XXXII Scuola Annuale di Bioingegneria
(Approccio integrato per la medicina rigenerativa)
Bressanone, 16-20 Settembre 2013
Attuatori bio-ibridi
Arianna Menciassi, Leonardo Ricotti
The BioRobotics Institute
Scuola Superiore Sant’Anna (Pisa)
Come si colloca questa lezione nell’ambito della Scuola
Well established technologies in a field which can be
disruptive in a different field
Christensen , "The Innovator's Dilemma“ (1997): new technology are
separated into two categories: sustaining and disruptive. Sustaining
technology relies on incremental improvements to an already
established technology. Disruptive technology lacks refinement, often
has performance problems because it is new, appeals to a limited
audience, and may not yet have a proven practical application.
+
Traditional endoscope
CMOS cameras and
high power LEDs
=
Endoscopic pills
Come si colloca questa lezione nell’ambito della Scuola
...
The link between this lecture and the GNB School
topics
Technologies for tissue engineering, related to cell culturing,
scaffolding, differentiation etc. can be applied in fields different
from regenerative medicine with a dramatic impact.
?
Sommario
Outline
• Il problema dell’attuazione nella
progettazione e sviluppo di macchine
• I vantaggi del muscolo naturale
• Approccio ibrido all’attuazione
• Problemi da risolvere per costruire attuatori
bioibridi usabili
• Esempi di lavori in corso
• Conclusioni e contributi da e per il tissue
engineering
Sommario
Outline
• Il problema dell’attuazione nella
progettazione e sviluppo di macchine
• I vantaggi del muscolo naturale
• Approccio ibrido all’attuazione
• Problemi da risolvere per costruire attuatori
bioibridi usabili
• Esempi di lavori in corso
• Conclusioni e contributi da e per il tissue
engineering
Il problema dell’attuazione nella progettazione e sviluppo di macchine
Future machines: the bottleneck of actuation
Actuation is an essential function of any artificial or living machine, allowing
its movement and its interaction with the surrounding environment…
Micro-machines are limited
by scalability issues
Large machines are characterized by lack of
flexibility and of life-like movements
A hot topic already in 2005
(GNB School by Giusti and Cigada)
Il problema dell’attuazione nella progettazione e sviluppo di macchine
Large machines: lack of flexibility and life-like movements
NAO robot
Roberto Bolle
http://www.youtube.com/watch?v=2laujomh0JY
http://www.youtube.com/watch?v=Kb3VNPsugWk
• Rigid constitutive
elements and joints
• Non-compliant actuators
• Centralized intelligence
• …
• Flexible constitutive
elements and joints
• Compliant actuators
(muscles)
• Distributed
intelligence
• …
Il problema dell’attuazione nella progettazione e sviluppo di macchine
...
Small machines: scalability issues
At small scales, the relative importance of the physical laws changes
L = characteristic length
Volumetric quantities: inertia, weight,
heat capacity, body forces
Surface quantities: friction, heat
transfer, surface forces
Intermolecular van
der Waals force:
𝐹𝑣𝑑𝑊 =
Scale as
~ L3
Scale as
~ L2
𝐻𝑟
8π𝑥 2
http://www.youtube.
