The wound environment as a regulator of fibroblast phenotype

Fibroblasts are fundamental to successful wound healing. We hypothesized that the induction and regulation of various fibroblast functions (proliferation, collagen synthesis, and remodeling) are determined by the wound environment. We examined the effect of wound fluid (WF), as a reflection of the wound environment, on the phenotypic expression of normal dermal (NF) and wound-harvested fibroblasts (WHF). WF and WHF were obtained from implanted polyvinyl alcohol sponges in 10-day-old wounds. NF and WHF were used between one and three passages. Proliferative function was assayed in a microculture system using serum stimulation (n = 12). The proliferative response of both NF and WHF to serum was significantly reduced by the addition of 20% WF (17,261 +/- 1231 cpm vs 2704 +/- 1215 cpm for NF, P less than 0.05; and 15,391 +/- 3735 cpm vs 1701 +/- 816 cpm for WHF, P less than 0.05 in serum and WF, respectively). Total protein synthesis (measured by [3H]proline incorporation) was equal in both fibroblast types; however, the relative collagen synthesis (collagenase-digestible fraction) was markedly different (2.2 +/- 0.9% for NF vs 11.4 +/- 2% for WHF, P less than 0.05). Addition of WF markedly enhanced NF collagen synthesis to 9.4 +/- 2%, but had no effect on WHF. Mechanical and remodeling functions were assayed using fibroblast-populated collagen lattices. In serum, WHF contracted the lattices faster than NF (499 +/- 14 mm2 vs 770 +/- 30 mm2 at 24 hr, P less than 0.05, and 301 +/- 18 mm2 vs 540 +/- 21 mm2 at 72 hr, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)