The healing of chronic diabetic wounds remains a key challenge due to its susceptibility to bacterial infection, the inflammatory wound microenvironment, and difficulty in angiogenesis. Herein, a pH-responsive, mussel-inspired, double-crosslinking injectable, and adhesive smart hydrogel formula was exploited to overcome these obstacles simultaneously. The multifunctional double-crosslinking hydrogel was developed through the formation of catechol−catechol adducts and a Schiff-based reaction between amino groups (−NH₂) in chitosan quaternary ammonium salt (HTCC) and aldehyde groups (-CHO) in oxidized dextran-dopamine (OD-DA). The double-crosslinking mechanism gave the hydrogels great mechanical properties. Most importantly, via the effective encapsulation of silver nanoparticles (AgNPs) and pro-angiogenic drug deferoxamine (DFO), the hydrogel was given with antibacterial and angiogenic features respectively. At the infected diabetic wound area, the double Schiff base bonds (DA and OD; HTCC and OD-DA) in the hydrogels could quickly achieve pH-response and accomplish a sustained and controlled release of drugs to accelerate wound healing. Through the combination of AgNPs and HTCC, the hydrogel exhibited antimicrobial capacities to gram-positive bacteria (S.aureus) and gram-negative bacteria (E.coli), it did not cause toxic side effects and avoided drug resistance. The DFO released at the infected diabetic wound area promoted angiogenesis by enhancing the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). We elucidated the mechanisms by which the designed hydrogels accelerated the healing of bacterial infected diabetic wounds in vitro and in vivo, and our hydrogels represented a general strategy for the healing of a wide range of tissue injuries.

慢性糖尿病伤口的愈合由于其易受细菌感染，炎性伤口微环境和血管生成困难而仍然是关键的挑战。在本文中，开发了一种pH响应，贻贝启发，双交联可注射，粘性智能水凝胶配方，可同时克服这些障碍。通过形成邻苯二酚-邻苯二酚加合物和氨基之间（-NH ₂）在壳聚糖季铵盐（HTCC）和氧化葡聚糖-多巴胺（OD-DA）中的醛基（-CHO）中。双交联机理赋予水凝胶很大的机械性能。最重要的是，通过有效封装银纳米颗粒（AgNPs）和促血管生成药物去铁胺（DFO），水凝胶分别具有抗菌和血管生成特性。在受感染的糖尿病伤口区域，水凝胶中的双席夫碱键（DA和OD； HTCC和OD-DA）可以快速实现pH响应并实现药物的持续和受控释放，从而加速伤口愈合。通过AgNPs和HTCC的结合，水凝胶对革兰氏阳性菌（金黄色葡萄球菌）和革兰氏阴性菌（大肠杆菌）显示出抗菌能力。），它没有引起毒副作用，避免了耐药性。在受感染的糖尿病伤口处释放的DFO通过增强缺氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）的表达来促进血管生成。我们阐明了设计的水凝胶在体外和体内加速细菌感染的糖尿病伤口愈合的机制，我们的水凝胶代表了广泛组织损伤愈合的一般策略。