Multifunctional nanozyme-embedded hydrogels for advanced diabetic wound management

Abstract

Diabetes mellitus imposes a substantial global healthcare burden due to its chronic progression and associated complications. Diabetic wound healing is severely compromised by hyperglycemia-induced pathological alterations, including osmotic imbalance, bacterial proliferation, and impaired tissue regeneration. Critically, excessive reactive oxygen species (ROS) in the wound microenvironment perpetuate inflammation, degrade extracellular matrix (ECM), and delay healing, necessitating advanced therapeutic dressings. Hydrogels emerge as ideal candidates owing to their high hydration capacity, biocompatibility, and structural mimicry of native ECM. Nanozymes (NZs)—nanomaterials with enzyme-mimetic catalytic activities (e.g., superoxide dismutase, catalase)—offer superior stability and catalytic efficiency compared to natural enzymes. Integrating NZs into hydrogels yields multifunctional nanozyme-embedded hydrogels (NZ@hydrogels) that synergistically combine ROS scavenging, antimicrobial action, and pro-healing functions. This review systematically analyzes diverse NZ@hydrogel systems leveraging enzymatic mechanisms (e.g., glucose oxidase-like, peroxidase-like activities) for diabetic wound therapy, emphasizing their roles in modulating inflammatory responses, hypoxia alleviation, and angiogenesis promotion. Current translational challenges, including biocompatibility optimization, long-term biosafety assessment, and scalable manufacturing, are critically evaluated. Future perspectives focus on accelerating clinical adoption through advanced material design and rigorous preclinical validation, aiming to stimulate transformative research in precision wound management.