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.
Jul 2026· Journal of materials chemistry. B· Vol 14, pp. 10101-10112· 0 citations
Medicine
TL;DR
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.
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.
A multifunctional, mechanism-targeted strategy that provides a rational, disease-relevant approach for treating chronic diabetic wounds by dampening inflammatory signaling and protecting reparative cells is developed.
Yuefei Zhu, Na Yan, Yongqiang Xiao et al.· Small· 0 citations
Through synergistic ROS scavenging and the release of active Zn and Ce ions, this system restored endothelial cell proliferation, migration, and tubulogenic capacity, which are typically impaired under high-glucose conditions, ultimately promoting rapid diabetic wound healing.
Songjie Li, Han Chen, Xin Dan et al.· Nano Reseach· 0 citations
Infected wounds with bacterial biofilms remain a clinical challenge due to persistent inflammation, excessive reactive oxygen species (ROS), and insufficient therapeutic functions of conventional dressings. Current pH-responsive hydrogels suffer from mismatched degradation and limited microenvironment regulation, while free nanozymes or recombinant collagen alone cannot address the complex wound healing cascade. Herein, a bacterial infection microenvironment-responsive hydrogel (CuTA/rHCIII@Hydrogel) was developed by incorporating copper-tannic acid coordination (CuTA) nanozyme and recombinant human type III collagen (rHCIII) into an oxidized dextran/gelatin matrix formed via dynamic Schiff base bonds. The hydrogel exhibited injectability, self-healing, and acidic pH-responsive degradation. In the acidic infected wound microenvironment, the hydrogel could responsively degrade by simultaneously release CuTA and rHCIII. CuTA nanozyme exerted excellent antibacterial effects through disrupting bacterial membranes, inducing intracellular copper ion stress, and causing DNA damage. Meanwhile, CuTA possessed superoxide dismutase- and catalase-mimicking activities to efficiently scavenge ROS, thereby alleviating oxidative stress and promoting M2-type macrophage polarization. The released rHCIII synergistically enhanced cell migration and upregulates CD31 and vascular endothelial growth factor (VEGF) to promote angiogenesis. Leveraging its combined antibacterial, anti-inflammatory, microenvironment-remodeling, and pro-regenerative capabilities, the CuTA/rHCIII@Hydrogel markedly accelerated the repair of infected wounds, establishing it as a promising platform for treating refractory infected wounds.
Mingyang He, Hui Li, Yan Yang et al.· International Journal of Bio...· 0 citations
In vivo, AP@EM-gel produced near-complete wound closure by day 14 and improved bacterial clearance, re-epithelialisation, collagen organisation, angiogenesis, and inflammatory resolution compared with the commercial dressing.
Rui Zhang, Suk Fei Tan, Ye Wang et al.· Frontiers in Cell and Develo...· 0 citations
A precision-engineered hydrogel that integrates structural integrity with environment-triggered delivery and seamlessly coupling nanocontrolled release with microenvironmental sensing is presented, presenting a precision-engineered platform for the synergistic treatment of recalcitrant diabetic wounds.
