An injectable thermosensitive HTCC/Pluronic F127 hydrogel with sustained EGF release for accelerated diabetic wound healing.

Chronic diabetic wounds remain a major clinical challenge owing to persistent bacterial infection, prolonged inflammation, excessive exudation, and impaired tissue regeneration. Herein, an injectable thermosensitive hydrogel was developed by integrating N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan chloride with aldehyde-functionalized Pluronic F127 for epidermal growth factor (EGF) delivery and diabetic wound repair. The hydrogel forms a dual-crosslinked network through temperature-induced micellization and dynamic Schiff base bonding, exhibiting rapid gelation under physiological conditions, shear-thinning behavior, and self-healing properties. In vitro, the hydrogel provides a sustained release profile of EGF exhibiting effective antibacterial activity against Gram-positive S. aureus. In vivo studies in streptozotocin-induced diabetic rats demonstrate significantly accelerated wound healing, achieving 83% wound closure within 14 days compared to 45% in the control group, along with enhanced tissue regeneration characteristics, including improved collagen deposition. This multifunctional hydrogel provides a promising strategy for diabetic wound management by integrating antibacterial potential and tissue regeneration.