ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1615650
This article is part of the Research TopicApplication of Tissue Engineering in Bone, Joints, Ligaments Injuries and Cartilage RegenerationView all 8 articles
Restoration of Tendon Repair Microenvironment by Grapefruit Exosome-Loaded Microneedle System for Tendinopathy Therapy
Provisionally accepted
- 1Department of Orthopedics, First Hospital, Peking University, Beijing, China
- 2Key Laboratory for Regenerative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Region, China
- 3Beijing Key Laboratory of Orthopedic Regenerative Medicine, Chinese PLA General Hospital, Beijing, China
- 4Department of Ophthalmology, Peking University Third Hospital, Beijing, China
- 5Beijing Jishuitan Hospital, Beijing, Beijing Municipality, China
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Tendinitis repair remains challenging due to the limited self-renewal capacity of tenocytes and persistent inflammatory microenvironment. Conventional therapies remain limited by systemic drug toxicity and fail to coordinate immunomodulation with matrix remodeling. Plant-derived extracellular vesicles have demonstrated tissue repair potential owing to their unique bioactive components and exceptional cross-species compatibility. Nevertheless, their therapeutic role in tendon matrix regeneration remains underexplored. Here, we developed a grapefruit-derived exosome-loaded microneedle patch (MN@GF-Exos) to synergistically restored tendon structure and functions.Grapefruit-derived exosomes (GF-Exos) were loaded into dissolvable hyaluronic acid microneedles (MNs) for sustained release. GF-Exos reversed oxidative stress in tenocytes, enhancing cellular proliferation and migration, restoring collagen I synthesis, and polarizing macrophages toward M2repair phenotypes. Transcriptomics revealed GF-Exos modulated cytokine-cytokine receptor interactions, suppressing inflammation-related pathways and activating ECM organization genes. In collagenase-induced tendinopathy mice, MN@GF-Exos enhanced gait recovery and extracellular matrix remodeling. Histology confirmed reduced fibrosis without ectopic ossification. Systemic safety was validated by unchanged organ histology and within-normal-limits serum biomarkers. This dualfunctional system leverages plant exosomes' multi-component synergy and MN's spatiotemporal control, offering a translatable strategy for chronic tendon regeneration.
Keywords: Tendinopathy, grapefruit-derived exosome, microneedles, Oxidative Stress, Macrophage polarization
Received: 21 Apr 2025; Accepted: 15 Jul 2025.
Copyright: © 2025 Zhang, Zhang, Zhang, Mu, Juma, Li, Li, Guo and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hao Li, Beijing Key Laboratory of Orthopedic Regenerative Medicine, Chinese PLA General Hospital, Beijing, China
Quanyi Guo, Beijing Key Laboratory of Orthopedic Regenerative Medicine, Chinese PLA General Hospital, Beijing, China
Yongping Cao, Department of Orthopedics, First Hospital, Peking University, Beijing, China
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