Skin wound healing and scarring: fetal wounds and regenerative restitution

Abstract

The adverse physiological and psychological effects of scars formation after healing of wounds are broad and a major medical problem for patients. In utero, fetal wounds heal in a regenerative manner, though the mechanisms are unknown. Differences in fetal scarless regeneration and adult repair can provide key insight into reduction of scarring therapy. Understanding the cellular and extracellular matrix alterations in excessive adult scarring in comparison to fetal scarless healing may have important implications. Herein, we propose that matrix can be controlled via cellular therapy to resemble a fetal-like matrix that will result in reduced scarring.

Keywords: CXCR3; ECM; fetal wounds; fibrosis.

Figure 1

CXCR3 “stop” signals in scar prevention. CXCR3 receptor is a seven transmembrane G protein coupled receptor. In human and rodent, the receptor is ubiquitous, but the ligands are regulated temporally and spatially. CXCR3 receptor is expressed on keratinocytes, fibroblast, and endothelial cells. Its ligands are CXCL10/IP-10 that appears in the dermis and is produced by endothelial cells of the neovasculature and CXCL11/IP-9 is expressed in redifferentiating keratinocytes behind the leading edge of the wound. Signaling through CXCR3 blocks growth factor-induced motility of fibro-blasts and endothelial cells by suppressing m-calpain activation. In contrast, this signaling promotes keratinocytes motility and more rapid re-epithelialization. In the absence of ‘stop’ signals of CXCR3, fibroplasia results in an immature matrix which in turn recruits more inflammatory cells that stimulate the stromal cells to produce more regenerative matrix. This drives scarring.