Employing pH/reactive oxygen species (ROS) dual-responsive chitosan/oxidized dextran composite hydrogels based on dual-dynamic bonding to enhance regeneration and repair in diabetic wounds.

Abstract

Diabetic wounds pose considerable therapeutic challenges owing to impaired tissue regeneration and elevated risk of bacterial infection. This study developed a hydrogel-based microenvironment-responsive multifunctional composite system. This composite material comprises a pH/reactive oxygen species (ROS) dual-responsive hydrogel scaffold formed by dihydrocaffeic acid-grafted chitosan and phenylboronic acid-functionalized oxidized dextran hinges, encapsulating gallium ions and ROS-responsive curcumin micelles. Taking advantage of the acidic microenvironment (pH 4.5-6.5) and elevated ROS levels in diabetic wounds, the composites exhibit significant efficacy in inhibiting bacterial biofilm formation, scavenging excess ROS, alleviating inflammatory responses, significantly promoting angiogenesis and collagen deposition. This integrated strategy successfully addresses major challenges in diabetic wound treatment-namely, susceptibility to infection, persistent inflammation, elevated oxidative stress, and impaired angiogenesis by enabling synergistic regulation of antibacterial, anti-inflammatory, antioxidant, and pro-regenerative effects. This comprehensive strategy bridges antimicrobial defense and immune regulation in the context of comprehensive wound management, thereby providing a valuable reference for the development of effective clinical therapies for diabetic wounds.