Nanozyme-based biomaterials: Orchestrating microenvironmental homeostasis for advanced musculoskeletal tissue regeneration

The repair and regeneration of musculoskeletal tissues pose significant challenges in clinical practice. These issues are often compounded by factors such as aging, trauma, infection, or metabolic diseases, and are accompanied by pathological microenvironments characterized by oxidative stress, immune imbalance, and vascular damage. Nanozymes—functional nanomaterials endowed with enzyme-like catalytic activity—represent a promising therapeutic paradigm for bone-related diseases, owing to their outstanding structural stability, tunable and versatile catalytic performance, and capacity for multifunctional integration. This review systematically outlines the pathological features and unmet clinical needs associated with bone defects and musculoskeletal diseases. It subsequently offers a systematic and in-depth overview of nanozymes, encompassing their fundamental definition, structural classification, diverse catalytic activities, and underlying catalytic mechanisms. Based on this, the review highlights the representative applications of nanozymes in the repair of complex bone defects, bone infections, muscle-tendon injuries, lumbar disc degeneration, and spinal cord injuries. These applications involve modulation of inflammatory responses, immune system regulation, bone and cartilage microenvironmental control, coupling of vascular/neural bone regeneration, and intervention in key signaling pathways. Finally, the challenges and future trends of nanozymes in the field of musculoskeletal diseases are discussed, providing insights for rational design and clinical translation.