Nanotechnology-mediated strategies for skeletal muscle repair and regeneration: targeted intervention, functional remodeling, and translational challenges

Skeletal muscle is an important locomotor and metabolic organ in the human body and plays a central role in maintaining physical activity, energy homeostasis, and structural support. Although skeletal muscle possesses a certain regenerative potential, under pathological conditions such as aging, severe trauma, pathogen infection, myogenic malignancies, and other metabolic diseases, its repair process is often accompanied by impaired myogenic differentiation, inflammatory and oxidative stress imbalance, insufficient vascularization, and limited innervation, ultimately leading to structural muscle damage and functional impairment. These changes not only severely affect patients' quality of life but also impose a substantial economic burden on healthcare systems, making them an urgent public health issue. Existing therapeutic strategies, including pharmacological treatment, physical interventions, and surgical procedures, can alleviate symptoms to some extent. However, they generally remain limited by insufficient targeting, restricted local bioavailability, and unstable long-term efficacy. In recent years, nanotechnology has shown considerable application potential in skeletal muscle regeneration and related disease intervention, owing to its tunable physicochemical properties, delivery advantages, and tissue-biomimetic capabilities. Based on the specific pathological characteristics of skeletal muscle diseases, this Review systematically summarizes recent advances in nanotechnology, including drug delivery, scaffold construction, nanozyme design, and biomimetic tissue engineering. Particular emphasis is placed on their potential roles in promoting myogenic differentiation, alleviating inflammation and oxidative stress, combating infection and myogenic malignancies, supporting vascularization, and facilitating the recovery of neural structure and function. In addition, this Review further analyzes the clinical challenges and future directions of nanotechnology in the field of skeletal muscle diseases, aiming to provide a reference for related research and the optimization of therapeutic strategies for skeletal muscle disorders.