DOI: 10.32098/mltj_2026_6611

Efficacy and safety of exosomes and extracellular vesicles in the management of rotator cuff injury: A systematic review of in vivo studies

Authors

  • Widya Khairunnisa Sarkowi Faculty of Medicine, IPB University, Bogor City, Indonesia
  • Stephen Ivano Chiuvan Faculty of Medicine, IPB University, Bogor City, Indonesia
  • Rifqi Kamil Amaanullah Faculty of Medicine, IPB University, Bogor City, Indonesia
  • Dafrina Kalyla Lofriman Faculty of Medicine, IPB University, Bogor City, Indonesia
  • Khalilah Ghina Salsabila Faculty of Medicine, IPB University, Bogor City, Indonesia
  • Pradiptha Aryasena Faculty of Medicine, IPB University, Bogor City, Indonesia
  • Auliya Akbar Faculty of Medicine, IPB University, Bogor City, Indonesia

auliyaakbarmd.ortho@gmail.com

Keywords

Exosomes, extracellular vesicles, rotator cuff injuries, tendon repair, in vivo

Abstract

Introduction: Rotator cuff tendon is vulnerable to acute and chronic injuries, leading to pain, reduced mobility, and decreased quality of life. Recovery is slow and frequently results in fibrotic changes, impairing full functional restoration. Currently, exosomes and extracellular-vesicles (EVs) have emerged as promising regenerative approaches for tendon. However, no clinical studies in humans have been reported for its use in rotator cuff injury. Therefore, this review aims to evaluate the efficacy and safety of exosomes/EVs in animal models of rotator cuff injury, as a foundation for clinical translation.

Methods: A systematic search was conducted following PRISMA guidelines across PubMed, Scopus, Wiley, and EBSCOhost. Eligible studies included animal models of rotator cuff injury treated with exosomes/EVs. Data on exosomes/EVs characteristics, animal model, outcomes, and follow-up duration were extracted. Risk of bias was assessed using SYRCLE RoB tool.

Results: Eleven studies were included in the review, involving 63 mice, 210 rats, 211 rabbits, and 12 sheep. Variations were noted in sources, concentration, and delivery methods for exosomes/EVs across studies. Exosomes/EVs demonstrated superior outcomes in tendon repair compared to controls, with improvements observed in macroscopic, histological, and biomechanical outcomes. Proposed mechanisms included enhanced extracellular matrix remodeling, reduced fatty infiltration, anti-inflammatory, and immune-modulation. Quality of included studies was generally moderate, with some studies exhibiting some risk of bias.

Conclusion: Exosome and EVs might be effective for rotator cuff injury in animal models with minimum side effects. Further preclinical studies and clinical trials are necessary to validate efficacy and safety in humans.

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Published

2026-03-31

How to Cite

1.
Sarkowi WK, Chiuvan SI, Amaanullah RK, Lofriman DK, Ghina Salsabila K, Aryasena P, et al. Efficacy and safety of exosomes and extracellular vesicles in the management of rotator cuff injury: A systematic review of in vivo studies. MLTJ [Internet]. 2026 Mar. 31 [cited 2026 Nov. 12];16(1). Available from: https://mltj.online/index.php/mltj/article/view/6611