Frontiers in Chemistry · Oct 12, 2026

Plant-derived extracellular nanovesicles in musculoskeletal repair and functional rehabilitation: mitochondrial-immune-metabolic regulation

By Zhu N, Wang N, Zhou N et al.

Musculoskeletal injuries and degenerative disorders caused by trauma, aging, chronic inflammation, and metabolic dysfunction frequently result in impaired functional recovery, including skeletal muscle atrophy, bone loss, cartilage degeneration, and neuromuscular dysfunction. Although exercise rehabilitation, physical therapy, and pharmacological interventions can improve clinical outcomes, their ability to restore the complex pathological microenvironment characterized by persistent inflammation, oxidative stress, mitochondrial dysfunction, and metabolic imbalance remains limited. Plant-derived extracellular nanovesicles (PELNs), naturally occurring lipid-bilayer nanoparticles containing diverse bioactive cargos such as RNAs, proteins, lipids, and phytochemicals, have recently emerged as promising regulators of tissue repair. Unlike conventional nanoparticles that mainly serve as passive delivery carriers, PELNs possess intrinsic biological activity and can actively modulate cellular states across biological barriers. Increasing evidence indicates that PELNs contribute to musculoskeletal regeneration by regulating inflammatory responses, oxidative stress, mitochondrial homeostasis, stem/progenitor cell activity, and extracellular matrix remodeling. Recent studies have reported regenerative effects of PELNs in experimental models involving skeletal muscle, bone, and peripheral nerve tissues. Beyond tissue-specific effects, accumulating evidence suggests that PELN-mediated regeneration involves coordinated mitochondrial-immune-metabolic reprogramming, including regulation of mitochondrial quality control, inflammatory signaling, and immunometabolic states. This review summarizes recent advances in PELN-mediated musculoskeletal repair and their potential relevance to functional recovery, highlighting their biological properties, therapeutic applications, and underlying regulatory mechanisms. The challenges and future perspectives of engineered PELNs for regenerative rehabilitation are also discussed.

doi.org/10.3389/fchem.2026.1968520Open accessPubMed 42936525Interventions