Emanuele Giordano

Responsabile Lab ICM | BioEngLabDEI | CIRI SdV-TS

Università di Bologna

emanuele.giordano@unibo.ithttps://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

Parti Biologiche Standard

REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016

“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

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.

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.

REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016

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.

Parti Biologiche Standard

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

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

REYKJAVIK UNIVERSITY, FEBRUARY 22, 201646/46

REYKJAVIK UNIVERSITY, FEBRUARY 22, 2016

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

emanuele.giordano@unibo.ithttps://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