Page 107 - Tailoring Electrospinning Techniques for Regenerative Medicine - Marc Simonet

structure (i.e. fiber diameter and morphology, fiber interconnections and mutual organization) and local mechanical stresses and strains. While many of these ECM related properties might be incorporated in sca olds for heart valve tissue engineering, stresses and strains cannot. The sca old material should, however, be designed to facilitate the application of such loads, for instance by providing elastic environments that allow for ongoing cyclic loading of the cells and neo tissue.
Cell adhesion plays a crucial role in regulating cell motility, proliferation and di erentiation. Since the identification of the RGD tripeptide of fibronectin and other adhesion molecules,40 several approaches to reconstitute the cell-adhesive character of the ECM in three-dimensional sca olds have been developed. For cardiovascular tissue engineering Arg-Glu-Asp-Val (REDV) and Val-Ala-Pro-Gly (VAPG) peptide sequences have been used to selectively capture endothelial cells and smooth muscle cells in heterogeneous cell suspensions under shear stress.41 Whereas overall cell adhesion in these studies was dominated by the shear stress, the selective adhesion could be better controlled by the type of peptide. Apart from the type of peptides, the surface density and spatial distribution of peptides can be used to control cell fate.42 In addition to synthetic materials, it is further possible to incorporate cell adhesion ligands into biologically derived materials to alter their adhesive character. This has been explored for
decellularized heart valves in an attempt to improve the cell adhesive properties of these sca olds.43
The micro-mechanical environment of the
cell is another important regulator of cell function
and viability, either through the application of
external mechanical loads to cells, or through the development of cell contractile forces on materials
with di erent mechanical properties. 2D cell culture
studies on substrates with varying elastic moduli have demonstrated that (stem) cell di erentiation can be
influenced by the mechanical properties of the cell’s microenvironment.44,45 The ability to reproduce these
properties in a synthetic 3D sca old may provide a
potent means of controlling cell fate both in-vitro
and in-situ. Kloxin et al. used a photodegradable
hydrogel to study the e ects of a wide range of elastic 5 moduli on the di erentiation of porcine valvular
interstitial cells (VICs) into myofibroblasts.46 VICs
cultured on high moduli di erentiated into matrix
producing myofibroblasts, whereas decreasing the
substrate modulus suppressed this di erentiation, demonstrating that myofibroblasts can be de- di erentiated solely by changing the modulus of the
underlying substrate. These findings are important
for the rational design of biomaterials for heart valve regeneration and o er insight into fibrotic tissue development and counteractive therapy by changing
the microenvironment elasticity.
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