Micro-environment triple-responsive hyaluronic acid hydrogel dressings to promote antibacterial activity, collagen deposition, and angiogenesis for diabetic wound healing

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-05, Vol.12 (19), p.4613-4628
• Main Authors: Wang, Wenquan, Zheng, Jingxia, Hong, Xiaojing, Zhou, Jiaying, Xiong, Yuwen, Yang, Hailong, Li, Shengnan, Chen, Guoqi, Su, Qiao, Li, Wenwen, Cheng, Bin, Fu, Jun, Wu, Tong
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antibiotics; Bandages; Collagen - chemistry; Controlled release; Cross-linking; Deposition; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Escherichia coli - drug effects; Extracellular matrix; Glucose; Humans; Hyaluronic acid; Hyaluronic Acid - chemistry; Hyaluronic Acid - pharmacology; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Inflammation; Male; Mice; Microbial Sensitivity Tests; Neovascularization, Physiologic - drug effects; Reactive oxygen species; Reactive Oxygen Species - metabolism; Regeneration (biological); Regeneration (physiology); Staphylococcus aureus - drug effects; Sustained release; Tannic acid; Tannins - chemistry; Tannins - pharmacology; Tissue engineering; Wound healing; Wound Healing - drug effects
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d4tb00261j

The clinical treatment of chronic diabetic wounds is a long-standing thorny issue. Strategies targeting the diabetic micro-environment have been developed to promote wound healing. However, it remains challenging to reverse the adverse conditions and re-activate tissue regeneration and angiogenesis. In this work, we develop injectable hydrogels that are responsive to acidic conditions, reactive oxygen species (ROS), and high glucose levels in a diabetic wound micro-environment to sustainably deliver tannic acid (TA) to augment antibacterial, anti-inflammatory, and anti-oxidative activities. This triple-responsive mechanism is designed by introducing dynamic acylhydrazone and phenylboronic ester bonds to crosslink modified hyaluronic acid (HA) chains. At a diabetic wound, the acylhydrazone bonds may be hydrolyzed at low pH. Meanwhile, glucose may compete with TA, and ROS may oxidize the C-B bond to release TA. Thus, sustained release of TA is triggered by the diabetic micro-environment. The released TA effectively scavenges ROS and kills bacteria. In vivo experiments on diabetic mice demonstrate that the hydrogel dressing highly promotes angiogenesis and extracellular matrix (ECM) deposition, leading to eventual full healing of diabetic skin wounds. This micro-environment-triggered triple-responsive drug release provides a promising method for chronic diabetic wound healing. pH/ROS/glucose triple-responsive OAH@TA hydrogel elicits controlled TA release, enhancing antibacterial, anti-inflammatory, and antioxidative properties to facilitate diabetic wound healing.