A diabetic foot ulcer (DFUs) is a state of prolonged chronic inflammation, which can result in amputation. Different from normal skin wounds, various commercially available dressings have not sufficiently improved the healing of DFUs. In this study, a novel self-healing hydrogel was prepared by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan) and adipic acid dihydrazide (ADH) with hyaluronic acid-aldehyde (HA-ALD), to provide a moist and inflammatory relief environment to promote stem cell proliferation or secretion of growth factors, thus accelerating wound healing. The results demonstrated that this injectable and self-healing hydrogel has excellent swelling properties, stability, and mechanical properties. This biocompatible hydrogel stimulated secretion of growth factors from bone marrow mesenchymal stem cells (BM-MSCs) and regulated the inflammatory environment by inhibiting the expression of M1 macrophages and promoting the expression of M2 macrophages, resulting in granulation tissue formation, collagen deposition, nucleated cell proliferation, neovascularization, and enhanced diabetic wound healing. This study showed that N-chitosan/HA-ALD hydrogel could be used as a multifunctional injectable wound dressing to regulate chronic inflammation and provide an optimal environment for BM-MSCs to promote diabetic wound healing.

糖尿病足溃疡（DFU）是一种长期慢性炎症状态，可能导致截肢。与正常皮肤伤口不同，各种市售敷料并不能充分改善 DFU 的愈合。本研究通过N-羧乙基壳聚糖（ N -chitosan）和己二酸二酰肼（ADH）与透明质酸醛（HA-ALD）原位交联制备了一种新型自修复水凝胶，为透明质酸醛（HA-ALD）提供保湿和抗炎作用。舒缓环境促进干细胞增殖或生长因子分泌，从而加速伤口愈合。结果表明，这种可注射且自修复的水凝胶具有优异的溶胀性能、稳定性和机械性能。这种生物相容性水凝胶刺激骨髓间充质干细胞（BM-MSC）分泌生长因子，并通过抑制M1巨噬细胞的表达和促进M2巨噬细胞的表达来调节炎症环境，从而导致肉芽组织形成、胶原沉积、有核细胞增殖、新血管形成和增强糖尿病伤口愈合。本研究表明， N-壳聚糖/HA-ALD水凝胶可作为多功能可注射伤口敷料来调节慢性炎症，并为BM-MSCs提供最佳环境，促进糖尿病伤口愈合。