com/watch?v=hjiVViMuS4
H = material-dependent Hamaker constant
r = radius of a sphere
x = separation distance (sphere – infinite halfspace)
Scales as ~ L , if only r scales
Scales as ~ L-1 , if both r and x scale
J.J. Abbott et al. Robotics in the small. IEEE
Rob Autom Mag. 14: 92-103 (2007)
Il problema dell’attuazione nella progettazione e sviluppo di macchine
Force vs Size - Comparative analysis
(Scuola GNB 2005 – “Attuatori e Sensori”, Dario, Menciassi, Stefanini)
Il problema dell’attuazione nella progettazione e sviluppo di macchine
Comparison between actuator technologies
M. Zupan et al. Actuator classification and selection – the development
of a database. Adv. Eng. Mat. 4(12): 933-939 (2002)
Il problema dell’attuazione nella progettazione e sviluppo di macchine
Comparison between actuator technologies
Piezoelectric motors
Converse piezoelectric effect: change in shape when an electrical field is applied
Acoustic or ultrasonic vibrations
Linear or rotary motion
Delta-3 demonstrator,
by Noliac
http://www.youtube.c
om/watch?v=OJj18
mqO1YM
http://www.youtube.com/watch?v=
CYcVT1yFv7A
 High-precision positioning
 Fast actuation (high frequency)
 Extremely limited stroke
…
Il problema dell’attuazione nella progettazione e sviluppo di macchine
Comparison between actuator technologies
M. Zupan et al. Actuator classification and selection – the development
of a database. Adv. Eng. Mat. 4(12): 933-939 (2002)
Il problema dell’attuazione nella progettazione e sviluppo di macchine
Comparison between actuator technologies
Pneumatic actuators
Conversion of energy (tipically in the form of compressed air) into mechanical (linear or
rotary) motion
McKibben surgical robot, by KU Leuven
http://www.youtube.com/watch?v=4oeZ
bD_nYfs
http://www.youtube.com/watch?v
=xL5bInUumbM
 Good compromise between force output and stroke
 Mimicking of few muscle features
 Need of an extremely bulky energy source
…
Sommario
Outline
• Il problema dell’attuazione nella
progettazione e sviluppo di macchine
• I vantaggi del muscolo naturale
• Approccio ibrido all’attuazione
• Problemi da risolvere per costruire attuatori
bioibridi usabili
• Esempi di lavori in corso
• Conclusioni e contributi da e per il tissue
engineering
I vantaggi del muscolo naturale
The unique properties of muscles
Natural muscles rely on a finely regulated acto-myosin contractile
machinery, optimized by millions of years of natural evolution.
Benz Patent Motor Car
B. Trimmer. A journal of soft robotics: why now? Soft Robotics. 1: 1-4 (2013)
I vantaggi del muscolo naturale
Non-key skeletal muscle features
J.M. Hollerbach et al. Comparative analysis of actuator technologies for robotics.
The Rob. Rev. 2. 299-341 (1992)
I vantaggi del muscolo naturale
Key skeletal muscle features
• Backdrivability
• Stiffness control
• High transduction efficiency
• Self-sensing / self-healing properties
• Chemically fueling
• High aerobic transduction efficiency
(1000 J per gram of glucose)
D.G. Caldwell. Natural and artificial
muscle elements as robot actuators.
Mechatronics. 3: 269-283 (1993)
No artificial actuators are able to
reproduce the behavior of muscle integrated
series-elastic components, which are thought
to give rise to many of the “life-like” characteristics of animal movements.
S. Lv et al. Designed biomaterials to mimic the mechanical
properties of muscles. Nature. 465: 69-73 (2010)
I vantaggi del muscolo naturale
Key skeletal muscle features
Natural muscle has a
modular architecture based
on microscopic contractile
units (the acto-myosin
molecular machinery)
Performance invariance at
both small and large
scales
http://www.youtube.com/watch?v=gJ309LfHQ3M
Meccanismi o materiali smart per l’attuazione
How obtaining muscle-like behaviour
Design of smart mechanisms
Development of a bio-inspired robotic hand:
40 artificial actuators: non
feasible, due to:
Natural hand: ~ 40 muscles
• System bulkyness
• Unavailability of 40
different control signals
Underactuated mechanisms require few
control signals but can still endow the hand
with many degrees of freedom (DOFs).
Underactuated mechanisms:
# Actuators < # DOFs
2 motors , 9 DOFs
E. Mattar. A survey of bio-inspired robotics hand
implementation: new directions in dexterous
manipulation. Rob. Auton. Syst. 61: 517-544 (2013)
Meccanismi o materiali smart per l’attuazione
How obtaining muscle-like behaviour
Design of smart mechanisms
Real OCTOPUS
arm
Artificial
OCTOPUS arm
Local processing,
wires
Transverse actuation
system
Longitudinal Muscles
Transverse Muscles
