Modulatory activities of wound fluid on fibroblast proliferation and collagen synthesis

Several different cell types play a role in the regulatory mechanisms involved in wound healing. A rat wound model was used to evaluate temporal changes in the cellular infiltrate, histology, and effects of wound fluid (WF) on fibroblast growth and collagen synthesis in vitro. Polyvinyl alcohol sponges were implanted in male Sprague/Dawley rats and harvested after 1, 3, 5, 7, 10, and 15 days. Rat wound fibroblasts were cultured in different media with 10 or 20% WF pooled from five or more rats from each time interval, and then pulsed with [3H]thymidine. Days 1 through 5 WF stimulated proliferation, whereas Days 10 and 15 WF inhibited proliferation. Stimulatory activity was found in the greater than 300 kDa molecular weight fraction; inhibitory activity was in the less than 10 kDa molecular weight fraction. Ten percent WF from both Day 1 and Day 15 sponges exerted a stimulatory effect in incubated fibroblasts on collagen production, measured as protein-bound [3H]hydroxyproline. Fibroblast proliferation and collagen synthesis appeared to be independently regulated functions. Fibroblasts were stimulated by the wound environment to proliferate for about 1 week after injury, at which point further growth was inhibited, while collagen production was maintained.