Journal of Zhejiang University

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Plant-derived exosome-like nanovesicles for orthopaedic diseases: mecha-nisms, delivery strategies, and translational perspectives

Author(s): Zicheng DENG¹, Kailun WU², Ju-Sheng SHIEH³, Moli HUANG^4, 5, Hong LIN^6, 7, Jiong Jiong GUO^1, 4, 8
Affiliation(s): 1Department of Orthopedics and Sports Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China 2Department of Orthopedics, The Fourth Affiliated Hospital of Soochow University/Suzhou Dushu Lake Hospital, Suzhou In-dustrial Park, Suzhou 215125, China 3Department of Periodontology, School of Dentistry, Tri-Service General Hospital and Defense Medical Center, Taipei 11490, China 4MOE Key Laboratory of Geriatric Diseases and Immunology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou 215123, China 5Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, School of Basic Medical Scienc-es, Soochow University, Suzhou 215123, China 6Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China 7Department of Orthopedics, Shanghai Geriatric Medical Center, Fudan University, Shanghai 201104, China 8MOE China-Europe Sports Medicine Belt and Road Joint Laboratory, Soochow University, Suzhou 215006, China
Corresponding email(s): drjjguo@163.com, guojiongjiong@suda.edu.cn
Key Words: Plant-derived exosome-like nanovesicles, Osteoporosis, Osteoarthritis, Bone defects, Drug delivery, Translational medicine

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Zicheng DENG¹, Kailun WU², Ju-Sheng SHIEH³, Moli HUANG^4,5, Hong LIN^6,7, Jiong Jiong GUO^1,4,8,. Plant-derived exosome-like nanovesicles for orthopaedic diseases: mecha-nisms, delivery strategies, and translational perspectives[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2600208

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Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Orthopaedic diseases, including osteoporosis, osteoarthritis, and bone defects, are characterised by dysreg-ulated tissue microenvironments driven by inflammation, oxidative stress, vascular dysfunction, and im-paired cell communication. Strategies targeting single pathways often provide limited durable benefit, highlighting the need for coordinated microenvironmental modulation. Plant-derived exosome-like nano-vesicles (PENs) have emerged as operationally defined bioactive nanovesicles with relevance to orthopae-dic research. While PENs share structural features with mammalian extracellular vesicles, including na-noscale size and lipid bilayer membranes, they are not biogenetically equivalent to mammalian exosomes. Their diverse cargos, low immunogenicity, abundant availability, and intrinsic biological activity may en-able the modulation of osteogenic differentiation, osteoclast activity, inflammatory responses, and angio-genesis. This review synthesises current knowledge on PEN biology, disease-specific therapeutic roles, de-livery strategies, and translational barriers in osteoporosis, osteoarthritis, and bone defect repair. We em-phasise that PEN function and feasibility vary across indications: systemic osteoporosis faces challenges with chronic dosing and standardisation, whereas local applications in osteoarthritis and bone defect repair may offer more tractable translational routes. Engineering approaches, including hydrogels and scaffolds, are key to improving localisation, retention, and controlled presentation. Overall, PENs are best under-stood as complementary bioactive nanovesicles for modulating the orthopaedic microenvironment rather than as direct plant analogues of mammalian exosomes.

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On-line Access: 2026-09-17

Received: 2026-03-31

Revision Accepted: 2026-05-24

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Citations: Bibtex RefMan EndNote GB/T7714

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