Combating antimicrobial resistance with ROS-generating biomaterials: Mechanisms, applications, and translational challenges

Antimicrobial resistance (AMR) has escalated into a critical global health crisis as the efficacy of conventional single-target antibiotics continues to diminish against rapidly evolving pathogens, prompting exploration of reactive oxygen species (ROS)-based antibacterial biomaterials that offer a multi-targeted oxidative mechanism to circumvent traditional resistance pathways. This narrative review systematically delineates the primary ROS-generation strategies, including photodynamic therapy, sonodynamic therapy, catalytic nanozymes, metal/metal-oxide systems, and stimuli-responsive polymeric systems. We elucidate how ROS species, encompassing superoxide anions, hydrogen peroxide, hydroxyl radicals, and singlet oxygen, effectively oxidize bacterial proteins, lipids, DNA, and extracellular biofilm matrices, thereby exhibiting potent activity against multidrug-resistant strains. Notably, ROS-mediated oxidative damage can bypass conventional resistance mechanisms, such as enzymatic drug inactivation, target-site modifications, reduced membrane permeability, and active efflux. Key therapeutic applications are prominently identified in chronic wound healing, orthopedic implant-associated infections, and oral biofilm control. Despite considerable promise, four persistent translational barriers are as follows: inherent non-selective cytotoxicity toward mammalian host tissues, poor penetrability through dense biofilm exopolysaccharides matrix, insufficient spatiotemporal control and infection-site specificity, and a notable lack of standardized long-term biosafety assessments. In conclusion, ROS-driven biomaterials represent a transformative yet clinically nascent strategy against AMR. Successful translation will critically depend on future engineering that prioritizes precision targeting and on-demand ROS activation to confine oxidative damage strictly to bacterial microenvironments. Ultimately, ROS constitute a uniquely versatile and evolutionarily conserved antibacterial axis; however, bridging the gap between experimental promise and practical deployment requires rigorous integration of robust antibacterial efficacy with stringent host biocompatibility, site specificity, and validated long-term safety profiles.