Heterojunction Nanozyme\nHydrogels Containing Cu–O–Zn\nBonds with Strong Charge Transfer for Accelerated Diabetic Wound Healing

The complex microenvironment of persistent inflammation\nand bacterial\ninfection is a major challenge in chronic diabetic wounds. The development\nof nanozymes capable of efficiently scavenging reactive oxygen species\n(ROS) is a promising method to promote diabetic wound healing. However,\nmany nanozymes show rather limited antioxidant activity and ROS-dependent\nantibacterial effects under certain circumstances, further weakening\ntheir ability to scavenge ROS. To meet these challenges, electronically\nregulated bioheterojunction (E-bio-HJ) nanozyme hydrogels derived\nfrom metal–organic frameworks (MOFs) were designed and prepared\nvia an interface engineering strategy. Owing to the electron transfer\nand redistribution effects of the abundant and highly dispersed Cu–O–Zn\nsites at the heterogeneous interface, the E-bio-HJ nanozymes exhibited\ncatalase (CAT)-like activity with ultrahigh hydrogen peroxide affinity\n(<i>K<sub>m</sub></i> = 25.76 mM) and sustained ROS consumption.\nIn addition, owing to the enhanced interfacial effect of E-bio-HJ\nand the good biocompatibility and cell adhesion of the methacryloylated\ngelatin (Gel) hydrogel, the E-bio-HJ gelatin hydrogel (E-bio-HJ/Gel)\nfurther reduced inflammation by inducing macrophage transformation\nto the M2 phenotype, accompanied by excellent antimicrobial properties\nand enhanced cell migration, angiogenesis, and collagen deposition,\nwhich synergistically promoted diabetic wound healing. This highly\neffective and comprehensive strategy offers a new approach for the\nrapid healing of diabetic wounds.