Dual-crosslinked mussel-inspired smart hydrogels with enhanced antibacterial and angiogenic properties for chronic infected diabetic wound treatment via pH-responsive quick cargo release
Dual-crosslinked mussel-inspired smart hydrogels with enhanced antibacterial and angiogenic properties for chronic infected diabetic wound treatment via pH-responsive quick cargo release
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DOI：
10.1016/j.cej.2021.128564
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发表时间：
2021-01-23
影响因子：
15.1
通讯作者：
Wang, Yunbing
中科院分区：
文献类型：
--
作者：
Hu, Cheng;Long, Linyu;Wang, Yunbing
慢性糖尿病伤口的愈合仍然是一个关键的挑战，因为它对细菌感染，炎症性伤口微环境和血管生成的困难。本文中，利用pH响应性、贻贝启发、双交联可注射和粘合剂智能水凝胶配方来同时克服这些障碍。通过壳聚糖季铵盐（HTCC）中的氨基（-NH 2）与氧化葡聚糖-多巴胺（OD-DA）中的醛基（-CHO）发生席夫碱反应，生成邻苯二酚-邻苯二酚加合物，制备了多功能双交联水凝胶。双交联机理赋予了水凝胶优异的力学性能。最重要的是，通过有效包裹银纳米颗粒（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功能。在糖尿病感染创面，水凝胶中的双Schiff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控制释放，以加速伤口愈合。通过AgNPs和HTCC的组合，水凝胶表现出对革兰氏阳性菌（S. aureus）和革兰氏阴性菌（E. coli），无毒副作用，避免了耐药性。在感染的糖尿病伤口区域释放的DFO通过增强缺氧诱导因子-1 α（HIF-1 α）和血管内皮生长因子（VEGF）的表达来促进血管生成。我们阐明了所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，并且我们的水凝胶代表了广泛组织损伤愈合的一般策略。
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 hypoxiainducible factor-1 alpha (HIF-1 alpha) 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.