Signaling of extracellular matrices for tissue regeneration and therapeutics

Cells receive important regulatory signals from their extracellular matrix (ECM) and the physical property of the ECM regulates important cellular behaviors like cell proliferation, migration and differentiation. A large part of tissue formation and regeneration depends on cellular interaction with its ECM. A comprehensive understanding of the mechanistic biochemical pathway of the ECM components is necessary for the design of a biomaterial scaffold for tissue engineering. Depending on the type of tissue, the ECM requirement might be different and this would influence its downstream intracellular cell signaling. Here, we reviewed the ECM and its signaling pathway by discussing: 1) classification of the ECM into hard, elastic and soft tissue based on its physical properties, 2) proliferation and differentiation control of the ECM, 3) roles of membrane receptor and its intracellular regulation factor, 4) ECM remodeling via inside-out signaling. By providing a comprehensive overview of the ECM's role in mechanotransduction and the self-regulatory effect of cells back on the ECM, we hope to provide a better insight of the physical and biochemical cues from the ECM. A sound understanding on the in vivo ECM has implication on the choice of materials and surface coating of biomimetic scaffolds used for tissue regeneration and therapeutics in a cell-free scaffold.