From ROS scavenging to microenvironment remodeling: nanocatalytic strategies for wound healing and tissue regeneration

Nanocatalytic medicine has emerged as a promising strategy for the treatment of chronic wounds by enabling active modulation of the pathological wound microenvironment. Chronic non-healing wounds are characterised by persistent inflammation, microbial infection, oxidative stress, tissue hypoxia, and impaired vascularisation, which together create a hostile environment that prevents effective tissue regeneration. Although considerable progress has been made in the development of nanocatalysts for reactive oxygen species regulation and antibacterial therapy, many existing systems are primarily evaluated according to individual catalytic or therapeutic functions and do not adequately consider the dynamic interactions among redox status, cellular metabolism, and tissue repair. In this review, we discuss the transition from simple ROS scavenging toward comprehensive microenvironment remodeling through the concept of a catalytic landscape within the wound bed. Particular attention is given to the regulation of endogenous substrates, including H₂O₂, glucose, and O₂, and to the effects of catalytic activity, active-site properties, and cascade reactions on the wound microenvironment. We further examine how nanocatalytic regulation of redox and oxygen homeostasis influences mitochondrial function, macrophage phenotypes, endothelial angiogenic responses, and extracellular matrix remodelling. Recent advances in stimuli-responsive, spatiotemporally controlled, and self-regulating nanocatalytic systems are also summarised, with emphasis on their potential to coordinate antibacterial activity with subsequent tissue regeneration. In addition, we discuss the integration of nanocatalysts with hydrogels and microneedle-based delivery systems to improve spatial localization and therapeutic efficiency. Finally, key challenges associated with protein corona formation, catalytic behavior in vivo, safety evaluation, dose control, and large-scale manufacturing are discussed. This review highlights the importance of developing bio-interactive and dynamically regulated nanocatalytic systems and provides perspectives for their translation into next-generation wound therapeutics.