Extracellular Matrix as an Inductive Scaffold for Functional Tissue Reconstruction

The extracellular matrix (ECM) is a complex network of both structural and functional proteins assembled in unique tissue-specific architectures. The ECM provides both a mechanical framework for each tissue and organ and an inductive substrate for cell signaling. The ECM is highly dynamic and cells receive signals from the ECM and contribute to its content and organization. This process of "dynamic reciprocity" is key to tissue development and for homeostasis. Based upon these important functions, ECM-based materials have been used in a wide variety of tissue engineering and regenerative medicine approaches to functional tissue reconstruction. It has been shown that ECM-based materials, when appropriately prepared, can act as facilitators of stem cell migration and macrophage phenotype modulation that promote de novo functional, site-appropriate, tissue formation. Herein, the diverse structural and functional roles of the ECM are reviewed to provide a rationale for the use of ECM scaffolds in regenerative medicine. Translational examples of ECM scaffolds are given and the potential mechanisms by which ECM scaffolds elicit constructive remodeling are discussed.