Controlled Glutathione‐Releasing Multifunctional Gelatin Methacryloyl/Chitosan/Zeolite Hydrogels for Accelerated Regeneration in Diabetic Wounds

Chronic diabetic wounds remain a major clinical challenge because of persistent inflammation, excessive oxidative stress, impaired angiogenesis, and high susceptibility to infection. This study aims to develop a multifunctional hydrogel system composed of gelatin methacryloyl (GelMA; 7.5%, 10%, 15%), chitosan (2%), zeolite (1%), and glutathione (0.15 mg/mL) that can concurrently deliver antioxidant therapy, prevent infection, and support tissue regeneration in diabetic wounds. All GelMA/chitosan/zeolite/glutathione (Gel-CZG) hydrogels exhibited solid-like viscoelastic behavior and shear-thinning properties, with increasing GelMA concentration yielding higher stiffness. FTIR analysis confirmed the successful incorporation of glutathione, chitosan, and zeolite. SEM imaging revealed a highly interconnected porous microstructure, with pore size decreasing as GelMA concentration increased. Sustained glutathione release was achieved for up to 21 days, following a diffusion-controlled mechanism. The hydrogels were cytocompatible, supported fibroblast adhesion and proliferation, and modulated key inflammatory (e.g., IL-1β, TNF-α, IL-6, MMP13) and regenerative (e.g., IGF1, COL1A1) genes in a concentration-dependent manner. All formulations demonstrated > 90% antibacterial activity against E. coli, S. aureus, and P. aeruginosa and inhibited P. aeruginosa biofilm formation by ≥ 95%. Overall, the designed Gel-CZG hydrogels provide a robust and tunable platform that integrates sustained glutathione delivery, antibacterial action, and regenerative support.