PURPOSE: Developing new therapies to promote wound healing and mitigate scarring has the potential to significantly impact patient morbidity, particularly for those who suffer from chronic non-healing wounds and burns. The primary objectives for any therapy that aims to improve wound healing are to provide protection against external factors and to sustain optimal moisture levels within the wound bed. Biologic scaffolds such as hydrogels provide an ideal, physio-mimetic of native ECM that can improve wound healing outcomes after cutaneous injury. While most studies have focused on the benefits of hydrogels in accelerating wound healing, there is minimal data directly comparing the relative efficacies among different hydrogel material compositions. METHODS: In this study we utilized a splinted excisional wound model that recapitulates human-like wound healing in mice, and treated wounds with three different collagen hydrogel dressings. The first dressing was composed of 90% collagen and 10% alginate. The second dressing was composed of 55% collagen and 44% cellulose. Finally, the third dressing was composed of 5% collagen and 95% pullulan. We assessed the feasibility of applying each dressing during standard dressing changes and measured wound areas over time to determine the relative rate of wound closure. We then performed histologic and histopathologic analysis on the explanted scar tissues to assess the effects each hydrogel dressing on collagen architecture, fiber alignment, and cellular response. RESULTS: The days to closure of wounds treated the collagen-pullulan hydrogel (~11.2 days) was significantly shorter than the collagen-cellulose treated (~13.2 days; *p<0.05) and control (~13.8 days; *p<0.01) wounds. Quantitative analysis of collagen architecture demonstrated that collagen-pullulan treated wounds had a lower proportion of mature collagen within the healed scar and significantly more randomly aligned collagen fibers compared to collagen-cellulose treated wounds. Furthermore, we found that collagen-pullulan hydrogel treated wounds displayed significantly shorter fiber length and greater tissue porosity compared to the other wound groups. Finally, histopathologic analysis revealed lower levels of immune cell infiltration and overall tissue response in collagen-pullulan hydrogel treated wounds relative to other groups. CONCLUSION: Our data indicate that the material composition of hydrogel dressings can significantly influence healing time, cellular response, and the resulting architecture of healed scars. Collagen-pullulan hydrogel therapy accelerated wound closure and promoted tissue with less dense, more randomly aligned, and shorter collagen fibers with lower collagen intensity, similar to the natural ‘basket-weave’ architecture of unwounded skin. Further understanding of how specific hydrogel properties affect healing and the resulting tissue architecture of wounds may lead to novel insights and further optimization of the material properties of wound dressings.
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