All-Natural Immunomodulatory Bioadhesive Hydrogel Promotes Angiogenesis and Diabetic Wound Healing by Regulating Macrophage Heterogeneity

The study developed an all-natural hydrogel dressing, FGMA/FG/PA, aimed at enhancing diabetic wound healing by modulating the immune microenvironment and promoting angiogenesis through macrophage heterogeneity regulation. The hydrogel, composed of fish gelatin and protocatechuic aldehyde, demonstrated strong bioadhesive properties, antibacterial effects, and ROS scavenging abilities, facilitating the polarization of macrophages to the anti-inflammatory M2 phenotype. This polarization led to the release of growth factors like TGF-β and VEGF, promoting angiogenesis and improving wound healing. The hydrogel showed superior performance compared to commercial dressings, with optimized mechanical properties for wound movement and closure. It demonstrated significant antibacterial effects, particularly with 2% PA content, and promoted macrophage polarization, enhancing angiogenesis and accelerating wound healing. The hydrogel's bioactivity, biosafety, and cost-effectiveness highlighted its potential for clinical application in diabetic wound treatment and other immune-related diseases.