Distilling complexity to advance regenerative medicine from laboratory animals to humans, in situ regeneration will continue to evolve using biomaterial strategies to drive endogenous cells within the human body for therapeutic purposes; this approach avoids the need for delivering ex vivo-expanded cellular materials. Ensuring the recruitment of a significant number of reparative cells from an endogenous source to the site of interest is the first step toward achieving success. Subsequently, making the "cell home" cell-friendly by recapitulating the natural extracellular matrix (ECM) in terms of its chemistry, structure, dynamics, and function, and targeting specific aspects of the native stem cell niche (e.g., cell-ECM and cell-cell interactions) to program and steer the fates of those recruited stem cells play equally crucial roles in yielding a therapeutically regenerative solution. This review addresses the key aspects of material-guided cell homing and the engineering of novel biomaterials with desirable ECM composition, surface topography, biochemistry, and mechanical properties that can present both biochemical and physical cues required for in situ tissue regeneration. This growing body of knowledge will likely become a design basis for the development of regenerative biomaterials for, but not limited to, future in situ tissue engineering and regeneration.
Keywords: biomimetic design; cell migration; endogenous regeneration; matrix biology; stem cell niches.
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