Acting as a Mechanical Stimulation to Regulate Cell Responses

In addition to the mechanical stimulations externally applied through scaffolds, the mechanical properties of scaffolds themselves, such as elasticity or stiffness, act as a mechanical stimulation as well that the attached cells can directly feel or sense [76, 77]. In order for a cell to sense the mechanical properties of the underlying substrate, the substrate should be strong enough to resist the traction force exerted by the adhered cell. Otherwise, for an extremely soft scaffold, even when the mechanical integrity is maintained under external loading, the soft scaffold cannot allow a balance to be established between the cell traction forces and the resistance of scaffolds to these forces, which is necessary for the assembly of functional cell- matrix adhesion complexes, actin cytoskeleton and cell spreading [67]. Consequently, cells are not able to form detectable cell-material adhesion complexes as well as actin cytoskeleton, and thus remain rounded, non-spread and become non-viable [78]. The cell traction force to be balanced by the scaffolds is dependent on cell lineage. Osteoblasts require higher while neurons require much lower scaffold stiffness to resist their traction force [77]. This determines the dependence of cell responses on the mechanical properties of scaffolds. Chatterjee et al. [79] investigated the effects of scaffold modulus on the mineralization of osteoblasts by fabricating a poly(ethylene glycol) hydrogel with gradient compressive modulus spanning from «10 kPa to «300 kPa. It was found that gel moduli of «225 kPa and higher enhanced osteogenesis compared to those softer gels and gel stiffness of scaffolds could be leveraged to induce cell differentiation in 3D culture as an alternative to biochemical cues such as soluble supplements, immobilized biomolecules and vectors.

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