNF-· expression, which reached statistically significant levels at 48 hours. Though, they were statistically significantly lower as compared to the group with lipopolysaccharide administration alone. This indicates that the inhibitory effect of TNFR on the expression of these inflammatory mediators is more prominent in the Hellenic Stomatological Review 57: 39-71, 2013 Hellenic Stomatological Review 57: 39-71, 2013 In-vitro A‰ÂÓÔ˝Ô› E›Ì˘Â˜ MÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡-7, noggin (·ÓÙ·ÁˆÓÈÛÙ‹˜) BÏ¿‚˜ Ê·ÙÓÈ·ÎÔ‡ ÔÛÙÔ‡ οو ÁÓ¿ıÔ˘ In-vivo ¶Ï·ÛÌ›‰È· MÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡-2 ™Î‡ÏÔÈ XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ beagle ÂÚÈÔ‰ÔÓÙÈΤ˜ ‚Ï¿‚˜ Û¯‹Ì·ÙÔ˜ U ÛÙËÓ ·ÚÂȷ΋ ÂÈÊ¿ÓÂÈ· ÂÁÁ‡˜ ÚÈ˙ÒÓ Î¿Ùˆ ÚÔÁoÌÊ›ˆÓ ¢ÂÚÌ·ÙÈÎÔ› ÈÓÔ‚Ï¿ÛÙ˜ MÂÛÂÁ¯˘Ì·ÙÈο ‚Ï·ÛÙÔ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ In-vitro A‰ÂÓÔ˝Ô› MÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡-2 New XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ Zealand ÂÚÈÔ‰ÔÓÙÈΤ˜ Ï·ÁÔ› ‚Ï¿‚˜ K‡ÙÙ·Ú·ÛÙfi¯ÔÈ T¯ÓÈ΋ ºÔÚ¤·˜ ZÒÔ °ÔÓ›‰ÈÔ BÏ¿‚Ë ZÂÏ·Ù›ÓË - ¶ÏÔ˘ÚÔÓÈÎfi F127 M¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ - 8 ‚‰ÔÌ¿‰Â˜ - ¢È¿ÚÎÂÈ· 32 35 ¶Ï‹Ú˘ ÔÛÙÈ΋ ·Ó¿Ï·ÛË Î·È ‰ËÌÈÔ˘ÚÁ›· Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡ ÏÔ‡ÛÈÔ˘ Û ›Ó˜ Î·È ·ÁÁ›·. ™Ù·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙ½Ó˘, Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡ Î·È ÔÛÙÔ‡ Û ۇÁÎÚÈÛË Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ÌfiÓÔ ·Ï·ÙÔ‡¯Ô˘ ÔÚÔ‡, ·ÚfiÌÔÈ· Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ·ÓıÚÒÈÓ˘ ·Ó·Û˘Ó‰˘·Ṳ̂Ó˘ ÌÔÚÊÔÁÂÓÂÙÈ΋˜ ÚˆÙ½Ó˘ ÙÔ˘ ÔÛÙÔ‡-2 T·¯Â›· ÔÛÙÂÔÁ¤ÓÂÛË, ÔÛÙÂ˚ÓÔÁ¤ÓÂÛË Î·È ÚԂϤ„ÈÌË ·Ó¿Ï·ÛË ÙˆÓ ‚Ï·‚ÒÓ. AÓ·ÛÙÔÏ‹ Ù˘ ÔÛÙÂÔÁ¤ÓÂÛ˘ ·fi ·ÙÙ·Ú· ÂÎÊÚ¿˙ÔÓÙ· noggin. 34 MÂϤÙË ¢ËÌÈÔ˘ÚÁ›· ÔÛÙ½Ó˘ Î·È ÈÓÒÓ ÙÔ˘ Sharpey. ™Ù·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡ Û ۇÁÎÚÈÛË Ì ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌË ÁÂÓÂÙÈο ÙÚÔÔÔÈËÌ¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ Î·È ÂÊ·ÚÌÔÁ‹ ÌfiÓÔ ÙÔ˘ ̤ÛÔ˘. AÔÙÂϤÛÌ·Ù· ¶›Ó·Î·˜ 3. MÂϤÙ˜ ÌÂÙ·ÊÔÚ¿˜ ÁÔÓȉ›ˆÓ ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ Î·È ÂÚÈÂÌÊ˘ÙÂ˘Ì·ÙÈÎÒÓ ÈÛÙÒÓ Û ÂÈÚ·Ì·Ùfi˙ˆ·. μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review 61 62 ™Î‡ÏÔÈ beagle ¶ÂÚÈÂÊ˘ÙÂ˘Ì·ÙÈΤ˜ ‚Ï¿‚˜ οو ÁÓ¿ıÔ˘ - ™Î‡ÏÔÈ XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ Beagle ‚Ï¿‚˜ ÂÚÈÔ¯‹˜ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÚÈ˙ÒÓ Î·ÙËÁÔÚ›·˜ II BÏ¿‚˜ Ù˘ ÂÚÈÔ¯‹˜ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÚÈ˙ÒÓ In-vitro In-vivo - A‰ÂÓÔ˚Ô› MÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡-7 MÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡-7 In-vitro E˘Î·ÚȈÙÈÎfi Ï·ÛÌ›‰ÈÔ pDC316 B·ÛÈÎfi˜ ·˘ÍËÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÙˆÓ ÈÓÔ‚Ï·ÛÙÒÓ Î·È Ú¿ÛÈÓË ÊıÔÚ›˙Ô˘Û· ÚˆÙ½ÓË MÂÌ‚Ú¿ÓË ÎÔÏÏ·ÁfiÓÔ˘ ™Ùڈ̷ÙÈο ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ KÈÙÔ˙¿ÓË/ KÔÏÏ·ÁfiÓÔ/ ·ÙÙ·Ú· ÂÚÈÚÚÈ˙›Ô˘ - MÂÛÂÁ¯˘Ì·ÙÈο ÛÙڈ̷ÙÈο ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ MÂÁ·Ï‡ÙÂÚË ‰Ú·ÛÙËÚÈfiÙËÙ· ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘, ¤ÎÊÚ·ÛË ÔÛÙÂÔÔÓÙ›Ó˘ Î·È ÛÈ·ÏÔÚˆÙ½Ó˘ ·fi Ù· ·ÙÙ·Ú· ÙÔ˘ ̤ÛÔ˘ ÚÈÓ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙÔ˘ Î·È ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡ 4 Î·È 8 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿, Û ۇÁÎÚÈÛË Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ÙÔ˘ ̤ÛÔ˘ ¯ˆÚ›˜ ·‰ÂÓÔ˚Ô‡˜ ʤÚÔÓÙ˜ ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ÌÔÚÊÔÁÂÓÂÙÈ΋˜ ÚˆÙ½Ó˘ ÙÔ˘ ÔÛÙÔ‡-7. 