Oblique Muscles
Longitudinal
actuation system
Embedding material
Mechanical interface
/ containment
(nylon)
C. Laschi et al. Design of a biomimetic robotic octopus arm. Bioinspir. Biomim. 4(1):
(2009)
M. Cianchetti et al. Design concept and validation of a robotic arm inspired by the
octopus. Mat. Sci. Eng.: C. 31: 1230-1239 (2011)
Meccanismi o materiali smart per l’attuazione
How obtaining muscle-like behaviour
Design of smart mechanisms
C. Laschi et al. Design of a biomimetic robotic octopus arm. Bioinspir. Biomim. 4(1):
(2009)
M. Cianchetti et al. Design concept and validation of a robotic arm inspired by the
octopus. Mat. Sci. Eng.: C. 31: 1230-1239 (2011)
Meccanismi o materiali smart per l’attuazione
How obtaining muscle-like behaviour
Biomimetic actuators based on smart materials
Electroactive polymers (EAPs)
Polymers that exhibit a change in size or shape when stimulated by an electric field
•
•
•
•
•
Dielectric elastomers
Conductive polymers
Ionic polymer metal composites
Polyelectrolyte mechano-chemical gels
Piezoelectric polymers
Flex robot, by
SRI International
http://www.youtu
be.com/watch?v
=nl4-s-DDO-M
Spring Roll actuator, by
SRI International
http://www.youtube.com/w
atch?v=eIh8L59sd30
Robot blimp, by Swiss Federal Lab for Materials Testing and Research
http://www.youtube.com/watch?v=6cdfWdHZRrE
Sommario
Outline
• Il problema dell’attuazione nella
progettazione e sviluppo di macchine
• I vantaggi del muscolo naturale
• Approccio ibrido all’attuazione
• Problemi da risolvere per costruire attuatori
bioibridi usabili
• Esempi di lavori in corso
• Conclusioni e contributi da e per il tissue
engineering
La soluzione: crescere muscoli naturali interfacciandoli con meccanismi artificiali
Explanted living muscles-based devices
12 cm
Muscle-powered swimming robot:
• Autonomy: 4 h
• Speed: 1/3 body length / s
H. Herr et al. A swimming robot actuated by living
muscle tissue. J. Neuroeng. Rehab. 1: 1-6 (2004)
Main drawbacks:
• need of sacrificing vertebrate animals;
• extremely limited lifetime (explanted muscles are characterized by
functional structures, such as the vascular network, which rapidly
degenerate out of their native environment);
• possible actuator architectures are limited by the
those available in nature.
La soluzione: crescere muscoli naturali interfacciandoli con meccanismi artificiali
...
Self-beating cardiomyocyte-based devices
•
Speed: 38 µm/s = 2.3 mm/min (1/4 body length / s)
J. Xi et al. Self-assembled microdevices driven by muscle. Nature. 4:
180-184 (2005)
100 µm
La soluzione: crescere muscoli naturali interfacciandoli con meccanismi artificiali
...
Self-beating cardiomyocyte-based devices
(meso scale device with scalability potentialities)
A.W. Feinberg et al. Muscular thin
films for building actuators and
powering devices. Science.
317: 1366-1370 (2007)
1 mm
•
Speed: 3 mm/min [24 mm/min if paced
at 1 Hz (10 V stimulation)]
La soluzione: crescere muscoli naturali interfacciandoli con meccanismi artificiali
Self-beating cardiomyocyte-based devices
𝐹=
𝐸𝑎𝑏3
4𝐿3
𝑥
F = bending force
E = hydrogel elastic modulus
x = micropillar displacement
F ~ 80 nN (larger than forces generated by molecular
motors or laser tweezers: typically, few pN)
K. Morishima et al. Demonstration of a bio-microactuator
powered by cultured cardiomyocytes coupled to hydrogel
micropillars. Sens Act B: Chem.
119: 345-350 (2006)
Cardiomyocyte-actuated micropump
Microchannel flow rate: 2 nL/min
(typical flow rate for a microchamber: 100 nL/min)
Y. Tanaka et al. An actuated pump on-chip powered by
cultured cardiomyocytes. Lab Chip.
6: 362-368 (2006)
La soluzione: crescere muscoli naturali interfacciandoli con meccanismi artificiali
...
Self-beating insect cell-based devices
Mammals
~ 37°C / precise pH values
Larvae of Ctenoplusia agnate
4 – 40 °C / wide range of pH
•
Operability at room
temperature (25° C)
•
Long-term stability, even
without medium replacement
(~ 30 days)
•
Speed: 3.5
µm/s (almost
in straight
line)
Y. Akiyama et al. Room temperature operable
autonomously moving bio-microrobot powered
by insect dorsal vessel tissue. PLoS ONE.
7: e38274 (2012)
La soluzione: crescere muscoli naturali interfacciandoli con meccanismi artificiali
...
Skeletal muscle-based devices
K. Nagamine et al. Spatiotemporally
controlled contraction of
micropatterned skeletal muscle cells
on a hydrogel sheet. Lab Chip.
11: 513-517 (2011)
M.S. Sakar et al. Formation and optogenetic control of
engineered 3D skeletal muscle bioactuators. Lab Chip.
