Role of growth factors in scar contraction: an in vitro analysis

Excessive scar contracture by wound fibroblasts can have devastating consequences, ranging from body disfigurement to joint immobility. The ability of fibroblasts isolated from lesions of hypertrophic scars, keloids, normal skin, or normal scars in contracting the provisional wound matrix (i.e., fibrin clot) was compared and analyzed. Hypertrophic scar fibroblasts showed a consistently higher basal level of fibrin matrix gel (FMG) contraction than other fibroblasts. This heightened basal level of contractility may be attributed partially to the autocrine effect of transforming growth factor-beta 1 (TGF-beta 1). Normal and keloid fibroblasts exhibited similar basal rates of FMG contraction, and both responded to platelet-derived growth factor (PDGF) and TGF-beta by increasing FMG contraction two- to threefold. However, 45% of the TGF-beta-induced increase in FMG contraction by keloid fibroblasts, but not normal fibroblasts, was mediated by the autocrine production of PDGF. Therefore, fibroblasts isolated from different scars exhibit varied degrees of FMG contraction. In addition, the mechanism underlying growth factor-mediated contraction differed vastly among fibroblasts of different scar origin. The significance of these differences in growth factor-mediated FMG contraction is discussed.