Click-Chemistry-Based Antibacterial Hybrid Hydrogel with Sustained Puerarin Release for Diabetic Wound Healing.

The abnormal microenvironment of chronic diabetic wounds leads to the disorder of the tissue repair process. Herein, based on the principles of click chemistry, a multifunctional rapid gelation hydrogel dressing (MSFP hydrogel) was designed for the treatment of diabetic wounds. The hydrogel was formed via thiol-ene click reaction between thiolated Pluronic F127 (F127SH) and maleimide-modified gelatin (GelatinMAL). This thiol-ene click reaction required no metal catalyst, exhibited good biocompatibility, and proceeded under mild conditions. The system incorporated antimicrobial component F127-acetylbromide (F127AcBr) and puerarin (PUE) and responded to overexpressed matrix metalloproteinase 9 (MMP-9) at wound sites, enabling controlled drug release. In vitro experiments demonstrated that the MSFP hydrogel effectively eliminated ROS; modulated macrophage polarization; promoted human umbilical vein endothelial cell proliferation, migration, and tube formation; and exhibited robust antibacterial activity against Staphylococcus aureus and Escherichia coli. In vivo diabetic mouse wound models confirmed that the MSFP hydrogel synergistically improved the wound microenvironment by establishing barrier protection, inhibiting bacterial growth, reducing inflammation, promoting M2 macrophage polarization, and enhancing vascularization. Collectively, this multifunctional hydrogel can promote diabetic wound healing through immunoregulation, angiogenesis, and antibacterial activity, presenting a promising therapeutic strategy for clinical application.