Ding Zhaozhao, Zhang Yunhua, Guo Peng, Duan Tianbi, Cheng Weinan, Guo Yang, Zheng Xin, Lu Guozhong, Lu Qiang, Kaplan David L
National Engineering Laboratory for Modern Silk & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, P. R. China.
Department of Burns and Plastic Surgery, The Affiliated Hospital of Jiangnan University, Wuxi 214041, P. R. China.
ACS Biomater Sci Eng. 2021 Mar 8;7(3):1147-1158. doi: 10.1021/acsbiomaterials.0c01502. Epub 2021 Feb 1.
Dysangiogenesis and chronic inflammation are two critical reasons for diabetic foot ulcers. Desferrioxamine (DFO) was used clinically in the treatment of diabetic foot ulcers by repeated injections because of its capacity to induce vascularization. Biocompatible carriers that release DFO slowly and facilitate healing simultaneously are preferable options to accelerate the healing of diabetic wounds. Here, DFO-laden silk nanofiber hydrogels that provided a sustained release of DFO for more than 40 days were used to treat diabetic wounds. The DFO-laden hydrogels stimulated the healing of diabetic wounds. In vitro cell studies revealed that the DFO-laden hydrogels modulated the migration and gene expression of endothelial cells, and they also tuned the inflammation behavior of macrophages. These results were confirmed in an in vivo diabetic wound model. The DFO-laden hydrogels alleviated dysangiogenesis and chronic inflammation in the diabetic wounds, resulting in a more rapid wound healing and increased collagen deposition. Both in vitro and in vivo studies suggested potential clinical applications of these DFO-laden hydrogels in the treatment of diabetic ulcers.
血管生成异常和慢性炎症是糖尿病足溃疡的两个关键原因。去铁胺（DFO）因其诱导血管生成的能力而在临床上用于通过反复注射治疗糖尿病足溃疡。能够缓慢释放DFO并同时促进愈合的生物相容性载体是加速糖尿病伤口愈合的更佳选择。在此，使用了能持续释放DFO超过40天的载有DFO的丝纳米纤维水凝胶来治疗糖尿病伤口。载有DFO的水凝胶刺激了糖尿病伤口的愈合。体外细胞研究表明，载有DFO的水凝胶调节了内皮细胞的迁移和基因表达，并且还调节了巨噬细胞的炎症行为。这些结果在体内糖尿病伤口模型中得到了证实。载有DFO的水凝胶减轻了糖尿病伤口中的血管生成异常和慢性炎症，从而使伤口愈合更快且胶原沉积增加。体外和体内研究均表明这些载有DFO的水凝胶在治疗糖尿病溃疡方面具有潜在的临床应用价值。
