Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, 610031, China.
College of Polymer Science and Engineering, Sichuan University, Chengdu, 610065, China.
Adv Healthc Mater. 2023 Sep;12(23):e2300297. doi: 10.1002/adhm.202300297. Epub 2023 May 16.
Chronic nonhealing diabetic wounds are a serious complication of diabetes, with a high morbidity rate that can cause disability or death. The long period of inflammation and dysfunctional angiogenesis are the main reasons for wound-healing difficulty in diabetes. In this study, a multifunctional double-layer microneedle (DMN) is constructed to control infection and promote angiogenesis, meeting the multiple demands of the healing process of a diabetic wound. The double-layer microneedle is consisted in a hyaluronic acid substrate and a mixture of carboxymethyl chitosan and gelatin as the tip. The antibacterial drug tetracycline hydrochloride (TH) is loaded into the substrate of the microneedle to achieve rapid sterilization and promote resistance to external bacterial infections. The microneedle tip loaded with recombinant human epidermal growth factor (rh-EGF) is inserted into the skin, in response to gelatinase produced by resident microbe and disassociate to achieve the enzymatic response release. The double-layer drug-loaded microneedles (DMN@TH/rh-EGF) have antibacterial and antioxidant effects, and promote cell migration and angiogenesis in vitro. In an in vivo diabetic wound model, using rats, the DMN@TH/rh-EGF patch is able to inhibit inflammation, promote angiogenesis, collagen deposition, and tissue regeneration during the wound healing process, promoting its healing.
慢性难愈性糖尿病创面是糖尿病的一种严重并发症，发病率高，可导致残疾或死亡。长期的炎症和功能失调的血管生成是糖尿病创面愈合困难的主要原因。在本研究中，构建了一种多功能双层微针（DMN），以控制感染和促进血管生成，满足糖尿病创面愈合过程的多种需求。双层微针由透明质酸基底和壳聚糖羧甲基混合物与明胶作为针尖组成。将抗菌药物盐酸四环素（TH）载入微针的基底中，以实现快速杀菌，并增强对外来细菌感染的抵抗力。将装载有重组人表皮生长因子（rh-EGF）的微针针尖插入皮肤，以响应常驻微生物产生的明胶酶并解离，以实现酶反应释放。双层载药微针（DMN@TH/rh-EGF）具有抗菌和抗氧化作用，并能促进细胞迁移和体外血管生成。在体内糖尿病创面模型中，利用大鼠，DMN@TH/rh-EGF 贴片能够在创面愈合过程中抑制炎症、促进血管生成、胶原沉积和组织再生，从而促进创面愈合。