12: 4976-4985 (2012)
• Limited myotube maturation / low
contractility
• Short-term stability
La soluzione: crescere muscoli naturali interfacciandoli con meccanismi artificiali
Comparison between actuator technologies
Cardiomyocytebased devices
Skeletal musclebased devices
Modeling of bio-hybrid systems
For optimizing the device behaviur, modelling can help
Multi-scale and multi-purpose modeling
Aspect to model
Type of modeling
Instruments
Cell-substrate interaction
and device contraction
Non-linear hyperelastic
and cell-based models
Finite element tools (e.g.
Abaqus)
Electrical stimulation,
fluidic renewal, etc.
Modeling of combined
physical effects
Multiphysics analysis tools
(e.g. COMSOL)
Cell/protein engineering
(e.g. due to cellnanoparticle interactions)
Modeling of
micro/nanoscale
phenomena and quantum
effects
Molecular Dynamics (MD)
simulations (e.g. NAMD2
software)
Modeling of bio-hybrid systems
Cell-substrate interaction and device contraction: an example
of modeling strategy
Modeling of muscle thin films:
Deformation gradient:
𝜕𝑥
𝐹=
𝜕𝑋
X = reference position
x = current position
J. Shim et al. Modeling of cardiac muscle thin films: pre-stretch, passive
and active behavior. J. Biomech. 45: 832-841 (2012)
Modeling of bio-hybrid systems
Cell-substrate interaction and device contraction: an example
of modeling strategy
Elastomeric substrate
Muscle cells
Cauchy stress
(for an elastomeric substrate)
Neo-Hookean model:
Cauchy stress
(for beating cardiomyocytes)
Phenomenological model:
𝑻 = 𝑻𝒗 + 𝑻𝒊𝒔𝒐𝒕 + 𝑻𝒂𝒏𝒊 𝒑𝒂𝒔 + 𝑻𝒂𝒏𝒊(𝒂𝒕𝒕)
𝑻 = 𝑻𝒗 + 𝑻𝒊𝒔𝒐𝒕
𝐸
𝑇 = 𝑘(J − 1) + 3𝐽 𝑑𝑒𝑣(𝐵𝑖)
→k
J = det (F)
k = bulk modulus of the material
E = Elastomer initial elastic modulus
Bi = left Cauchy-Green tensor
𝑞(𝑡) = 𝑡/𝑇
𝑡
2𝑒 1− 𝑇
2
→ Ec
→ λ, Ef
→ λ, P, q
k = bulk modulus of the cells
Ec = initial elastic modulus of the intercellular part
λ = muscle cell pretensioning
Ef = elastic modulus of muscle fibers
P = Max contraction force per cell cross section area
q = activation level
T = time characteristic of muscle cell contraction
Modeling of bio-hybrid systems
Cell-substrate interaction and device contraction: an example
of modeling strategy
Sommario
Outline
• Il problema dell’attuazione nella
progettazione e sviluppo di macchine
• I vantaggi del muscolo naturale
• Approccio ibrido all’attuazione
• Problemi da risolvere per costruire attuatori
bioibridi usabili
• Esempi di lavori in corso
• Conclusioni e contributi da e per il tissue
engineering
Problemi da risolvere per costruire attuatori bioibridi usabili
The pieces of a bio-hybrid puzzle
Embedded
microelectrodes and
control systems
Functional interfaces
to transmit
force/power
Development of engineered
substrates
Choice of suitable cell
lines
Maximization of cell
contractility
Living / non-living interface
L. Ricotti and A. Menciassi. Bio-hybrid muscle cell-based actuators.
Biomed. Microdev. 14(6): 987-998 (2012)
Miniaturized flexible
bioreactors
Assembly of
single
contractile units
Problemi da risolvere per costruire attuatori bioibridi usabili
Choice of suitable
cell lines
• Primary mammalian cardiomyocytes (high self-beating ability)
• Primary insect dorsal vessel cells (operating at low temperatures)
• Immortalized skeletal muscle cell lines (C2C12, low differentiation)
• Primary skeletal muscle cells (need of sacrificing animals)
• Insect embryos-deriving myotubes (environmentally robust)
• Human ESCs or iPSCs (high-impact translation in regenerative
medicine)
• In any case: Co-culture of different cell types is better!
