Antioxidant nanozymes for periodontal bone regeneration: multifunctional mechanisms and therapeutic applications

The regeneration of periodontitis-related bone defects remains a significant clinical challenge due to the complex and dynamic pathological microenvironment. The primary barrier stems from a self-perpetuating cycle driven by plaque biofilm-induced chronic inflammation, hypoxia, and the consequent overproduction of reactive oxygen species (ROS). Conventional therapeutic approaches are often inadequate in simultaneously targeting these interconnected pathological factors, leading to suboptimal tissue regeneration. In recent years, as an emerging nanobiomaterial, antioxidant nanozymes have provided a promising solution for overcoming the aforementioned therapeutic bottlenecks, owing to their tunable catalytic activity, high stability, and excellent biocompatibility. This review systematically examines the multifaceted roles of ROS in the pathogenesis of periodontitis, with particular emphasis on their suppressive effects on the osteogenic niche. We provide an in-depth analysis of the catalytic mechanisms and design strategies of various antioxidant nanozymes exhibiting superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-like activities, and highlight their multifunctional applications in periodontal therapy. These include direct antibacterial and anti-biofilm actions, modulation of the immune-inflammatory milieu to promote macrophage M2 polarization, and facilitation of both osteogenesis and angiogenesis. Notably, the field has advanced from early single-function antioxidants toward the development of intelligent, stimuli-responsive nanoplatforms that integrate multiple enzymatic activities and environmental responsiveness, enabling precise sensing and adaptive intervention within the intricate periodontal microenvironment. Finally, we discuss key challenges facing future research and the translational potential of nanozyme-based therapies, aiming to establish a solid theoretical framework and guide the development of next-generation strategies for periodontitis treatment.