The healing of diabetic foot ulcers (DFUs) is a major challenge for clinical treatment because of the hyperglycemic and acidic microenvironment in the wound area. In this study, a self-healing, injectable, and pH-responsive hydrogel was synthesized by N-carboxyethyl chitosan (N-chitosan), hyaluronic acid–aldehyde (HA-ALD), adipic acid dihydrazide (ADH) through the formation of the reversible dynamic bonds, acylhydrazone and imine bonds. The presence of the acylhydrazone bond characterizes the hydrogel pH-responsive property. In this study, the insulin glargine was successfully incorporated into the hydrogel, allowing its sustained and pH-responsive releasing from the hydrogel for up to 14 days. The hydrogel presented good compatibility and pore structure, and the insulin released from the hydrogel maintained its original bioactivity. Full thickness wounds were established on the feet of diabetic rats to evaluate the therapeutic effect of the dressing. The results revealed that the bioactive insulin-loaded hydrogel dressing shortened the inflammatory phase, enhanced granulation tissue formation, promoted collagen deposition, accelerated re-epithelialization and neovascularization, and postponed or even improved peripheral neuropathy, thus, significantly accelerated DFUs healing. Our findings showed that the insulin-loaded hydrogels had promising potential as a multifunctional bioactive wound dressing for enhancing DFUs healing.

由于伤口区域的高血糖和酸性微环境，糖尿病足溃疡（DFU）的愈合是临床治疗的主要挑战。在这项研究中，由 N-羧乙基壳聚糖（N-壳聚糖）、透明质酸 - 醛（HA-ALD）、己二酸二酰肼（ADH）通过形成可逆动态键、酰腙和亚胺键。酰基腙键的存在表征了水凝胶的 pH 响应特性。在这项研究中，甘精胰岛素成功地掺入水凝胶中，使其从水凝胶中持续和 pH 响应释放长达 14 天。水凝胶表现出良好的相容性和孔隙结构，水凝胶释放的胰岛素保持其原有的生物活性。在糖尿病大鼠的足部建立全层伤口以评估敷料的治疗效果。结果表明，生物活性胰岛素水凝胶敷料缩短了炎症期，增强肉芽组织形成，促进胶原沉积，加速上皮再形成和新生血管形成，延缓甚至改善周围神经病变，从而显着加速DFUs愈合。我们的研究结果表明，负载胰岛素的水凝胶具有作为多功能生物活性伤口敷料的潜力，可增强 DFU 的愈合。促进胶原沉积，加速上皮再形成和新生血管形成，延缓甚至改善周围神经病变，从而显着加速 DFUs 愈合。我们的研究结果表明，负载胰岛素的水凝胶具有作为多功能生物活性伤口敷料的潜力，可增强 DFU 的愈合。促进胶原沉积，加速上皮再形成和新生血管形成，延缓甚至改善周围神经病变，从而显着加速 DFUs 愈合。我们的研究结果表明，负载胰岛素的水凝胶具有作为多功能生物活性伤口敷料的潜力，可增强 DFU 的愈合。