Active biomaterials/scaffolds for stem cell-based soft ... · PDF fileParti Biologiche...
Transcript of Active biomaterials/scaffolds for stem cell-based soft ... · PDF fileParti Biologiche...
Emanuele Giordano
Responsabile Lab ICM | BioEngLabDEI | CIRI SdV-TS
Università di Bologna
[email protected]://www.unibo.it/sitoweb/emanuele.giordano/en
Active biomaterials/scaffolds for stem cell-based soft tissue engineering
(in a nutshell…)
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
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“He bound devious Prometheus withinescapable harsh bonds, fastenedthrough the middle of a column, and heinflicted on him a long-winged eagle,which ate his immortal liver, but it grew asmuch in all at night as the long-wingedbird would eat all day.”
Θεογονία (Theogonía);Hesiod (8th – 7th century BC) describing the origins andgenealogies of the Greek gods.
Organ regeneration
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
The promise of stem cell research
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
The promise of stem cell research
May we obtain complex SCs differentiation by growing them in 2Dpolypropylene culture plates, even in presence of appropriatebiochemical cues?
A rhetorical question is a figure of speech in the form of a question that is asked to make a point ratherthan to elicit an answer…
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Substrate stiffness directs stem cell differentiation
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Mechano-sensitive pathways convert biophysical cuesinto biochemical signals that commit the cell to aspecific lineage
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Engineering stem cell microenvironment will benefittheir proliferation and differentiation into cells of interestfor biomedical and clinical applications
A variety of materials have
been developed to
match the diverse
elasticity of tissues in vivo.
Softer Harder
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Engineering stem cell microenvironment will benefittheir proliferation and differentiation into cells of interestfor biomedical and clinical applications
A variety of materials have
been developed to
match the diverse
elasticity of tissues in vivo.
Artificial biopolymers presently usedin tissue engineering are extremelystiff. As an example, polylactic acid(PLA), which is FDA-approved forimplant into humans, has a bulkelasticity of E ~ 1 GPa.
Thus engineering of soft tissuereplacements needs to explorebiopolymers softer than thosepresently available.
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Introduction of etheroatoms along the polymeric chain of aliphaticpolyesters allows to modulate the ability to crystallize of the resultingpolymers, and, above all, to enhance their flexibility and surfacehydrophilicity.
Gualandi C. et al., Soft Matter, 2012, 8, 5466–5476.Gigli M. et al., Green Chem., 2012, 14, 2885–2893.Gigli M. et al., React. Funct. Polym., 2012, 72, 303–310.Gigli M. et al., React. Funct. Polym., 2013, 73, 764–771.Gigli M. et al., Polym. Degrad. Stab., 2013, 98, 934–942.Gigli M. et al., Ind. Eng. Chem. Res., 2013, 52, 12876–12886.
How to engineering biopolymers softer than thosepresently available? A material-based approach…
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Multiblock co-polymerization of aliphatic polyesters, where differentblock lengths allows to modulate the ability to crystallize of the resultingpolymers, and, above all, to enhance their flexibility and surfacehydrophilicity.
Block length controls the polymer crystallinity, the thermal andmechanical properties, the wettability and the degradation rate. Thecopolymers display different stiffnesses, mainly depending on thecrystallinity degree and macromolecular chain flexibility, a tunable rangeof degradation rates, and different surface hydrophilicity.
How to engineering biopolymers softer than thosepresently available? A material-based approach…
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Biocompatibility assays:
- showed the absence of potentially cytotoxic products released into the culture medium by
the investigated samples.
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Biocompatibility assays:
- demonstrated that substrates support a
physical environment where cells can adhere
and proliferate.
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Biocompatibility assays:
- demonstrated that substrates offer
aphysical environment where cells can receive
definite biophysical cues.
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Native extracellular matrix (ECM) presents variousgeometrically defined physical boundaries, such asfibers that support cells and regulate their function.
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Emerging micro- and/or nano-scale engineering technologies offerunprecedented opportunities for the creation of cell microenvironment invitro that recapitulates some crucial cues in vivo, such as:
- surface topography,- dynamic mechanical microenvironment,- spatiotemporal chemical gradients,- 3D environment.
Here summarized three examples of strategies that have been used tothese aims.
How to engineering biopolymers closer to nativeextracellular matrix than those presently available?A micro/nano fabrication-based approach…
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Emerging micro- and/or nano-scale engineering technologies offerunprecedented opportunities for the creation of cell microenvironment invitro that recapitulates some crucial cues in vivo, such as:
- surface topography ,- dynamic mechanical microenvironment,- spatiotemporal chemical gradients,- 3D environment.
How to engineering biopolymers closer to nativeextracellular matrix than those presently available?A micro/nano fabrication-based approach…
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Emerging micro- and/or nano-scale engineering technologies offerunprecedented opportunities for the creation of cell microenvironment invitro that recapitulates some crucial cues in vivo, such as:
- surface topography,
- dynamic mechanical microenvironment ,- spatiotemporal chemical gradients,- 3D environment.
How to engineering biopolymers closer to nativeextracellular matrix than those presently available?A micro/nano fabrication-based approach…
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Emerging micro- and/or nano-scale engineering technologies offerunprecedented opportunities for the creation of cell microenvironment invitro that recapitulates some crucial cues in vivo, such as:
- surface topography,- dynamic mechanical microenvironment,
- spatiotemporal chemical gradients ,- 3D environment.
How to engineering biopolymers closer to nativeextracellular matrix than those presently available?A micro/nano fabrication-based approach…
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Emerging micro- and/or nano-scale engineering technologies offerunprecedented opportunities for the creation of cell microenvironment invitro that recapitulates some crucial cues in vivo, such as:
- surface topography,- dynamic mechanical microenvironment,- spatiotemporal chemical gradients,
- 3D environment .
How to engineering biopolymers closer to nativeextracellular matrix than those presently available?A micro/nano fabrication-based approach…
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Native extracellular matrix (ECM) presents variousgeometrically defined physical boundaries, such asfibers that support cells and regulate their function.
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Mechanical forces play significant developmental roles in native and engineered tissues.
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REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
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REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Parti Biologiche Standard
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Parti Biologiche Standard
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Parti Biologiche Standard
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Mandatory specifications for tissue engineering templates
The material should be capable of recapitulating the architecture of the niche of the target c ells . Sincethe cell niche is changeable over time, the material should be capable of adapting to the constantly changingmicroenvironment.
The material should have elastic properties, particularly stiffness, which favor m echanical signaling tothe target cells , to optimize differentiation, proliferation, and gene expression.
The material should have optimal surface or interfacial energy characteristics to facilitate cell adhesionand function.
The material should be capable of orchestrating molecular signaling to the target cells , either bydirecting endogenous molecules or delivering exogenous molecules.
The material should be of a physical form that provides the appropriate shape and size to theregenerated tissue .
The material should be capable of forming into an architecture that optimizes cell, nutrient, gas, andbiomolecule transport , either ex vivo or in vivo or both, and facilitates blood vessel and nervedevelopment.45/46
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REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Giovanna Della Porta
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016
Marco Govoni
Emanuele Giordano
Lab ICM | BioEngLabDEI | CIRI SdV-TS
Università di Bologna
[email protected]://www.unibo.it/sitoweb/emanuele.giordano/en
Active biomaterials/scaffolds for stem cell-based soft tissue engineering
(in a nutshell…)
REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016