Heterojunction Nanozyme Hydrogels Containing Cu–O–Zn Bonds with Strong Charge Transfer for Accelerated Diabetic Wound Healing

The complex microenvironment of persistent inflammation and bacterial infection is a major challenge in chronic diabetic wounds. The development of nanozymes capable of efficiently scavenging reactive oxygen species (ROS) is a promising method to promote diabetic wound healing. However, many nanozymes show rather limited antioxidant activity and ROS-dependent antibacterial effects under certain circumstances, further weakening their ability to scavenge ROS. To meet these challenges, electronically regulated bioheterojunction (E-bio-HJ) nanozyme hydrogels derived from metal–organic frameworks (MOFs) were designed and prepared via an interface engineering strategy. Owing to the electron transfer and redistribution effects of the abundant and highly dispersed Cu–O–Zn sites at the heterogeneous interface, the E-bio-HJ nanozymes exhibited catalase (CAT)-like activity with ultrahigh hydrogen peroxide affinity (Km = 25.76 mM) and sustained ROS consumption. In addition, owing to the enhanced interfacial effect of E-bio-HJ and the good biocompatibility and cell adhesion of the methacryloylated gelatin (Gel) hydrogel, the E-bio-HJ gelatin hydrogel (E-bio-HJ/Gel) further reduced inflammation by inducing macrophage transformation to the M2 phenotype, accompanied by excellent antimicrobial properties and enhanced cell migration, angiogenesis, and collagen deposition, which synergistically promoted diabetic wound healing. This highly effective and comprehensive strategy offers a new approach for the rapid healing of diabetic wounds.