38 37 ™Ù·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ÂÚÈÔ¯‹ ÓÂÔ‰ËÌÈÔ˘ÚÁËı¤ÓÙÔ˜ ÔÛÙÔ‡ Î·È Ì‹ÎÔ˜ ÓÂÔ‰ËÌÈÔ˘ÚÁËı›۷˜ ÔÛÙ½Ó˘ Û ۇÁÎÚÈÛË Ì ÙË ÌË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î˘ÙÙ¿ÚˆÓ Î·È ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌË ÁÂÓÂÙÈο ÙÚÔÔÔÈËÌ¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ, Ù· ÔÔ›· ·ÚÔ˘Û›·Û·Ó ›Û˘ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ Û ۇÁÎÚÈÛË Ì ÙË ÌË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î˘ÙÙ¿ÚˆÓ. 12 ‚‰ÔÌ¿‰Â˜ 3 Ì‹Ó˜ 36 ™Ù·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË Ù·¯‡ÙËÙ· ·Ó¿Ï·Û˘ ÙÔ˘ ÔÛÙÔ‡ Û ۇÁÎÚÈÛË Ì ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌË ÁÂÓÂÙÈο ÙÚÔÔÔÈËÌ¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ 6 ‚‰ÔÌ¿‰Â˜ μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review Hellenic Stomatological Review 57: 39-71, 2013 In-vivo In-vitro A‰ÂÓÔ˚Ô› ÛÂ Û˘ÁΤÓÙÚˆÛË 5.5x108 ‹ 5.5x109 pfu/ml A‰ÂÓÔ˚Ô› AÏ˘Û›‰· B ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ MÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡-2 ¶ÂÚÈÂÌÊ˘Ù¢- E›Ì˘Â˜ Ì·ÙÈΤ˜ ‚Ï¿‚˜, ¯ÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ Ù·˘Ùfi¯ÚÔÓ· Ì ÚÔÂÙÔÈÌ·Û›· ÙÔ˘ ÔÛÙÔ‡ ÁÈ· ÙÔÔı¤ÙËÛË ÂÌÊ˘ÙÂ˘Ì¿ÙˆÓ ™Î‡ÏÔÈ ¶ÂÚÈÔ‰ÔÓÙÈbeagle Τ˜ ‚Ï¿‚˜ ÁÔÌÊ›ˆÓ οو ÁÓ¿ıÔ˘ In-vitro ¶Ï·ÛÌ›‰ÈÔ OÛÙÂÔÚÔÙÂÁÂÚ›ÓË ™Î‡ÏÔÈ XÂÈÚÔ˘ÚÁÈο ÚÔÎÏËı›Û˜ ÔÚÈ˙fiÓÙȘ ÔÛÙÈΤ˜ ‚Ï¿‚˜ 4x4x3mm ÛÙËÓ ·ÚÂȷ΋ ÂÈÊ¿ÓÂÈ· ÚÔÁÔÌÊ›ˆÓ A‰È·ÊÔÚÔÔ›ËÙ· ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú· ™Ùڈ̷ÙÈο ·ÙÙ·Ú· Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ Hellenic Stomatological Review 57: 39-71, 2013 - M‹ÙÚ· ÎÔÏÏ·ÁfiÓÔ˘ PLGA 8 ‚‰ÔÌ¿‰Â˜ - 6 ‚‰ÔÌ¿‰Â˜ ¢ËÌÈÔ˘ÚÁ›· ÔÛÙ½Ó˘ Î·È ÈÓÒÓ ÙÔ˘ Sharpey ÛÙȘ ·ÔÁ˘Ìӈ̤Ó˜ ·fi ÔÛÙ½ÓË ÚÈ˙ÈΤ˜ ÂÈÊ¿ÓÂȘ, Û ·ÓÙ›ıÂÛË Ì ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌË ÁÂÓÂÙÈο ÙÚÔÔÔÈËÌ¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ, fiÔ˘ ·Ú·ÙËÚ‹ıËΠ·ÙÂÏ‹˜ ÂԇψÛË Î·È ÂÓÙÔÈṲ̂ӷ ·ÔÚÚfiÊËÛË Ú›˙·˜. ™Ù·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙÔ‡ ÛÙȘ 8 ‚‰ÔÌ¿‰Â˜. EÈÙ¿¯˘ÓÛË Ù˘ ÔÛÙÈ΋˜ ·Ó¿Ï·Û˘ Û ۇÁÎÚÈÛË Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË Î˘ÙÙ¿ÚˆÓ ÊÂÚfiÓÙˆÓ ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ÏÔ˘ÛÈÊÂÚ¿Û˘, ·ÚfiÌÔÈ· Ì ÙËÓ ¯ÔÚ‹ÁËÛË ·Ó·Û˘Ó‰˘·Ṳ̂ÓÔ˘ ·ÓıÚÒÈÓÔ˘ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ BB. H ·˘ÍË̤ÓË Û˘ÁΤÓÙÚˆÛË ·‰ÂÓÔÈÒÓ ‹Ù·Ó ÂÚÈÛÛfiÙÂÚÔ ·ÔÙÂÏÂÛÌ·ÙÈ΋. ™Ù·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ‰ËÌÈÔ˘ÚÁ›· ÔÛÙ½Ó˘, Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡ Î·È ÔÛÙÔ‡ Û ۇÁÎÚÈÛË Ì ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌË ÁÂÓÂÙÈο ÙÚÔÔÔÈËÌ¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ, ÙËÓ ÂÊ·ÚÌÔÁ‹ ÌfiÓÔ ÙÔ˘ ̤ÛÔ˘ Î·È ÌfiÓÔ ÙËÓ ÚÈ˙È΋ ·fiÍÂÛË. 41 40 39 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review 63 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review MÔÚÊÔÁÂÓÂÙÈΤ˜ ÚˆÙ½Ó˜ ÙÔ˘ ÔÛÙÔ‡ (BMPs) Œ¯ÂÈ ‰Âȯı› fiÙÈ ·Ú·ÙÂٷ̤ÓË ¤ÎıÂÛË Û ¯·ÌËÏ‹ Û˘ÁΤÓÙÚˆÛË ·Ó·Û˘Ó‰˘·Ṳ̂Ó˘ ·ÓıÚÒÈÓ˘ ÌÔÚÊÔÁÂÓÂÙÈ΋˜ ÚˆÙ½Ó˘ ÙÔ˘ ÔÛÙÔ‡-2 ÚÔ¿ÁÂÈ ÙËÓ ÔÛÙÂ˚ÓÔÁ¤ÓÂÛË. øÛÙfiÛÔ, ÙÔ Úfi‚ÏËÌ· ÙÔ˘ ÌÈÎÚÔ‡ ¯ÚfiÓÔ˘ ËÌ›ÛÂÈ·˜ ˙ˆ‹˜ Ù˘ fiÙ·Ó ¯ÔÚËÁÂ›Ù·È ÙÔÈο ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ ‚Ï¿‚˘ ηıÈÛÙ¿ ··Ú·›ÙËÙË ÙË ¯ÔÚ‹ÁËÛË ˘„ËÏÒÓ ‰fiÛˆÓ. Y„ËϤ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ, fï˜, ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛÙ› Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ÙÔÈÎÒÓ ÂÈÏÔÎÒÓ, fiˆ˜ ·Á·ψÛË Î·È ÔÛÙÈ΋ ·ÔÚÚfiÊËÛË. H ·Ú·ÙÂٷ̤ÓË ·ÂÏ¢ı¤ÚˆÛË ·fi ·ÙÙ·Ú· Ô˘ ¤¯Ô˘Ó ÙÚÔÔÔÈËı› ÁÂÓÂÙÈο ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó ÌÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡2 ¤¯ÂÈ ‰Âȯı› fiÙÈ ÌÔÚ› Ó· ηٷÛÙ‹ÛÂÈ ‰˘Ó·Ù‹ ÙË Ì›ˆÛË Ù˘ ··ÈÙÔ‡ÌÂÓ˘ Û˘ÁΤÓÙÚˆÛ‹˜ Ù˘ ηٿ ÂÚ›Ô˘ 1.000 ÊÔÚ¤˜32, 41. OÈ Yang Î·È Û˘Ó.31 ‰È·›ÛÙˆÛ·Ó fiÙÈ ·ÓıÚÒÈÓ· ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÚÚÈ˙›Ô˘ Ô˘ ›¯·Ó ÙÚÔÔÔÈËı› ÁÂÓÂÙÈο ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó ÌÔÚÊÔÁÂÓÂÙÈ΋ ÚˆÙ½ÓË ÙÔ˘ ÔÛÙÔ‡-7 (BMP-7) Î·È ÚÔÛÔÌÔÈ¿˙ÔÓÙ· Ì ÈÓÛÔ˘Ï›ÓË ·˘ÍËÙÈÎfi ·Ú¿ÁÔÓÙ·-1 (IGF-1) ‹ ÌfiÓÔ BMP-7, ÌÂÙ¿ ·fi 3 Ë̤Ú˜ ·ÚÔ˘Û›·Û·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ¤ÎÊÚ·ÛË BMP-7, ‰Ú·ÛÙËÚÈfiÙËÙ· ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘ Î·È ¤ÎÊÚ·ÛË ÎÔÏÏ·ÁfiÓÔ˘ Ù‡Ô˘ I, Runx2 Î·È ÛÈ·ÏÔÚˆÙ½Ó˘ ÙÔ˘ ÔÛÙÔ‡ Û ۯ¤ÛË Ì ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÚÚÈ˙›Ô˘ ÁÂÓÂÙÈο ÙÚÔÔÔÈË̤ӷ ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó Ú¿ÛÈÓË ÊıÔÚ›˙Ô˘Û· ÚˆÙ½ÓË Î·È ÌË ÁÂÓÂÙÈο ÙÚÔÔÔÈË̤ӷ ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÚÚÈ˙›Ô˘. T· ·ÙÙ·Ú· Ô˘ ›¯·Ó ÙÚÔÔÔÈËı› ÁÂÓÂÙÈο ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó BMP-7 Î·È IGF-1 ·ÚÔ˘Û›·Û·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ‰Ú·ÛÙËÚÈfiÙËÙ· ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘ Î·È ¤ÎÊÚ·ÛË ÎÔÏÏ·ÁfiÓÔ˘ Ù‡Ô˘ I Î·È Runx2 Û ۯ¤ÛË Ì ٷ ·ÙÙ·Ú· Ô˘ ›¯·Ó ÙÚÔÔÔÈËı› ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó ÌfiÓÔ BMP-7. H ̤ÁÈÛÙË ¤ÎÊÚ·ÛË BMP-7 Î·È ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ ΢ÙÙ¿ÚˆÓ ·Ú·ÙËÚ‹ıËΠ9 Ë̤Ú˜ ÌÂÙ¿, ÂÓÒ Ë ¤ÎÊÚ·Û‹ ÙÔ˘˜ ·Ú¤ÌÂÈÓ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÙˆÓ ÁÂÓÂÙÈο ÙÚÔÔÔÈËÌ¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó Ú¿ÛÈÓË ÊıÔÚ›˙Ô˘Û· ÚˆÙ½ÓË Î·È Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÙˆÓ ÌË ÁÂÓÂÙÈο ÙÚÔÔÔÈËÌ¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ Ì¤¯ÚÈ Î·È ÙȘ 27 Ë̤Ú˜31. A˘ÍËÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÚÔÂÚ¯fiÌÂÓÔ˜ ·fi Ù· ·ÈÌÔÂÙ¿ÏÈ· (PDGF) O ÚÔÂÚ¯fiÌÂÓÔ˜ ·fi Ù· ·ÈÌÔÂÙ¿ÏÈ· ·˘ÍËÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜-AA (PDGF-AA), Ô˘ ·ÔÙÂÏÂ›Ù·È ·fi ‰‡Ô ·Ï˘Û›‰Â˜ A ÙÔ˘ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· ÙÔ˘ ÚÔÂÚ¯fiÌÂÓÔ˘ ·fi Ù· ·ÈÌÔÂÙ¿ÏÈ· (PDGF), Û˘Ó‰ÂfiÌÂÓÔ˜ ÛÙÔÓ ˘Ô‰Ô¯¤· · ÙÔ˘ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ, Ô˘ Â›Ó·È ˘Ô‰Ô¯¤·˜ Ù˘ÚÔÛÈÓÈ΋˜ ÎÈÓ¿Û˘, ¿ÁÂÈ ÙË ÊˆÛÊÔÚ˘Ï›ˆÛ‹ ÙÔ˘ Ë ÔÔ›· ˘ÚÔ‰ÔÙ› ¤Ó· ηٷÚÚ¿ÎÙË ÂÓ‰Ô΢ÙÙ·ÚÈÎÒÓ Î·È ÂÍˆÎ˘ÙÙ·ÚÈÎÒÓ ÛËÌ¿ÙˆÓ. OÈ Chen Î·È Giannobile42 ÌÂÙ¿ ·fi ÚÔÛ‚ÔÏ‹ ‰ÂÚÌ·ÙÈÎÒÓ ÈÓÔ‚Ï·ÛÙÒÓ Â›Ì˘ˆÓ Ì ·‰ÂÓÔ˚Ô‡˜ Ô˘ ¤ÊÂÚ·Ó ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ·Ï˘Û›‰·˜ A ·Ú·Ù‹ÚËÛ·Ó ÊˆÛÊÔÚ˘Ï›ˆÛË ÙÔ˘ ˘Ô‰Ô¯¤· · ÛÙȘ 8 ÒÚ˜ Î·È ·‡ÍËÛ‹ Ù˘ ̤¯ÚÈ Î·È ÙȘ 96 ÒÚ˜, ÔfiÙÂ Î·È Û˘ÏϤ¯ıËÎ·Ó Ù· ÙÂÏÂ˘Ù·›· ·ÙÙ·Ú· Ô˘ ÌÂÏÂÙ‹ıËηÓ. AÓÙ›ÛÙÔÈ¯Ë ÌÂÙ·‚ÔÏ‹ ÙˆÓ ÂȤ‰ˆÓ ʈÛÊÔÚ˘Ï›ˆÛ˘ ·ÚÔ˘Û›·Û·Ó ÔÈ ERK1/2 Î·È Akt, ÔÈ ÔÔ›ÔÈ ÂÌϤ64 short term. This may be due to the reduction of the lipopolysaccharide-enhanced expression of the inflammatory mediators with time, due to the development of resistance to endotoxins in an attempt of the host to regulate the local immune reaction45. Other gene transferring means It has been suggested that among the non-viral vectors plasmids can be used for genetic material transfer in gene therapy for periodontal tissue regeneration. Chen et al.46 studied the luciferase expression after transferring recombinant plasmids containing luciferase gene to rat periodontal tissues by using nanobubbles and ultrasound waves (pulse 10Ìs and energy 36J/cm2). Transferring recombinant plasmids containing luciferase gene by using nanobubbles and ultrasound waves led to statistically significantly higher luciferase expression on day 1 as compared to plasmids alone, plasmids mixed with nanobubbles as well as to plasmids followed by ultrasound waves. However, on day 3 luciferase expression returned to the initial levels. It was claimed that the collapse of nanobubbles and cavitation bubbles by the ultrasound waves caused a transient increase in cell permeability leaving plasmids to enter into them. Ultrasound waves should be of a short duration, since longlasting waves result in a non-reversible increase in cell permeability, and they of low energy, since high energy results in reduction of their vitality. The short-term expression of genes transferred in such way that make repeating treatment necessary for the maintenance of high gene expression levels, might be attributed to the rapid plasmid degradation due to the high blood circulation in the area. Optimizing ultrasound wave parameters and developing