Collagen-based Hydrogel Accelerates Wound Healing in Diabetic Rats
Tokoya Williams, MD, Daniel Leon, BS, Yukitoshi Kaizawa, MD, PhD, James Chang, MD, Paige Fox, MD, PhD.
Stanford University, Palo Alto, CA, USA.
PURPOSE: Wound care constitutes a significant monetary burden on society with estimated costs of over 25 billion dollars annually. Equally significant are the related costs to patients, including pain, multiple doctorsí visits, the need for assistance with wound care, restricted social interactions, and time lost from work. Technology to enhance and expedite wound healing would be valuable. The goal of this project is to improve wound healing using a collagen-based tendon hydrogel, which provides a three-dimensional framework for wound healing. We hypothesize that the rate of wound healing will be superior in wounds treated with tendon hydrogel (tHG) vs. traditional wound care.
A splinted excisional wound model in genetically modified diabetic rats was utilized. Briefly, two, 10 mm wounds were evenly space over the ratsí dorsum at the level of the forelimb. Wounds were splinted open to limit the role of wound contracture in healing. On each rat, one wound was treated with an occlusive dressing (OD) while the other wound was treated with an occlusive dressing plus tHG. Dressings were changed every other day until complete wound closure. Rate of wound closure was monitored with digital photographs taken every other day. Image J software (NIH, public domain) was used to analyze wound size. Wound closure was defined as percentage closure of the wound bed compared to initial wound size. To examine wound architecture, wounds were harvested at days 10 and 16. Hematoxylin and Eosin (H&E) was used to assess wound length and depth using image J software. Immunohistochemistry (IHC) was used to evaluate neovascularization (RECA) and cell proliferation (Ki-67). Image J was used for objective assessment of IHC images. Significant differences in rate of wound closure, wound depth, vascularity, and cell proliferation were calculated using the Studentís T-Test.
Wound closure was significantly faster in tHG treated wound compared to OD treated wounds. By day 10, tHG treated wounds achieved 63% wound closure, compared to 55% wound closure in OD only wounds (p<0.05). By day 16, tHG treated wounds achieved 84% wound closure, compared to 68% wound closure in OD only wounds (p<0.05). Histologically, wound depth was not different between the tHG and OD groups. However, wound length was significantly less in the tHG group compared to the OD group (p<0.05) consistent with digital photographic analysis. IHC at day 10 showed no significant difference in blood vessel density between the tHG and OD (p=0.75). However, cell proliferation in the wound bed was 3.8 times higher in the tHG group versus the OD group (p<0.05).
Tendon derived hydrogel treated wounds demonstrated significantly accelerated healing and increased cell proliferation compared to wounds treated with an occlusive dressing. These findings are promising for the use of tHG as a simple topical agent to accelerate wound healing. Future studies will assess the role of hydrogel reseeding to further augment wound healing.
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