Regeneration mechanism for skin and peripheral nerves clarified at the organ and molecular scales

This article is a review of current research on the mechanism of regeneration of skin and peripheral nerves based on use of collagen scaffolds, particularly the dermis regeneration template (DRT), which is widely used clinically. DRT modifies the normal wound healing process, converting it from wound closure by contraction and scar formation to closure by regeneration. DRT achieves this modification by blocking wound contraction, which spontaneously leads to cancellation of scar formation, a process secondary to contraction. Contraction blocking by DRT is the result of a dramatic phenotype change in contractile cells (myofibroblasts, MFB) which follows specific binding of integrins α1β1 and α2β1 onto hexapeptide ligands, probably GFOGER and GLOGER, that are naturally present on the surface of collagen fibers in DRT. The methodology of organ regeneration based on use of DRT has been recently extended from traumatized skin to diseased skin. Successful extension of the method to other organs in which wounds heal by contraction is highly likely though not yet attempted. This regenerative paradigm is much more advanced both in basic mechanistic understanding and clinical use than methods based on tissue culture or stem cells. It is also largely free of risk and has shown decisively lower morbidity and lower cost than organ transplantation. Keywords: Regeneration, Skin, Peripheral nerves, Phenotype change, Contraction blocking, Integrin-ligand interactionNational Institutes of Health (U.S.) (RO1 NS051320)Horizon 2020 Framework Programme (European Commission) (Grant DLV-658850)National Institutes of Health (U.S.) (5-P41-EB015871-28)Singapore-MIT Alliance for Research and Technology (SMART)Hamamatsu Corporatio