an ultrasound wave production device specifically for this purpose might increase the gene expression time46. CONCLUSION Successful periodontal tissue regeneration is based on the presence of cells, cellular signals regulating cellular activity, scaffolds supporting periodontal regeneration, vascularization, where cellular signals are involved, and microbial control. Mesenchymal stem cell transplantation for periodontal tissue regeneration by providing new cells, which proliferate, differentiate, secret cellular signals and help in tissue growth and differentiation, has showed encouraging results in periodontal regeneration, mainly in a pre-clinical level. Moreover, it is being studied in clinical trials. Gene transfer has demonstrated promising pre-clinical results in periodontal regeneration, which offers the possibility to express cellular signals by target-cells aiming at the induction of tissue growth and differentiation or the control of the host immune response to microbial stimuli. Mesenchymal stem cell transplantation and gene transfer, either alone or combined, might prove to offer further benefit to periodontal tissue regeneration, which is currently explored. Hellenic Stomatological Review 57: 39-71, 2013 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ÎÔÓÙ·È ÛÙÔÓ Î·Ù·ÚÚ¿ÎÙË ÛËÌ¿ÙˆÓ Ô˘ ˘ÚÔ‰ÔÙ› Ë ÊˆÛÊÔÚ˘Ï›ˆÛË ÙÔ˘ ˘Ô‰Ô¯¤· ·. MÂÙ¿ ·fi ¯ÔÚ‹ÁËÛË ·Ó·Û˘Ó‰˘·Ṳ̂ÓÔ˘ ·ÓıÚÒÈÓÔ˘ PDGF-AA, Ë ÊˆÛÊÔÚ˘Ï›ˆÛË ÙÔ˘ ˘Ô‰Ô¯¤· · ‰È·ÙËÚ‹ıËΠ̤¯ÚÈ ÙȘ 48 ÒÚ˜, ·ÏÏ¿ ÛÙȘ 72 ÒÚ˜ ›¯Â ·Ú¯›ÛÂÈ Ó· ÂÍ·ÛıÂÓ›. AÓÙ›ÛÙÔȯ·, ʈÛÊÔÚ˘Ï›ˆÛË ÙˆÓ ERK1/2 Î·È Akt ·Ú·ÙËÚ‹ıËΠÛÙȘ 8 ÒÚ˜ Î·È ‰È·ÙËÚ‹ıËΠ·ÓÙ›ÛÙÔȯ· ̤¯ÚÈ ÙȘ 72 Î·È 48 ÒÚ˜. H ηı˘ÛÙÂÚË̤ÓË ÊˆÛÊÔÚ˘Ï›ˆÛË ÙÔ˘ ˘Ô‰Ô¯¤· Ô˘ ·Ú·ÙËÚ‹ıËΠÌÂÙ¿ ·fi ÙË ÌfiÏ˘ÓÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ì ÙÔ˘˜ ÈÔ‡˜ ˘ÔÛÙËÚ›¯ıËΠfiÙÈ ÔÊ›ÏÂÙ·È ÛÙÔ ¯ÚfiÓÔ Ô˘ ··ÈÙÂ›Ù·È ÁÈ· ÙË ÌÂÙ·ÊÔÚ¿ Î·È ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘42. OÈ Lin Î·È Û˘Ó.43 ÌÂÙ¿ ·fi ÌfiÏ˘ÓÛË ·ÓıÚÒÈÓˆÓ Ô˘ÏÈÎÒÓ ÈÓÔ‚Ï·ÛÙÒÓ Ì ·‰ÂÓÔ˚Ô‡˜ Ô˘ ¤ÊÂÚ·Ó ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ·Ï˘Û›‰·˜ B ÙÔ˘ PDGF ·Ú·Ù‹ÚËÛ·Ó ¤ÎÊÚ·ÛË ÙÔ˘ ÚÔÂÚ¯fiÌÂÓÔ˘ ·fi Ù· ·ÈÌÔÂÙ¿ÏÈ· ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·-BB (PDGF-BB) ÛÙȘ 6 ÒÚ˜, Ë ÔÔ›· ‰È·ÙËÚ‹ıËΠÙÔ˘Ï¿¯ÈÛÙÔÓ Ì¤¯ÚÈ ÙȘ 96 ÒÚ˜. Œ¯ÂÈ ·Ó·ÊÂÚı› ˆ˜, Û ·ÓÙ›ıÂÛË Ì ÙËÓ ¿ÌÂÛË ·ÏÏ¿ ÌÈÎÚ‹˜ ‰È¿ÚÎÂÈ·˜ ‰Ú¿ÛË (Ï›ÁˆÓ ËÌÂÚÒÓ) ÙÔ˘ ÙÔÈο ÂÊ·ÚÌÔ˙fiÌÂÓÔ˘ ·Ó·Û˘Ó‰˘·Ṳ̂ÓÔ˘ PDGF-BB, ÌfiÏ˘ÓÛË Î˘ÙÙ¿ÚˆÓ Ì ·‰ÂÓÔ˚Ô‡˜ Ô˘ ʤÚÔ˘Ó ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ·Ï˘Û›‰·˜ B ÙÔ˘ PDGF ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ηı˘ÛÙÂÚË̤ÓË ·ÏÏ¿ ·Ú·ÙÂٷ̤ÓË ¤ÎÊÚ·Û‹ ÙÔ˘, Ô˘ ÌÂÈÔ‡ÌÂÓË ÛÙ·‰È·Î¿, ÙËÓ 14Ë Ë̤ڷ ÊÙ¿ÓÂÈ ÛÙÔ 20% ÙÔ˘ ˘„ËÏfiÙÂÚÔ˘ ÂȤ‰Ô˘ Ù˘40. ™Â ÌÂϤÙË ÙˆÓ Giannobile Î·È Û˘Ó.44 ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ Ô˘ ÌÔχÓıËÎ·Ó Ì ÈÔ‡˜ Ô˘ ¤ÊÂÚ·Ó ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ·Ï˘Û›‰·˜ A ÙÔ˘ PDGF ·ÚÔ˘Û›·Û·Ó ¤ÎÊÚ·Û‹ ÙÔ˘ ÌÂÙ¿ ·fi 24 ÒÚ˜ Ô˘ ‰È·ÙËÚ‹ıËΠ̤¯ÚÈ Î·È ÙȘ 7 Ë̤Ú˜, ÔfiÙÂ Û˘ÏϤ¯ıËÎ·Ó Ù· ÙÂÏÂ˘Ù·›· ·ÙÙ·Ú· Ô˘ ÌÂÏÂÙ‹ıËηÓ. MÂÙ¿ ·fi 24 ÒÚ˜, ÔÈ ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ Ô˘ ÌÔχÓıËÎ·Ó Ì ÈÔ‡˜ Ô˘ ¤ÊÂÚ·Ó ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ·Ï˘Û›‰·˜ A ÙÔ˘ PDGF ·ÚÔ˘Û›·Û·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË Û‡ÓıÂÛË DNA Î·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚË ‰Ú·ÛÙËÚÈfiÙËÙ· ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘ Û ۇÁÎÚÈÛË Ì ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ ÁÂÓÂÙÈο ÙÚÔÔÔÈË̤ÓÔ˘˜ ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó Ú¿ÛÈÓË ÊıÔÚ›˙Ô˘Û· ÚˆÙ½ÓË. H Û‡ÓıÂÛË DNA Î·È Ô ÔÏÏ·Ï·ÛÈ·ÛÌfi˜ ‹Ù·Ó Û ·ÚfiÌÔÈ· ›‰· ÌÂٷ͇ ÔÛÙÂ˚ÓÔ‚Ï·ÛÙÒÓ Ô˘ ÌÔχÓıËÎ·Ó Ì ÈÔ‡˜ Ô˘ ¤ÊÂÚ·Ó ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ·Ï˘Û›‰·˜ A ÙÔ˘ PDGF Î·È ÔÛÙÂ˚ÓÔ‚Ï·ÛÙÒÓ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ÁÈÓfiÙ·Ó Û˘Ó¯‹˜ ÂÊ·ÚÌÔÊ‹ PDGF. TËÓ 4Ë Î·È ÙËÓ 7Ë Ë̤ڷ ÔÈ ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ ÔÈ Ôԛ˜ ›¯·Ó ÙÚÔÔÔÈËı› ÁÂÓÂÙÈο ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó PDGF Î·È ÔÈ ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ ÛÙȘ Ôԛ˜ ÚÔÛÙ¤ıËΠPDGF ·ÚÔ˘Û›·Û·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ·‡ÍËÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙÔ˘˜ Û ۇÁÎÚÈÛË Ì ÙȘ ÔÛÙÂ˚ÓÔ‚Ï¿ÛÙ˜ ÔÈ Ôԛ˜ ›¯·Ó ÙÚÔÔÔÈËı› ÁÂÓÂÙÈο ÒÛÙ ӷ ÂÎÊÚ¿˙Ô˘Ó Ú¿ÛÈÓË ÊıÔÚ›˙Ô˘Û· ÚˆÙ½ÓË. øÛÙfiÛÔ, ÔÈ ÚÒÙ˜ ·ÚÔ˘Û›·˙·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ·‡ÍËÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙÔ˘˜ Û ۇÁÎÚÈÛË Ì ÙȘ ‰Â‡ÙÂÚ˜. EÔ̤ӈ˜, Ë ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘ ¤ÎıÂÛ˘ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÛÙÔÓ PDGF Ê·›ÓÂÙ·È Ó· ÂËÚ¿˙ÂÈ ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ. Œ¯ÂÈ ·Ó·ÊÂÚı› fiÙÈ Ë ÂÊ·ÚÌÔÁ‹ ·Ó·Û˘Ó‰˘·Ṳ̂ÓÔ˘ PDGF ÂӉ›ÎÓ˘Ù·È Û ‚Ï¿‚˜ fiÔ˘ Â›Ó·È È‰È·›ÙÂÚ· ÛËÌ·ÓÙÈ΋ Ë Ù·¯Â›· ¤Ó·ÚÍË ÙˆÓ ‰ÈÂÚÁ·ÛÈÒÓ Ù˘ ·Ó¿Ï·Û˘, ηıÒ˜ Ô ÌÈÎÚfi˜ ¯ÚfiÓÔ˜ ËÌ›ÛÂÈ·˜ ˙ˆ‹˜ Ô˘ ·ÚÔ˘ÛÈ¿˙ÂÈ ÌÂÙ¿ ÙËÓ ÙÔÈ΋ ÂÊ·ÚÌÔÁ‹ ÙÔ˘, ¿ÁÂÈ ÔÏÏ·Ï·ÛÈ·ÛÌfi Î·È ¯ËÌÂÈÔÙ·ÎÙÈ΋ ÚÔÛÎfiÏÏËÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ ¯ˆÚ›˜ Ó· Hellenic Stomatological Review 57: 39-71, 2013 REFERENCES 1. Pepelassi E, Xynogala I: Current status of regenerative techniques. Odontostomatological progress 2008; 63 (1): 126-145. 2. Pepelassi E: Regenerative techniques. In: Mantzavinos ZS, Vrotsos IA. Clinical Periodontology. 1st ed. Athens. Litsas Publ. 2002: 441-474. 3. Rios H, Lin Z, Oh B, Park CH, Giannobile WV: Cell- and genebased therapeutic strategies for periodontal regenerative medicine. J Periodontol 2011; 82: 1223-37. 4. McAllister BS: Stem cell-containing allograft matrix enhances periodontal regeneration: case presentations. Int J Periodontics Restorative Dent: 2011; 31 (2): 149-55. 5. 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Int J Periodontics Restorative Dent 2011; 31 (6): e94-e101. 14. Liu HC, E LL, Wang DS, Su F, Wu X, Shi ZP et al: Reconstruction of alveolar bone defects using bone morphogenetic protein 2 mediated rabbit dental pulp stem cells seeded on nano-hydroxyapatite/collagen/poly(L-lactide). Tissue Eng Part A 2011; 17 (19-20): 2417-33. 15. Park J-C, Kim J-M, Jung I-H, Kim JC, Choi S-H, Cho K-S et al: Isolation and characterization of human periodontal ligament (PDL) stem cells (PDLSCs) from the inflamed PDL tissue: in vitro and in vivo evaluations. J Clin Periodontol 2011; 38 (8): 721-31. 16. Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM et al: Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells 2008; 26 (4): 1065-73. 65 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ηı˘ÛÙÂÚ› ÛËÌ·ÓÙÈο ÙËÓ ¤Ó·ÚÍË Ù˘ ‰È·ÊÔÚÔÔ›ËÛ‹˜ ÙÔ˘˜. AÓÙ›ıÂÙ·, Ë ¯ÔÚ‹ÁËÛË ·‰ÂÓÔ˚ÒÓ Ô˘ ʤÚÔ˘Ó ÙÔ ÁÔÓ›‰ÈÔ ·Ï˘Û›‰ˆÓ ÙÔ˘ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· ÙÔ˘ ÚÔÂÚ¯fiÌÂÓÔ˘ ·fi Ù· ·ÈÌÔÂÙ¿ÏÈ· ›Ûˆ˜ Ó· ÂӉ›ÎÓ˘Ù·È ÂÚÈÛÛfiÙÂÚÔ Û ÌÂÁ·Ï‡ÙÂÚ˜ ‚Ï¿‚˜, fiÔ˘ Ë ·Ú·ÙÂٷ̤ÓË ‰Ú¿ÛË ÙÔ˘ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· ÙÔ˘ ÚÔÂÚ¯fiÌÂÓÔ˘ ·fi Ù· ·ÈÌÔÂÙ¿ÏÈ· ı· ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ·Ú·ÁˆÁ‹ ÌÂÁ·Ï‡ÙÂÚÔ˘ ·ÚÈıÌÔ‡ ΢ÙÙ¿ÚˆÓ Î·ı˘ÛÙÂÚÒÓÙ·˜, fï˜, ÂÚÈÛÛfiÙÂÚÔ ÙËÓ ¤Ó·ÚÍË Ù˘ ‰È·ÊÔÚÔÔ›ËÛ‹˜ ÙÔ˘˜, Ô˘ ·ÎÔÏÔ˘ı› ÙËÓ ÂÍ·Ûı¤ÓËÛË Ù˘ ‰Ú¿Û˘ ÙÔ˘40. P‡ıÌÈÛË Ù˘ ·ÓÔÛÔÏÔÁÈ΋˜ ·¿ÓÙËÛ˘ ÙÔ˘ ÍÂÓÈÛÙ‹ YÔ‰Ô¯¤·˜ ÙÔ˘ ·Ú¿ÁÔÓÙ· Ó¤ÎÚˆÛ˘ ÙˆÓ fiÁÎˆÓ (TNFR) O ·Ú¿ÁÔÓÙ·˜ Ó¤ÎÚˆÛ˘ ÙˆÓ fiÁΈÓ-· (TNF-·) ÚÔ¿ÁÂÈ ÙËÓ ÔÛÙÈ΋ ·ÔÚÚfiÊËÛË ‰ÈÂÁ›ÚÔÓÙ·˜ ÙË ‰È·ÊÔÚÔÔ›ËÛË Î·È ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ÔÛÙÂÔÎÏ·ÛÙÒÓ. O TNF Û˘Ó‰¤ÂÙ·È Ì ‰‡Ô ˘Ô‰Ô¯Â›˜, ÙÔÓ p55 Î·È p75 ˘Ô‰Ô¯¤·. £Âڷ›˜ ·ÓÔÛÔÏÔÁÈ΋˜ Ú‡ıÌÈÛ˘ Ô˘ ¤¯Ô˘Ó ˆ˜ ‚¿ÛË ÙË ‰¤ÛÌ¢ÛË ÙÔ˘ TNF ¤¯Ô˘Ó ÂÊ·ÚÌÔÛÙ› ÂÈÙ˘¯Ò˜ Û ·ÓıÚÒÔ˘˜ ÁÈ· ÙË ıÂڷ›· Ù˘ ÚÂ˘Ì·ÙÔÂȉԇ˜ ·ÚıÚ›Ùȉ·˜. T· Ê¿Ú̷η Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Â›ÙÂ Â›Ó·È ÌÔÓÔÎψÓÈο ·ÓÙÈÛÒÌ·Ù· ÙÔ˘ TNF ›Ù ڈÙ½Ó˜ Ô˘ ÂÚȤ¯Ô˘Ó ÙÔÓ p75 ˘Ô‰Ô¯¤· ÙÔ˘ TNF Û˘ÓÙËÁ̤Ó˜ Ì ÙÔ Fc ÙÌ‹Ì· ·ÓıÚÒÈÓ˘ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ IgG145. OÈ Cirelli Î·È Û˘Ó.45 ¯ÔÚ‹ÁËÛ·Ó ÂÓ‰ÔÌ˘˚ο ÈÔ‡˜ Û¯ÂÙÈ˙fiÌÂÓÔ˘˜ Ì ·‰ÂÓÔ˚Ô‡˜ Ô˘ ¤ÊÂÚ·Ó ÙÔ ÁÔÓ›‰ÈÔ ÙÔ˘ ˘Ô‰Ô¯¤· ÙÔ˘ TNF Û˘ÓÙËÁ̤ÓÔ˘ Ì ÙÔ ÙÌ‹Ì· Fc ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ ÛÂ Â›Ì˘Â˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ÌÂÙ¿ ·fi 4 ‚‰ÔÌ¿‰Â˜ ÚÔÎÏ‹ıËΠÂÚÈÔ‰ÔÓÙ›Ùȉ· Ì ÙÔÈ΋ ÂÊ·ÚÌÔÁ‹ ÛÙ· ԇϷ ÏÈÔÔÏ˘Û·Î¯·ÚÈÙÒÓ ÙÔ˘ ÌÈÎÚÔ‚È·ÎÔ‡ ÛÙÂϤ¯Ô˘˜ Porphyromonas gingivalis, ÙÚÂȘ ÊÔÚ¤˜ ‚‰ÔÌ·‰È·›ˆ˜ ÁÈ· 8 ‚‰ÔÌ¿‰Â˜. MÂϤÙËÛ·Ó ÙÚÂȘ ÔÌ¿‰Â˜ Â›Ì˘ˆÓ, ÙȘ ÂÍ‹˜: Â›Ì˘Â˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ›¯Â ÚÔËÁËı› Ë ¯ÔÚ‹ÁËÛË ÈÒÓ ÚÈÓ ·fi ÙËÓ ¯ÔÚ‹ÁËÛË ÏÈÔÔÏ˘Û·Î¯·ÚÈÙÒÓ (Ì ÛÎÔfi ÙËÓ ÚfiÎÏËÛË ÂÚÈÔ‰ÔÓÙ›Ùȉ·˜), Â›Ì˘Â˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ‰ÂÓ Â›¯Â ÚÔËÁËı› Ë ¯ÔÚ‹ÁËÛË ÈÒÓ Ù˘ ¯ÔÚ‹ÁËÛ˘ ÏÈÔÔÏ˘Û·Î¯·ÚÈÙÒÓ Î·ıÒ˜ Î·È Â›Ì˘Â˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ¯ÔÚËÁ‹ıËΠÌfiÓÔ ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ ÙˆÓ ·‰ÂÓÔ˚ÒÓ ¯ˆÚ›˜ Ó· ·ÎÔÏÔ˘ı‹ÛÂÈ ¯ÔÚ‹ÁËÛË ÏÈÔÔÏ˘Û·Î¯·ÚÈÙÒÓ. O ·ÚÈıÌfi˜ ÙˆÓ ÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ¿ÚˆÓ ÛÙÔ Ê·ÙÓÈ·Îfi ÔÛÙÔ‡Ó Î·È ÛÙËÓ ˘ÔÂÈıËÏȷ΋ ÂÚÈÔ¯‹ ÌÂÙ¿ ·fi 4 ‚‰ÔÌ¿‰Â˜ Î·È ÛÙËÓ ˘ÔÂÈıËÏȷ΋ ÂÚÈÔ¯‹ ÌÂÙ¿ ·fi 8 ‚‰ÔÌ¿‰Â˜ ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚÔ˜ ÛÙËÓ ÔÌ¿‰· Â›Ì˘ˆÓ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ›¯Â ÚÔËÁËı› Ù˘ ÚfiÎÏËÛ˘ ÂÚÈÔ‰ÔÓÙ›Ùȉ·˜ Ë ¯ÔÚ‹ÁËÛË ÈÒÓ ¤Ó·ÓÙÈ ·˘ÙÒÓ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ‰ÂÓ Â›¯Â ÚÔËÁËı› Ë ¯ÔÚ‹ÁËÛË ÈÒÓ. E›Û˘, ÛÙËÓ ÔÌ¿‰· ÛÙËÓ ÔÔ›· ›¯Â ÚÔËÁËı› Ë ¯ÔÚ‹ÁËÛË ÈÒÓ ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚË ÁÚ·ÌÌÈ΋ ·ÒÏÂÈ· ÔÛÙÔ‡ ÛÙȘ 4 Î·È 8 ‚‰ÔÌ¿‰Â˜ ηٿ 61,2% Î·È 48,5%, ·ÓÙ›ÛÙÔȯ·. H ÔÁÎÔÌÂÙÚÈ΋ ·ÒÏÂÈ· ÔÛÙÔ‡ ‹Ù·Ó ›Û˘ ÌÂȈ̤ÓË Î·È Ë ÔÛÙÈ΋ ˘ÎÓfiÙËÙ· ·˘ÍË̤ÓË ÛÙËÓ ÔÌ¿‰· Û˘Ó‰˘·ÛÌÔ‡ ·‰ÂÓÔ˚ÒÓ Î·È ÏÈÔÔÏ˘Û·Î¯·ÚÈÙÒÓ. ¶·Ú’ fiÏ· ·˘Ù¿, ÌfiÓÔ Ë ‰È·ÊÔÚ¿ Ù˘ ÔÁÎÔÌÂÙÚÈ΋˜ ·ÒÏÂÈ·˜ ÙÔ˘ ÔÛÙÔ‡ ͤڷÛ ٷ fiÚÈ· Ù˘ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈÎfiÙËÙ·˜ ÛÙȘ 8 ‚‰ÔÌ¿‰Â˜ ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ. ™ÙËÓ ÔÌ¿‰· ÛÙËÓ ÔÔ›· ›¯Â ÚÔËÁËı› Ë ¯ÔÚ‹ÁËÛË ÈÒÓ ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚÔ˜ ·ÚÈıÌfi˜ ÔÛÙÂÔÎÏ·ÛÙÒÓ, ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο 66 17. Zheng Y, Liu Y, Zhang CM, Zhang HY, Li WH, Shi S et al: Stem cells from deciduous tooth repair mandibular defect in swine. J Dent Res 2009; 88 (3): 249-54. 18. Zhang L, Wang P, Mei S, Li C, Cai C, Ding Y: In vivo alveolar bone regeneration by bone marrow stem cells/fibrin glue composition. Arch Oral Biol 2012; 57 (3): 238-44. 19. Hasegawa N, Kawaguchi H, Hirachi A, Takeda K, Mizuno N, Nishimura M et al: Behacior of transplanted bone marrowderived mesenchymal stem cells in periodontal defects. J Periodontol 2006; 77: 1003-07. 20. Kawaguchi H, Hirachi A, Hasegawa N, Iwata T, Hamaguchi H, Shiba H et al: Enhancement of periodontal tissue regeneration by transplantation of bone marrow mesenchymal stem cells. J Periodontol 2004; 75: 1281-87. 21. Li H, Yan F, Lei L, Li Y, Xiao Y: Application of autologous cryopreserved bone marrow mesenchymal stem cells for periodontal regeneration in dogs. Cells Tissues Organs 2009; 190 (2): 94-101. 22. 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Chang P-C, Cirelli J, Jin Q, Seol Y-J, Sungai JV, D’Silva N et al: Adenovirus encoding human platelet-derived growth factor-B delivered to alveolar bone defects exhibits safety Hellenic Stomatological Review 57: 39-71, 2013 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ÌÈÎÚfiÙÂÚË ÂÈÊ¿ÓÂÈ· Ê·ÙÓÈ·ÎÔ‡ ÔÛÙÔ‡ Û ·ʋ Ì ÔÛÙÂÔÎÏ·ÛÙÈο ·ÙÙ·Ú· (ÛÙȘ 4 Î·È 8 ‚‰ÔÌ¿‰Â˜) ηıÒ˜ Î·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚË ¤ÎÊÚ·ÛË ÈÓÙÂÚÏ¢ΛÓ˘-6 (IL-6), ÈÓÙÂÚÏ¢ΛÓ˘-10 (IL-10), Û˘Ó‰¤ÙË ÙÔ˘ ÂÓÂÚÁÔÔÈËÙ‹ ÙÔ˘ ˘Ô‰Ô¯¤· ÙÔ˘ ˘ÚËÓÈÎÔ‡ ·Ú¿ÁÔÓÙ·kB (Receptor activator of nuclear factor-kB ligand, RANKL) Î·È