Problemi da risolvere per costruire attuatori bioibridi usabili
Maximization of cell
contractility
• Combination of chemical (growth factors) and physical stimuli
Low-serum media
Anisotropic micro/nano topographical cues
Fibroblast-deriving growth factors
Electrical stimulation
• Exogenous genetic materials insertion (miRNA)
miRNA-1 promotes myogenesis
miRNA-133 enhances myoblast proliferation
(thus hampering differentiation)
• Indirect nanoparticle-based stimuli
Responsive nanoparticles internalized by muscle cells and
stimulated by means of outer sources
J.F. Chen et al. The role
of microRNA-1 and
microRNA-133 in skeletal
muscle proliferation and
differentiation. Nature
Gen. 38: 228-233 (2005)
Problemi da risolvere per costruire attuatori bioibridi usabili
Embedded microelectrodes
and control systems
• Electrode integrability, biocompatibility and long-term stability
• Ability to avoid undesired effects (e.g. cytotoxycity, water electrolysis,
etc.)
• Control system: low level (activation
pattern) and high-level (possible
muscle synergies)
Functional interfaces to
transmit force/power
• Tendon-like structures able to connect the actuator with the external
world
• Design of active and passive mechanical features
Problemi da risolvere per costruire attuatori bioibridi usabili
Miniaturized flexible
bioreactors
• Ability to keep cells in a controlled environment
• Tuned mechanical features to not hamper actuator contraction
F. Vozzi et al. A flexible bioreactor
system for constructing in vitro
tissue and organ models.
Biotechnol Bioeng. 108(9): 21292140 (2011)
Assembly of single
contractile units
• Miniaturized or large scale actuators
• Possibility of outperforming natural solutions, in terms of shapes and
architectures, in correspondence to specific tasks
Sommario
Outline
• Il problema dell’attuazione nella
progettazione e sviluppo di macchine
• I vantaggi del muscolo naturale
• Approccio ibrido all’attuazione
• Problemi da risolvere per costruire attuatori
bioibridi usabili
• Esempi di lavori in corso
• Conclusioni e contributi da e per il tissue
engineering
Alcuni casi di studio sugli attuatori bioibridi
Choice of suitable cell
lines
Development of engineered
substrates
Maximization of cell
contractility
Indirect nanoparticle-based
stimuli
Muscle cells
Co-cultures
…
2D Matrices
3D Matrices
Alcuni casi di studio sugli attuatori bioibridi
Development of compliant substrates
Free-standing robust polymeric substrates with sub-micrometric
thickness
Poly(L-lactic acid)
T. Fujie et al. Evaluation of substrata effect on cell adhesion
properties using freestanding poly(L-lactic acid)
nanosheets. Langmuir. 27: 13173-13182 (2011)
Alcuni casi di studio sugli attuatori bioibridi
Development of compliant substrates
Low controllability
Use of a murine skeletal muscle
cell line (problems of stability
and low differentiation)
100 µm
L. Ricotti et al. Adhesion and proliferation of skeletal muscle cells on single layer
poly(lactic acid) uòtra-thin films. Biomed. Microdev. 12: 809-819 (2010)
Alcuni casi di studio sugli attuatori bioibridi
Choice of suitable cell
lines
Development of engineered
substrates
Maximization of cell
contractility
Indirect nanoparticlebased stimuli
Muscle cells
Co-cultures
…
2D Matrices
3D Matrices
Alcuni casi di studio sugli attuatori bioibridi
Development of compliant substrates
Thin free-standing polyacrylamide gels were obtained by:
• O2 plasma on glass coverslips;
• 10% acrylamide/BIS-acrylamide;
• Flat or micro-grooved Si molds;
• Detachment of molds and rinsing;
• Covalent binding of fibronectin.
Thickness:
12.2 ± 5.2 µm
Young’s modulus:
14.7 ± 1.5 kPa
Alcuni casi di studio sugli attuatori bioibridi
Anisotropic co-culture of fibroblasts and muscle cells
100 µm
Strong cell
anisotropy on µG
substrates 24 h
after seeding
100 µm
Alcuni casi di studio sugli attuatori bioibridi
Maximization of
cell contractility
Indirect
nanoparticlebased stimuli
Nanoparticles as intracellular vectors
The use of nanoparticles as drug/gene vectors is
a hot topic in nanomedicine
However, nanoparticles can be used also to indirectly convey
physical stimuli (electrical, mechanical, etc.) within cells
Alcuni casi di studio sugli attuatori bioibridi
Piezoelectric nanoparticles as intracellular vectors
BNNTs were coated with glycol
chitosan and dispersed in the
culture medium (10 µg/ml)
Direct piezoelectric
effect: internal
generation of
electrical charge
resulting from an
applied mechanical
force
US Stimulation: 20 W, 40 kHz
Alcuni casi di studio sugli attuatori bioibridi
Synergistic effects on co-cultures
Differentiation:
Day 7
25 µm
100 µm
Alcuni casi di studio sugli attuatori bioibridi
Synergistic effects on co-cultures
Electrical activity (calcium imaging) – Day 7
F
µG
L. Ricotti et al. Boron nitride nanotube-mediated stimulation of cell coculture on micro-engineered hydrogels. PLoS ONE. 8(8): e71707 (2013)
F+BNNT+US
µG+BNNT+US
Alcuni casi di studio sugli attuatori bioibridi
...
