Multifunctional polysaccharide-based microneedle system with enzyme cascade reactivity for diabetic wound repair

The disordered healing of diabetic wounds caused by persistent inflammation and disturbed glucose metabolism poses a significant challenge to human health. To address this issue, we develop a multifunctional polysaccharide-based microneedles (MNs) system integrating glucose regulation, tissue adhesion, antibacterial activity, antioxidant activity and biosafety. Dopamine-modified hyaluronic acid (HD) and hydroxypropyltrimethyl ammonium chloride chitosan (HC) are mixed in optimized ratios to utilize their inherent antibacterial and reactive oxygen species (ROS) scavenging functions. Porous silk fibroin microspheres (PSFM), fabricated through a green and porogen-free method by precisely regulating the phase separation kinetics in the dextran/silk fibroin binary system, serve as co-carriers of glucose oxidase (GOD) and catalase (CAT) for enzyme cascade reactions. The HD/HC polysaccharide complex and PSFM co-loaded with GOD and CAT (PSFM@G/C) are integrated into MNs form for effective wound penetration and therapeutic agent delivery. The polysaccharide matrix adheres to tissue for rapid wound closure and performs antibacterial and ROS scavenging functions, while PSFM@G/C efficiently reduce wound glucose levels through the enzyme cascade reaction. The catalytic efficiency of GOD is significantly enhanced through the continuous decomposition of H₂O₂ by CAT during glucose oxidation. The proposed multifunctional MNs system presents a novel and promising strategy for accelerating diabetic wound healing.