pH-Responsive Injectable Multifunctional Pluronic F127/Gelatin-Based Hydrogels with Hydrogen Production for Treating Diabetic Wounds
Tian Zhang, Xin Cheng, Jingya Xiu, Min Liu, Siyi Liu, Bowen Zhang, Qi Miao, Dongyun Cun, Chunrong Yang, Kexin Li, Jiulong Zhang, Xiuli Zhao
Abstract
Diabetic chronic wounds remain a major clinical challenge with long-term inflammatory responses and extreme oxidative damage. Hence, a pH-responsive injectable multifunctional hydrogel [Gel/CUR-FCHO/Mg (GCM) micromotors] via a Schiff base reaction between gelatin and benzaldehyde-grafted Pluronic F127 drug-loaded micelles (FCHO) was fabricated for the first time. Dynamic Schiff base linkage endowed the GCM hydrogel with the ability to be self-healing, injectable, and pH-responsive for on-demand drug delivery at the wound site. Curcumin (CUR), a hydrophobic drug with antioxidative, anti-inflammatory, and antibacterial activities, was encapsulated into the hydrogel matrix by micellization (CUR-FCHO micelles). Simultaneously, magnesium-based micromotors (Mg micromotors) were physically entrapped into the system for providing active hydrogen (H 2 ) to scavenge reactive oxygen species and alleviate inflammatory responses. As a result, the GCM micromotor hydrogel displayed an inherent antibacterial property, extraordinary antioxidative performance, and remarkable biocompatibility. In the diabetic mouse with a full-thickness cutaneous defect wound, the GCM hydrogel could remodel the inflammatory microenvironment and stimulate vascularization and collagen deposition, thereby facilitating wound closure and enhancing tissue regeneration, which offered a promising therapeutic option for diabetic chronic wound management.