From 2D to 3D
Controlled assembly of several 2D layers
• Positioning and chemical issues
Can be approached by means of robot-assisted micromanipulation and surface functionalization strategies
Development of actual 3D constructs
• Need of 3D geometry and vascularization
Use of advanced methods for 3D scaffold fabrication
and vascularization of engineered constructs
Alcuni casi di studio sugli attuatori bioibridi
Choice of suitable cell
lines
Development of engineered
substrates
Maximization of cell
contractility
Indirect nanoparticlebased stimuli
Muscle cells
Co-cultures
…
2D Matrices
3D Matrices
Alcuni casi di studio sugli attuatori bioibridi
Three dimensional self-assembling matrices
Polydimethylsiloxane (PDMS)
Thin films by spin-assisted deposition
Different monomer / curing agent ratio (different elastic moduli)
Stress-induced rolling membrane technique
Alcuni casi di studio sugli attuatori bioibridi
Three dimensional self-assembling matrices
Polydimethylsiloxane (PDMS)
Thin films by spin-assisted deposition
Different monomer / curing agent ratio (different elastic moduli)
Stress-induced rolling membrane technique
Alcuni casi di studio sugli attuatori bioibridi
Characterization of morphology
Characterization of top layer
Characterization of bottom layer
Alcuni casi di studio sugli attuatori bioibridi
Surface chemical stability
PDMS is characterized by hydrophobic recovery
Need of a strategy for assuring long-term cell adhesion
Genipin: natural cross-linker, which assures
covalent binding of proteins to PDMS
substrates
G. Genchi et al. Bio/non-bio interfaces:
a straightforward method for obtaining long term PDMS/muscle cell
biohybrid constructs. Coll. Surf. B: Biointerf. 105: 144-151 (2013)
Stable fibronectin coating
(> 3 weeks)
Alcuni casi di studio sugli attuatori bioibridi
Three dimensional self-assembling matrices
Rolled structure (SEM imaging):
Alcuni casi di studio sugli attuatori bioibridi
Actuator contraction modeling
Finite Element Method (FEM) simulations:
• Hollow cylindrical structure (3 concentric layers);
• Yeoh’s model, 3rd order
From literature data:
• Cell dimensions and
distribution
• Forces exerted by cells:
 ~ 10 µN for each
cardiomyocyte
 ~ 1.2 µN for each
myotube
Alcuni casi di studio sugli attuatori bioibridi
Actuator contraction modeling
(Initial actuator length: 10 mm)
Achievable contractions: ~ 40%
L. Ricotti et al. Three-dimensional
tubular self-assembling structure for
bio-hybrid actuation. Proc. Conf. Liv.
Mach. (2013)
Achievable contractions: ~ 3.5%
Sommario
Outline
• Il problema dell’attuazione nella
progettazione e sviluppo di macchine
• I vantaggi del muscolo naturale
• Approccio ibrido all’attuazione
• Problemi da risolvere per costruire attuatori
bioibridi usabili
• Esempi di lavori in corso
• Conclusioni e contributi da e per il tissue
engineering
Conclusioni e contributi da e per il tissue engineering
Contributions FROM tissue engineering
Advanced
scaffolds for
skeletal muscle
tissue
engineering
Development of
engineered
substrates
Nanomaterials
and methods for
cell
engineering:
maximization of
contractility,
long-term
stability and
environmental
robustness
Choice of suitable
cell lines
Maximization of
cell contractility
Conclusioni e contributi da e per il tissue engineering
Contributions TO tissue engineering
Embedded
Miniaturized
microelectrodes and
flexible
control systems
bioreactors
Advanced
tools for
stimulation,
monitoring and
maintenance of
cell constructs
Robot-assisted
micromanipulation
systems and
advanced
assembly
strategies to
build complex
3D structures
Assembly of single
contractile units
Thank you for your
attention