ÔÛÙÂÔÚÔÙÂÁÂÚ›Ó˘ (OPG) (ÛÙȘ 4 ‚‰ÔÌ¿‰Â˜) ¤Ó·ÓÙÈ Ù˘ ÔÌ¿‰·˜ ÛÙËÓ ÔÔ›· ‰ÂÓ Â›¯Â ÚÔËÁËı› Ë ¯ÔÚ‹ÁËÛË ÈÒÓ. ™‡ÁÎÚÈÛË ÌÂٷ͇ Ù˘ ÔÌ¿‰·˜ ÛÙËÓ ÔÔ›· ›¯Â ÚÔËÁËı› Ë ¯ÔÚ‹ÁËÛË ÈÒÓ ÚÈÓ ÙË ¯ÔÚ‹ÁËÛË ÏÈÔÔÏ˘Û·Î¯·ÚÈÙÒÓ Î·È Ù˘ ÔÌ¿‰·˜ ÛÙËÓ ÔÔ›· ¯ÔÚËÁ‹ıËΠÌfiÓÔ ÙÔ Ì¤ÛÔ ÌÂÙ·ÊÔÚ¿˜ ÙˆÓ ·‰ÂÓÔ˚ÒÓ ¯ˆÚ›˜ Ó· ·ÎÔÏÔ˘ı‹ÛÂÈ ¯ÔÚ‹ÁËÛË ÏÈÔÔÏ˘Û·Î¯·ÚÈÙÒÓ ¤‰ÂÈÍ ·ÚfiÌÔÈÔ ·ÚÈıÌfi ÔÛÙÂÔÎÏ·ÛÙÒÓ Î·ıÒ˜ Î·È ·ÚfiÌÔÈ· ¤ÎÊÚ·ÛË IL-6, IL-10, RANKL, OPG, ÈÓÙÂÚÏ¢ΛÓ˘-1‚ (IL-1‚) Î·È TNF-· ÌÂٷ͇ ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ. EÈÚfiÛıÂÙ·, Ù· ›‰· ¤ÎÊÚ·Û˘ ÙˆÓ IL-1‚ Î·È TNF-· ‹Ù·Ó ·ÚfiÌÔÈ· Î·È ÁÈ· ÙȘ ÙÚÂȘ ÔÌ¿‰Â˜45. ™ÙËÓ ›‰È· ÌÂϤÙË, ‰È·ÈÛÙÒıËΠˆ˜ ÌÂÙ¿ ·fi 24 ¤ˆ˜ 48 ÒÚ˜, Ë ÔÌ¿‰· ÛÙËÓ ÔÔ›· ¯ÔÚËÁ‹ıËÎ·Ó ÌfiÓÔ ÏÈÔÔÏ˘Û·Î¯·Ú›Ù˜ ·ÚÔ˘Û›·Û ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ¤ÎÊÚ·ÛË IL-1‚ Î·È TNF-· Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÛÙËÓ ÔÔ›· ¯ÔÚËÁ‹ıËΠÌfiÓÔ ÙÔ Ì¤ÛÔ ¯ÔÚ‹ÁËÛ˘ ÙˆÓ ·‰ÂÓÔ˚ÒÓ ¯ˆÚ›˜ Ó· ·ÎÔÏÔ˘ı‹ÛÂÈ ¯ÔÚ‹ÁËÛË ÏÈÔÔÏ˘Û·Î¯·ÚÈÙÒÓ. H ÔÌ¿‰· ÛÙËÓ ÔÔ›· ÚÔËÁ‹ıËÎÂ Ë ¯ÔÚ‹ÁËÛË ·‰ÂÓÔ˚ÒÓ ·ÚÔ˘Û›·Û ›Û˘ ÌÂÁ·Ï‡ÙÂÚ· ›‰· ¤ÎÊÚ·Û‹˜ ÙÔ˘˜, Ô˘ ÍÂ¤Ú·Û·Ó ÙÔ fiÚÈÔ Ù˘ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈÎfiÙËÙ·˜ ÛÙȘ 48 ÒÚ˜, ˆÛÙfiÛÔ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÈÎÚfiÙÂÚ· Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÛÙËÓ ÔÔ›· ¯ÔÚËÁ‹ıËÎ·Ó ÌfiÓÔ ÏÈÔÔÏ˘Û·Î¯·Ú›Ù˜. TÔ ÁÂÁÔÓfi˜ ·˘Ùfi ˘Ô‰ËÏÒÓÂÈ ˆ˜ Ë ·Ó·ÛÙ·ÏÙÈ΋ ‰Ú¿ÛË ÙÔ˘ ˘Ô‰Ô¯¤· ÙÔ˘ TNF-· ÛÙËÓ ¤ÎÊÚ·ÛË ·˘ÙÒÓ ÙˆÓ ÌÂÛÔÏ·‚ËÙÒÓ Ù˘ ÊÏÂÁÌÔÓ‹˜ Â›Ó·È ÂÚÈÛÛfiÙÂÚÔ ÂÌÊ·Ó‹˜ ‚Ú·¯˘ÚfiıÂÛÌ·. A˘Ùfi ›Ûˆ˜ Ó· ÔÊ›ÏÂÙ·È ÛÙË Ì›ˆÛË Ù˘ ÚÔ·ÁfiÌÂÓ˘ ·fi ÙÔ˘˜ ÏÈÔÔÏ˘Û·Î¯·Ú›Ù˜ ¤ÎÊÚ·Û˘ ÙˆÓ ÌÂÛÔÏ·‚ËÙÒÓ Ù˘ ÊÏÂÁÌÔÓ‹˜ Ì ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘, ÂÍ·ÈÙ›·˜ Ù˘ ·Ó¿Ù˘Í˘ ·ÓÙÔ¯‹˜ ÙÔ˘ ÍÂÓÈÛÙ‹ ¤Ó·ÓÙÈ ÙˆÓ ÂÓ‰ÔÙÔÍÈÓÒÓ Ì ÛÎÔfi ÙË Ú‡ıÌÈÛË Ù˘ ÙÔÈ΋˜ ·ÓÔÛÔÏÔÁÈ΋˜ ·¿ÓÙËÛ˘45. ÕÏÏÔÈ ÙÚfiÔÈ ÌÂÙ·ÊÔÚ¿˜ ÁÔÓȉ›ˆÓ Œ¯ÂÈ ÚÔÙ·ı› fiÙÈ ÌÂٷ͇ ÙˆÓ ÌË È˚ÎÒÓ ÊÔÚ¤ˆÓ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡, Ù· Ï·ÛÌ›‰È· ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ÁÈ· ÙË ÌÂÙ·ÊÔÚ¿ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÛÙË ÁÔÓȉȷ΋ ıÂڷ›· ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ. OÈ Chen Î·È Û˘Ó.46 ÌÂϤÙËÛ·Ó ÙËÓ ¤ÎÊÚ·ÛË ÏÔ˘ÛÈÊÂÚ¿Û˘ ÌÂÙ¿ ·fi ÌÂÙ·ÊÔÚ¿ Ï·ÛÌȉ›ˆÓ ·Ó·Û˘Ó‰˘·ÛÌ¤ÓˆÓ ÒÛÙ ӷ ÂÚȤ¯Ô˘Ó ÙÔ ÁÔÓ›‰ÈÔ Ù˘ ÏÔ˘ÛÈÊÂÚ¿Û˘ Û ÂÚÈÔ‰ÔÓÙÈÎÔ‡˜ ÈÛÙÔ‡˜ Â›Ì˘ˆÓ Ì ÙË ‚Ô‹ıÂÈ· Ó·ÓfiÊÔ˘ÛÎˆÓ Î·È ˘ÂÚ˯ËÙÈÎÒÓ Î˘Ì¿ÙˆÓ (ÂÚÈfi‰Ô˘ 10Ìs Î·È ÂÓ¤ÚÁÂÈ·˜ 36J/cm2). ™ÙËÓ ÔÌ¿‰· Â›Ì˘ˆÓ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ¤ÁÈÓ ¯ÔÚ‹ÁËÛË Ï·ÛÌȉ›ˆÓ ·Ó·ÌÂÌÂÈÁÌ¤ÓˆÓ Ì ӷÓfiÊÔ˘ÛΘ ·ÎÔÏÔ˘ıÔ‡ÌÂÓË ·fi ÂÊ·ÚÌÔÁ‹ ˘ÂÚ˯ËÙÈÎÒÓ Î˘Ì¿ÙˆÓ ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ÌÂÁ·Ï‡ÙÂÚË ¤ÎÊÚ·ÛË ÏÔ˘ÛÈÊÂÚ¿Û˘ ÙËÓ ÚÒÙË Ë̤ڷ Û ۇÁÎÚÈÛË Ì ÙË ¯ÔÚ‹ÁËÛË ÌfiÓÔ Ï·ÛÌȉ›ˆÓ, ÙË ¯ÔÚ‹ÁËÛË Ï·ÛÌȉ›ˆÓ ·Ó·ÌÂÌÂÈÁÌ¤ÓˆÓ Ì ӷÓfiÊÔ˘ÛΘ Î·È ÙË ¯ÔÚ‹ÁËÛË ÌfiÓÔ Ï·ÛÌȉ›ˆÓ ·ÎÔÏÔ˘ıÔ‡ÌÂÓË ·fi ÂÊ·ÚÌÔÁ‹ ˘ÂÚ˯ËÙÈÎÒÓ Î˘Ì¿ÙˆÓ. øÛÙfiÛÔ, ÙËÓ ÙÚ›ÙË Ë̤ڷ Ë ¤ÎÊÚ·ÛË Ù˘ ÏÔ˘ÛÈÊÂÚ¿Û˘ ÂHellenic Stomatological Review 57: 39-71, 2013 and biodistribution profiles favorable for clinical use. Hum Gene Ther 2009; 20: 486-96. 34. Chen YL, Chen PK, Jeng LB, Huang CS, Yang LC, Chung HY et al: Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty. Gene Ther 2008; 15 (22): 146977. 35. Sun QF, Zhu XM, Yang PS, Liu Y, DU F: Gene therapy of bone morphogenetic protein-2 for periodontal tissue regeneration in vivo.Shanghai Kou Qiang Yi Xue 2007; 16 (2): 211-14. 36. Tan Z, Zhao Q, Gong P, Wu Y, Wei N, Yuan Q et al: Research on promoting periodontal regeneration with human basic fibroblast growth factor-modified bone marrow mesenchymal stromal cell gene therapy. Cytotherapy 2009; 11 (3): 317-25. 37. Li YF, Yan FH, Zhong Q, Zhao X: Effect of hBMP-7 gene modified bone marrow stromal cells on periodontal tissue regeneration. Zhonghua Yi Xue Za Zhi 2010 25; 90 (20): 1427-30. 38. Zhang Y, Song J, Shi B, Wang Y, Chen X, Huang C et al: Combination of scaffold and adenovirus vectors expressing bone morphogenetic protein-7 for alveolar bone regeneration at dental implant defects. Biomaterials 2007; 28 (31): 4635-42. 