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Purpose. Fibroblast survival within an in vitro collagen matrix is dependent on matrix anchorage to a rigid substratum. The purpose of this study was to determine whether granulation tissue survival in vivo also is dependent on matrix anchorage. We hypothesized that splinting an excisional wound (i.e., anchoring the wound edges) would promote granulation tissue survival and that desplinting a splinted wound would produce granulation tissue apoptosis.Methods. Eighteen Wistar rats (3 months, 350 g) underwent excisional wounding (2 × 2 cm, dorsal skin) with immediate wound splinting (a metal template affixed with sutures) on day 0. On day 6, rats (n = 6 per group) underwent splint removal (desplinted), splint removal with circumferential incision of the wound edge (desplint/release), or no intervention (splinted); sacrifice of all animals was on day 7. Frozen sections of granulation tissue were stained with TUNEL or H&E; data were analyzed with ANOVA and the unpaired t test.Results. The cross-sectional and surface area of the desplinted and desplint/release granulation tissue both decreased compared to the splinted granulation tissue (&ast;P < 0.05). The nuclear density of the desplint/release granulation tissue was 25% less compared to the splinted granulation tissue (&ast;P < 0.05). The desplinted and desplint/release apoptotic rates were twice and >10× greater than the splinted apoptotic rate, respectively (&ast;P < 0.05).Conclusions. The rate of cell death in a splinted wound (an in vivo equivalent of an anchored FPCM) is minimal to nil, which is consistent with our hypothesis. Desplinting and releasing the wound edge of a previously splinted wound (the in vivo equivalent of a detached FPCM) results in granulation tissue regression and a large increase in apoptosis. Desplinting a wound alone results in changes somewhat intermediate to the splinted and desplint/release conditions. Loss of wound anchorage acutely promotes granulation tissue apoptosis. [Copyright &y& Elsevier]