Williams Tokoya, Sotelo Leon Daniel, Kaizawa Yukitoshi, Wang Zhen, Leyden Jacinta, Chang James, Fox Paige M
From the Division of Plastic and Reconstructive Surgery, School of Medicine, Stanford University, Stanford.
Ann Plast Surg. 2020 Sep;85(3):290-294. doi: 10.1097/SAP.0000000000002380.
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.
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.
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.
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.
已证明将胶原蛋白产品应用于伤口可促进伤口愈合。利用我们实验室先前开发的一种能够支持细胞的基于胶原蛋白的水凝胶（cHG），我们推测我们的水凝胶将通过为细胞支持提供三维框架、增加伤口床的血管生成和细胞增殖来提高伤口愈合速度。
在12只雄性转基因Zucker糖尿病大鼠的背部制造两个10毫米的切除伤口。伤口用夹板撑开以限制伤口收缩愈合。一个伤口用封闭敷料（OD）治疗，而相邻伤口用OD加cHG治疗。封闭敷料每隔一天更换一次。在第2天和之后每4天应用水凝胶，直至伤口完全闭合。每隔一天用数码摄影监测伤口闭合率。在第10天和第16天采集伤口进行组织学和免疫组织化学分析。
与OD治疗的伤口相比，cHG治疗的伤口愈合明显更快。到第10天，cHG治疗的伤口实现了63%的伤口闭合，而OD治疗的伤口为55%（P<0.05）。到第16天，cHG治疗的伤口实现了84%的伤口闭合，而OD治疗的伤口为68%（P<0.05）。组织学上，在第10天和第16天，cHG组和OD组的伤口深度没有差异。然而，与OD组相比，cHG组的伤口长度明显更短（P<0.05），这与数码摄影分析一致。对RECA-1的免疫组织化学分析表明，在第16天，cHG组伤口床的血管密度比OD组高2.3倍（P = 0.01）。在第10天，cHG组的细胞增殖比OD组高3.8倍（P<0.05）。
与对照组相比，基于胶原蛋白的水凝胶治疗的伤口愈合明显改善。胶原蛋白水凝胶的热响应特性及其在体温下的结构稳定性显示出作为向伤口床递送治疗细胞的载体具有广阔的临床潜力。
