Plant-derived extracellular nanovesicles in musculoskeletal repair and functional rehabilitation: mitochondrial–immune–metabolic regulation
- 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
- 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Abstract
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.
Related
- Standardized Microplate‐Based Assays for Quantifying Antioxidant Activity in Extracellular Vesicles and Nanovesicles Across Biological Kingdoms
- Platelet-related extracellular vesicles: Therapeutic roles in musculoskeletal disorders.
- Senescent Cell‐Derived Extracellular Vesicles in Therapy‐Induced Senescence: Immune Remodelling and Emerging Links to Mitochondrial Stress in Cancer
- Retinal organoid–based evaluation of icariin-loaded extracellular vesicles for hypoxia-induced retinal injury via mitochondrial modulation
- Extracellular Mitochondrial Components as Emerging Biomarkers and Therapeutic Targets in Human Diseases.
BibTeX
@article{zhu2026plantderived,
title = {{Plant-derived extracellular nanovesicles in musculoskeletal repair and functional rehabilitation: mitochondrial–immune–metabolic regulation}},
author = {Ningning Zhu and Ningrui Wang and NaNa Zhou and Baodong Ye and Jingjing Liu},
journal = {Frontiers in Chemistry},
year = {2026},
month = oct,
doi = {10.3389/fchem.2026.1968520},
url = {https://doi.org/10.3389/fchem.2026.1968520},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Plant-derived extracellular nanovesicles in musculoskeletal repair and functional rehabilitation: mitochondrial–immune–metabolic regulation
AU - Ningning Zhu
AU - Ningrui Wang
AU - NaNa Zhou
AU - Baodong Ye
AU - Jingjing Liu
PY - 2026
DA - 2026/10/12
JO - Frontiers in Chemistry
DO - 10.3389/fchem.2026.1968520
UR - https://doi.org/10.3389/fchem.2026.1968520
AB - 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.
SN - 2296-2646
ER -