Biofilm-disrupting heterojunction microneedles: dual ROS amplification and glucose deprivation for accelerated diabetic wound healing.

Abstract

Rationale: Diabetic wound healing process is critically hindered by bacterial infection, bacterial biofilm formation, and persistent hyperglycemia. Biomolecular microneedles represent a promising alternative to conventional therapies such as antibiotics and antibiotic-loaded wound dressings, owing to the advantages like reduced risk of drug resistance and enhanced long-term efficacy. However, the microneedles that fulfill the clinical needs of diabetic wounds have rarely been reported. Methods: A glucose oxidase (GOx)-laden Ti₃C₂/In₂O₃ (INTG) heterojunction was engineered as a nano-micro platform for reactive oxygen species (ROS) amplification and glucose deprivation, and subsequently immobilized onto the gelatin methacryloyl (GelMA) microneedle tips to obtain double-layer microneedles (GITG microneedles). Their physiochemical properties and biomedical applications were comprehensively investigated. Results: For INTG heterojunction, the formation of Schottky structure significantly improved the oxygen absorption capacity, facilitated the generation and migration of photogenerated electron-hole pairs, thereby promoting the ROS generation. Besides, under near-infrared (NIR) irradiation, GITG microneedles effectively inhibited bacterial proliferation and survival by generating ROS, thereby preventing the formation of bacterial biofilm. Additionally, GITG microneedles accelerated wound closure and facilitated skin tissue regeneration in a rat model through multiple mechanisms. Conclusion: This study developed an advanced microneedle platform enabling on-demand multimodal treatment, demonstrating significant potential for clinical diabetic wound management.