Biological scaffolds for regenerative medicine

The ideal biological scaffold would provide structural support appropriate for the tissue of interest, and an adhesion surface that maintains phenotypic cues suited to the tissue and has the ability to change as the functional requirements of the target tissue change. The extracellular matrix (ECM) is the aggregate product of cells that reside in a given tissue, organ, or microenvironment and has all of these characteristics. In addition to serving as structural support for the tissue, the ECM has numerous functional roles that it fulfills through site-specific ligands that serve as cell-attachment anchors, differentiation cues, and mediators of intracellular signaling pathways. Furthermore, the ECM is in a constant state of “dynamic reciprocity” with the resident cells of the given tissues or organ, which is manifested by the temporal change in composition and structure in response to the requirements and activity of the resident cells that reside within the ECM. Stated differently, the composition and structure of the matrix are optimized for each tissue and change in response to mechanical forces, biochemical milieu, oxygen requirements/concentration, pH, and gene expression, among other factors. The ECM also plays a central role in mammalian development, normal physiology, and the response to injury. For these reasons, if harvested and processed appropriately, the ECM has been shown to promote constructive, site-specific remodeling when used as a biological scaffold for regenerative medicine applications. Beginning with a discussion of the components that comprise the extracellular matrix, the present chapter will review the use of extracellular matrix as a biological scaffold material in tissue engineering and regenerative medicine applications with a specific focus on the mechanisms by which such scaffolds promote functional restoration of tissue following injury.