Prolonged, intense inflammation and excessive oxidative stress hinder diabetic wounds from healing normally, leading to disorders downstream including the postponement of re-epithelialization and extracellular matrix (ECM) formation. Herein, we report a hyaluronic acid (HA) and chitosan based hydrogel (OHA-CMC) with inherent antibacterial and hemostatic activities fabricated via Schiff base reaction. By encapsulating nanotechnologically-modified curcumin (CNP) and epidermal growth factor (EGF) into the hydrogel, OHA-CMC/CNP/EGF exhibited extraordinary antioxidant, anti-inflammatory, and migration-promoting effects in vitro. Meanwhile, OHA-CMC/CNP/EGF presented on-demand drug release in synchrony with the phases of the wound healing process. Specifically, curcumin was rapidly and constantly released to alleviate inflammation and oxidative stress in the early phase of wound healing, while a more gradual and sustained release of EGF supported late proliferation and ECM remodeling. In a diabetic full-thickness skin defect model, OHA-CMC/CNP/EGF dramatically improved wound healing with ideal re-epithelialization, granulation tissue formation, and skin appendage regeneration, highlighting the enormous therapeutic potential this biomaterial holds as a diabetic wound dressing.

长时间、强烈的炎症和过度的氧化应激会阻碍糖尿病伤口的正常愈合，导致下游疾病，包括上皮再形成和细胞外基质 (ECM) 形成的延迟。在此，我们报告了一种透明质酸 (HA) 和壳聚糖基水凝胶 (OHA-CMC)，通过席夫碱反应制造，具有固有的抗菌和止血活性。通过将纳米技术修饰的姜黄素 (CNP) 和表皮生长因子 (EGF) 封装到水凝胶中，OHA-CMC/CNP/EGF 在体外表现出非凡的抗氧化、抗炎和促进迁移的作用。同时，OHA-CMC/CNP/EGF 呈现与伤口愈合过程阶段同步的按需药物释放。具体来说，姜黄素在伤口愈合的早期迅速且持续地释放以减轻炎症和氧化应激，而 EGF 的更渐进和持续的释放支持晚期增殖和 ECM 重塑。在糖尿病全层皮肤缺损模型中，OHA-CMC/CNP/EGF 通过理想的上皮再形成、肉芽组织形成和皮肤附件再生显着改善了伤口愈合，突出了这种生物材料作为糖尿病伤口敷料的巨大治疗潜力。