Statement of Purpose: Skin wounds are now considered as one of the major threats to public health and the economy. Based on understanding of the mechanisms of wound healing, numerous therapeutic methods have been developed to promote accelerated wound healing, including slow-release hydrogels for small molecules or growth factors delivery. In this study, we applied the viral immunomodulatory protein Serp-1, a serine proteinase inhibitor (serpin), to promote accelerated wound healing. Serp-1 is a purified, secreted 55kDa glycoprotein derived from Myxomavirus that interferes with the inflammation processes of its host, the European rabbit (Oryctolagus cuniculus) . Our systematic studies on Serp-1 protein demonstrate highly potent anti-inflammatory functions in a wide range of animal models of vascular disease and transplant. Serp-1 also significantly reduced markers of heart damage in a small Phase 2 clinical trial. Serp-1 proved safe in animal models and in Phase I and Phase 2a clinical trials in humans . We examined local delivery of Serp-1 in a hydrogel and assessed wound healing with topical Serp-1 treatment. Topical delivery methods for Serp-1 wound treatments were compared to determine the optimal application approach.