A Human-Derived, Collagen-Rich Hydrogel Augments Wound Healing in a Diabetic Animal Model

Background Application of collagen products to wounds has been shown to improve wound healing. Using a collagen-based hydrogel (cHG) capable of cellular support previously developed by our laboratory, we hypothesize that our hydrogel will increase the speed of wound healing by providing a 3-dimensional framework for cellular support, increasing angiogenesis and cell-proliferation at the wound bed. Methods Two, 10-mm excisional wounds were created over the dorsum of 12 male, genetically modified Zucker diabetic rats. Wounds were splinted open to limit healing by wound contracture. One wound was treated with an occlusive dressing (OD), whereas the adjacent wound was treated with an OD plus cHG. Occlusive dressings were changed every other day. Hydrogel was applied on day 2 and every 4 days after until complete wound closure. Rate of wound closure was monitored with digital photography every other day. Wounds were harvested at days 10 and 16 for histological and immunohistochemical analysis. Results Wound closure was significantly faster in cHG-treated wounds compared with OD-treated wounds. By day 10, cHG-treated wounds achieved 63% wound closure, compared with 55% wound closure in OD-treated wounds ( P < 0.05). By day 16, cHG-treated wounds achieved 84% wound closure, compared with 68% wound closure in OD-treated wounds ( P < 0.05). Histologically, wound depth was not different between the cHG and OD groups on days 10 and 16. However, wound length was significantly less in the cHG group compared with the OD group ( P < 0.05) consistent with digital photographic analysis. Immunohistochemical analysis for RECA-1 demonstrated that blood vessel density in the wound bed was 2.3 times higher in the cHG group compared with the OD group ( P = 0.01) on day 16. Cell proliferation was 3.8 times higher in the cHG group versus the OD group ( P < 0.05) on day 10. Conclusions Collagen-based hydrogel–treated wounds demonstrated significantly improved healing compared with control. The thermoresponsive feature of collagen hydrogel and its structural stability at body temperature demonstrate promising clinical potential as a vehicle for the delivery of therapeutic cells to the wound bed.