The hypothesis of 'biophysical matrix contraction': wound contraction revisited.

Wound contraction is an orchestrated phenomenon that contributes to closure of wounds that heal by secondary intention. However, excessive and premature contraction results in scarring. Although the exact mechanism of contraction is unknown, the wound closure process is accompanied by and followed by changes in the physical and mechanical properties of the wound and periwound tissues during the biological transformation. Transforming growth factor-beta (TGF-beta) induces a contractile phenotype in the cellular-extracellular matrix. Meanwhile, various external and internal mechanical stresses lead to microdeformations of the wound milieu with resultant upregulation of TGF-beta. Furthermore, the mechanical strain exerted on collagen fibres and other piezoelectric tissues leads to development of piezoelectric current in the wound site, which acts synergistically with TGF-beta. TGF-beta and mechanical strain regulate the orientation of collagen fibres parallel with the skin surface, which minimises the induction of piezoelectricity through the action of internal forces because of improper angulation of collagen fibres and these forces. The resulting dominance of external forces guides the contractile activity towards restoration of the original unwounded tissue architecture and functional activity of the previously wounded milieu. The aforementioned contractile activity proceeds into the remodelling phase of wound healing as the level of TGF-beta is reduced and myofibroblasts undergo apoptosis.