Wound splinting modulates granulation tissue proliferation

Attachment of the extracellular matrix to a substratum is important for fibroblast survival and proliferation in three-dimensional in vitro culture systems. We hypothesized that wound matrix attachment in a wound splinting model would modulate wound cell proliferation in vivo. Male rats were excisionally wounded on the dorsum, and a splint was sutured to the wound edge. In one experiment (N=12), 6 rats were desplinted on day 5, and then all were sacrificed 24 h later, 6 h after 5-bromo-2′-deoxyuridine (BrdU) injection. In the second experiment (N=18), 6 rats each were desplinted, desplinted with wound edge release, or not disturbed, followed by BrdU injection and sacrifice 24 h later. BrdU-labeled nuclei were quantified on frozen sections of granulation tissue, cut at three different levels. In the first experiment, the percentage of BrdU-positive nuclei per high power field (hpf) in the splinted vs. desplinted animals was 6.15±2.45 (S.D.) vs. 3.03±1.58%* p<0.001, ANOVA. In the second experiment, the number of BrdU-positive per hpf was 33.1±17.4 vs. 14.5±17.1 vs. 10.2±9.1* (splinted vs. desplinted vs. desplinted/released);*p<0.001 [analysis of variance (ANOVA)]. Removal of the wound splint decreased the rate of BrdU-labeled cells in the granulation tissue by ∼50%; complete disruption of wound matrix attachment may have decreased this rate even further. Wound cell proliferation is modulated by lateral attachment of the wound matrix.