The long-term objective of this research is to develop tunable collagen-based biomaterial scaffolds for directed stem cell differentiation into neural lineages to aid in CNS diseases and trauma. Type I collagen is a ubiquitous protein that provides mechanostructural and ligand-induced biochemical cues to cells that attach to the protein via integrin receptors. Previous studies have demonstrated that the mechanical properties of a substrate or tissue can be an important regulator of stem cell differentiation. For example, the mechanical properties polyacrylamide gels can be tuned to induce neural differentiation from stem cells [1, 2]. Mesenchymal stem cells (MSCs) cultured on ployacrylamide gels with low elastic modulus (0.1–1 kPa) resulted in a neural like population. MSCs on 10-fold stiffer matrices that mimic striated muscle elasticity (Emuscle ∼8–17 kPa) lead to spindle-shaped cells similar in shape to myoblasts. Still stiffer gels (25–40 kPa) resulted in osetoblast differentiation. Based on these observations, collagen gels may provide an ideal material for differentiation into neural lineages because of their low compliance.

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