Skin regeneration axis under metal-based nanozymes: from chronic wound healing to structural and functional...

Diabetic infected wounds, representing a prototypical model of chronic non-healing wounds, leading to severe impairment of skin regeneration. However, complete skin restoration requires more than just wound closure; it crucially involves the inhibition of pathological scarring (fibrosis) and the functional regeneration of skin appendages (e.g., hair follicles). Metal-based nanozymes (MNZs), due to their highly stable, tunable enzyme-mimicking catalytic activity and excellent integration potential, have emerged as promising candidates, with initial studies demonstrating their utility in these broader regenerative aspects. But existing reviews primarily focus on MNZs' role in basic wound healing, overlooking the structure and functional regeneration potential of skin under MNZs intervention.

This review addresses the knowledge gap by analyzing the recent literature to establish a comprehensive "Skin Regeneration Axis" for MNZs application. Specifically, the objective is to integrate and evaluate MNZs' potential across the three essential dimensions of full-process skin repair: chronic wound healing, structural pathological scar inhibition, and functional appendage regeneration. This integration fully reports MNZs' potential for holistic skin restoration.

This review summarizes the fundamentals of MNZs, including their catalytic mechanisms, classifications, and synthetic strategies. It articulates a multidimensional regenerative paradigm for MNZs, elucidating their roles across the entire spectrum of skin regeneration, which constitutes the core concepts of this review: (1) Chronic Wound Healing via controlling inflammation and oxidative stress, (2) Pathological Scar Inhibition through targeted molecular pathway regulation, and (3) Structural Appendage Regeneration (e.g., hair follicles). The review also highlights critical translational challenges and proposes integrated strategies for accelerating the clinical application of MNZs for holistic skin repair.