39. Zhou W, Zhao CH, Mei LX: Effect of the compound of poly lactic-co-glycolic acid and bone marrow stromal cells modified by osteoprotegerin gene on the periodontal regeneration in Beagle dog periodontal defects. Hua Xi Kou Qiang Yi Xue Za Zhi 2010; 28 (3): 324-9. 40. Chang P-C, Seol Y-J, Cirelli JA, Pellegrini GR, Jin Q, Franco LM et al: PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration. Gene Ther 2010; 17 (1): 95-104. 41. Chung VH-Y, Chen AY-L, Kwan C-C, Chen PK-T, Chang SC-N: Mandibular alveolar bony defect repair using bone morphogenetic protein 2-expressing autologous mesenchymal stem cells. J Craniofac Surg 2011; 22 (2): 450-54. 42. 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Kondylis e-mail: [email protected] 67 μÈ‚ÏÈÔÁÚ·ÊÈ΋ ∞Ó·ÛÎfiËÛË Literature Review ¤ÛÙÚ„ ÛÙ· ·Ú¯Èο ›‰· Û ·˘Ù‹ ÙËÓ ÔÌ¿‰·. OÈ ÂÚ¢ÓËÙ¤˜ ˘ÔÛÙ‹ÚÈÍ·Ó ˆ˜ Ë ‰È¿ÚÚËÍË ·fi Ù· ˘ÂÚ˯ËÙÈο ·̷ٷ ÙˆÓ Ó·ÓfiÊÔ˘ÛÎˆÓ Î·È ÙˆÓ Ê˘ÛÛ·Ï›‰ˆÓ Ô˘ ‰ËÌÈÔ˘ÚÁ‹ıËÎ·Ó ·fi ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙˆÓ ˘ÂÚ˯ËÙÈÎÒÓ Î˘Ì¿ÙˆÓ ÚÔοÏÂÛ ·ÚÔ‰È΋ ·‡ÍËÛË Ù˘ ‰È·ÂÚ·ÙfiÙËÙ·˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ì ·ÔÙ¤ÏÂÛÌ· ›ÛÔ‰Ô ÙˆÓ Ï·ÛÌȉ›ˆÓ Û ·˘Ù¿. T· ˘ÂÚ˯ËÙÈο ·̷ٷ Ê·›ÓÂÙ·È fiÙÈ ı· Ú¤ÂÈ Ó· Â›Ó·È ÌÈÎÚ‹˜ ‰È¿ÚÎÂÈ·˜, ÂÊ’ fiÛÔÓ Î‡Ì·Ù· ÌÂÁ¿Ï˘ ‰È¿ÚÎÂÈ·˜ ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÌË ·ÓÙÈÛÙÚÂÙ‹ ·‡ÍËÛË Ù˘ ‰È·ÂÚ·ÙfiÙËÙ·˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ, ηıÒ˜ Î·È Ó· Â›Ó·È ¯·ÌËÏ‹˜ ÂÓ¤ÚÁÂÈ·˜, ÂÊ’ fiÛÔÓ ·˘ÍË̤ÓË ÂÓ¤ÚÁÂÈ· ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ì›ˆÛË Ù˘ ˙ˆÙÈÎfiÙËÙ¿˜ ÙÔ˘˜. H ÌÈÎÚ‹˜ ‰È¿ÚÎÂÈ·˜ ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ Ô˘ ÌÂٷʤÚÔÓÙ·È Ì ·˘ÙfiÓ ÙÔÓ ÙÚfiÔ Î·È Î·ıÈÛÙÔ‡Ó ÂȂ‚ÏË̤ÓË ÙËÓ Ù·ÎÙÈ΋ ·ӿÏË„Ë Ù˘ ıÂڷ›·˜ ÁÈ· ÙË ‰È·Ù‹ÚËÛË ˘„ËÏÔ‡ ÂȤ‰Ô˘ ¤ÎÊÚ·Û˘ ÙˆÓ ÁÔÓȉ›ˆÓ, Èı·ÓfiÓ Ó· ÔÊ›ÏÂÙ·È Û ٷ¯Â›· ·Ô‰fiÌËÛË ÙˆÓ Ï·ÛÌȉ›ˆÓ ÂÍ·ÈÙ›·˜ Ù˘ ¿ÊıÔÓ˘ ·ÈÌ¿ÙˆÛ˘ Ù˘ ÂÚÈÔ¯‹˜. Œ¯ÂÈ ÚÔÙ·ı› fiÙÈ Ë Â¤ÎÙ·ÛË Ù˘ ‰È¿ÚÎÂÈ·˜ ¤ÎÊÚ·Û˘ ÙˆÓ ÁÔÓȉ›ˆÓ Èı·Ó¿ Ó· Â›Ó·È ÂÊÈÎÙ‹ Ì ‚ÂÏÙÈÛÙÔÔ›ËÛË ÙˆÓ ·Ú·Ì¤ÙÚˆÓ ÙˆÓ ˘ÂÚ˯ËÙÈÎÒÓ Î˘Ì¿ÙˆÓ Î·È Ì ÙËÓ ·Ó¿Ù˘ÍË Û˘Û΢‹˜ ·Ú·ÁˆÁ‹˜ ˘ÂÚ˯ËÙÈÎÒÓ Î˘Ì¿ÙˆÓ ÂÍÂȉÈÎÂ˘Ì¤Ó˘ ÁÈ· ÙÔ ÛÎÔfi ·˘Ùfi46. ™YM¶EPA™MATA H ÂÈÙ˘¯‹˜ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ ‚·Û›˙ÂÙ·È ÛÙËÓ ‡·ÚÍË Î˘ÙÙ¿ÚˆÓ, ΢ÙÙ·ÚÈÎÒÓ ÛËÌ¿ÙˆÓ Ô˘ Ú˘ıÌ›˙Ô˘Ó ÙËÓ Î˘ÙÙ·ÚÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ·, ÈÎÚÈˆÌ¿ÙˆÓ Ô˘ ˘ÔÛÙËÚ›˙Ô˘Ó ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Î·È ·ÈÌ¿ÙˆÛ˘ ÁÈ· ÙËÓ ÂÍ·ÛÊ¿ÏÈÛË Ù˘ ÔÔ›·˜ Û˘ÌÌÂÙ¤¯Ô˘Ó ΢ÙÙ·ÚÈο Û‹Ì·Ù· ηıÒ˜ Î·È ÛÙÔÓ ¤ÏÂÁ¯Ô ÙÔ˘ ÌÈÎÚÔ‚È·ÎÔ‡ ·Ú¿ÁÔÓÙ·. H ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ ‚Ï·ÛÙÔ΢ÙÙ¿ÚˆÓ ·Ú¤¯ÔÓÙ·˜ Ó¤· ·ÙÙ·Ú· Ù· ÔÔ›· ÔÏÏ·Ï·ÛÈ·˙fiÌÂÓ·, ‰È·ÊÔÚÔÔÈÔ‡ÌÂÓ· Î·È ÂÎÎÚ›ÓÔÓÙ·˜ ΢ÙÙ·ÚÈο Û‹Ì·Ù· Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ÈÛÙÈ΋ ·‡ÍËÛË Î·È ‰È·ÊÔÚÔÔ›ËÛË ¤¯ÂÈ ·ÚÔ˘ÛÈ¿ÛÂÈ ÂÓı·ÚÚ˘ÓÙÈο ·ÔÙÂϤÛÌ·Ù· ÛÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Î˘Ú›ˆ˜ Û ÚÔÎÏÈÓÈÎfi Â›Â‰Ô Î·È ÌÂÏÂÙ¿Ù·È Û ÎÏÈÓÈÎfi ›‰Ô. ¶·Ú¿ÏÏËÏ·, ÂÓı·ÚÚ˘ÓÙÈο ·ÔÙÂϤÛÌ·Ù· ÛÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ Û ÚÔÎÏÈÓÈÎfi Â›Â‰Ô ¤¯ÂÈ ·ÚÔ˘ÛÈ¿ÛÂÈ Ë ÌÂÙ·ÊÔÚ¿ ÁÔÓȉ›ˆÓ, Ë ÔÔ›· ‰›ÓÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ¤ÎÊÚ·Û˘ ΢ÙÙ·ÚÈÎÒÓ ÛËÌ¿ÙˆÓ ·fi Ù· ·ÙÙ·Ú·-ÛÙfi¯Ô˘˜ Ì ÛÎÔfi ÙËÓ Â·ÁˆÁ‹ Ù˘ ÈÛÙÈ΋˜ ·‡ÍËÛ˘ Î·È ‰È·ÊÔÚÔÔ›ËÛ˘ ‹ ÙÔÓ ¤ÏÂÁ¯Ô Ù˘ ·ÓÔÛÔÏÔÁÈ΋˜ ·¿ÓÙËÛ˘ ÙÔ˘ ÍÂÓÈÛÙ‹ Û ÌÈÎÚԂȷο ÂÚÂı›ÛÌ·Ù·, Ô˘ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÂËÚ¿ÛÂÈ ·ÚÓËÙÈο ÙÔ ıÂڷ¢ÙÈÎfi ·ÔÙ¤ÏÂÛÌ·. OÈ Ù¯ÓÈΤ˜ ·˘Ù¤˜ ÂÊ·ÚÌÔ˙fiÌÂÓ˜ ·ÓÂÍ¿ÚÙËÙ· ‹ Û˘Ó‰˘·˙fiÌÂÓ˜ ÌÂٷ͇ ÙÔ˘˜ Èı·Ó¿ Ó· ÚÔÛʤÚÔ˘Ó ÂÈÚfiÛıÂÙ· ÔʤÏË ÛÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÂÚÈÔ‰ÔÓÙÈÎÒÓ ÈÛÙÒÓ, Ù· ÔÔ›· ‰ÈÂÚÂ˘Ó¿ Ë Û˘Ó¯È˙fiÌÂÓË ¤Ú¢ӷ Ô˘ ÂÈÙÂÏÂ›Ù·È Û ·˘Ùfi ÙÔ Â‰›Ô. BIB§IO°PAºIA 1. ¶ÂÂÏ¿ÛË E, •˘ÓÔÁ·Ï¿ I: H ÛËÌÂÚÈÓ‹ ı¤ÛË ÙˆÓ ·Ó·Ï·ÛÙÈÎÒÓ Ù¯ÓÈÎÒÓ. 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