Figure 3. Survival and fate of peripheral cell types as a function of biomaterial stiffness.

This is a general summary of results obtained across a variety of biomaterials, therefore it is important to remember that biomaterial composition can also have an effect on cell survival and proliferation. (A) Chondrocytes appear to grow on a broad range of stiffnesses, however, the differential expression of collagens and ECM components (ie. aggrecan, glycosaminoglycans) could be a function of the stiffness of the biomaterial (Bryant and Anseth, 2002; Nettles et al., 2004; Chung et al., 2006; Lin et al., 2011; Nguyen et al., 2011). (B) Based on available information, fibroblasts may need a less stiff biomaterial for survival and proliferation, compared to studies that have used chondrocytes (Shu et al., 2004; Burdick et al., 2005; Shu et al., 2006). Based on two in vivo studies, encapsulated fibroblasts inserted subcutaneously survive and produce ECM components in biomaterials with both softer and stiffer characteristics (Shu et al., 2004; Shu et al., 2006). (C) Mesenchymal stem cells (MSC) also appear to survive and proliferate better on softer materials, however, changes in stiffness alters the MSC differentiation. In softer materials, MSC begin to express neuronal markers. As the stiffness increases, MSC may begin to express adipogenic or myogenic markers in addition to increasing their expression of factors important to angiogenesis (i.e. VEGF). At the higher range of stiffness, MSC express osteogenic markers (Engler et al., 2006; Chung et al., 2009; Chung and Burdick, 2009; Seib et al., 2009; Huebsch et al., 2010; Quinchia Johnson et al., 2010; Jha et al., 2011).