组织工程皮肤在糖尿病皮肤溃疡模型大鼠创面修复中的应用研究

Application of tissue-engineered skin for wound repair in a rat model of diabetic skin ulcer

目的:探讨组织工程皮肤修复糖尿病大鼠溃疡模型创面的可能机制。方法:选择腹腔注射链脲佐菌素及背部打孔建立糖尿病溃疡模型,将60只模型大鼠随机分为5组,每组各12只,对照组采用凡士林纱布覆盖创面,支架组采用无细胞纤维蛋白支架行创面移植,成纤维细胞组采用含成纤维细胞的纤维蛋白支架行创面移植,表皮干细胞组采用含表皮干细胞的纤维蛋白支架行创面移植,组织工程皮肤组采用含成纤维细胞和表皮干细胞的纤维蛋白支架行创面移植。术后第2周和第4周,比较各组创面愈合率、炎性因子[白细胞介素(IL-1)-1、IL-2、肿瘤坏死因子(TNF)-α]和相关生长因子[血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)、转化生长因子(TGF)-β1]的含量。结果:术后第2周和第4周,组织工程皮肤组创面愈合率>成纤维细胞组(表皮干细胞组)>支架组>对照组(P<0.05);IL-1、IL-2和TNF-α含量为组织工程皮肤组<成纤维细胞组(表皮干细胞组)<支架组<对照组(P<0.05);VEGF、bFGF和TGF-β1含量为组织工程皮肤组>成纤维细胞组(表皮干细胞组)>支架组>对照组(P<0.05);与其他组相比,组织工程皮肤组大鼠创面新生皮肤质地和韧性良好,皮肤形态成熟,可见胶原纤维成束状排列。结论:组织工程皮肤能够促进糖尿病溃疡大鼠模型创面愈合,可能与拮抗创面炎症损伤、促进相关血管生长因子分泌有关。

Objective:To study the repairing mechanisms of tissue-engineered skin in a rat model of diabetic ulcer.Methods:A total of 60 diabetic ulcer rats were randomly divided into 5 groups(12 rats per group):control group(covered by Vaseline gauze),cell-free scaffold group(transplanted with cell-free fibrin scaffolds),fibroblast scaffold group(transplanted with fibrin scaffolds containing fibroblasts),epidermal stem cell scaffold group(transplanted with fibrin scaffolds containing epidermal stem cells),tissue-engineered skin group(transplanted with fibroin scaffolds containing fibroblasts and epidermal stem cells).At 2 and 4 weeks after surgery,wound healing rate,inflammatory factors(IL-1,IL-2,TNF-α),related growth factors(VEGF,bFGF,TGF-β1)were compared.Results:At 2 and 4 weeks after surgery,the wound healing rate in the tissue-engineered skin group was larger than that in the fibroblast scaffold group,followed by the epidermal stem cell scaffold,cell-free scaffold group,and control group(P<0.05).The levels of VEGF,bFGF,TGF-β1 showed a similar trend and those of IL-1,IL-2,TNF-αtook on a decreasing trend over these five groups(all P<0.05).The HE staining results showed that compared with other groups,the tissue-engineered skin group showed good texture and toughness of newly formed skin on the wound surface,mature skin morphology,and collagen fibers arranged in bundles.Conclusion:Tissue-engineered skin can promote wound healing from diabetic ulcer in model rats,which may be related to antagonizing wound inflammation and upregulating vascular growth factors.