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Peer-reviewedCC BY-NC-ND 4.0Journal of Nanobiotechnology

Enhanced exosome biomanufacturing, precision isolation, and advanced engineering: toward mechanistic regulation and biomaterial integration for osteoarthritis therapy

4 affiliations
  1. 1Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
  2. 2Chongqing Medical University, Chongqing Medical University, Chongqing, China
  3. 3Department of Pharmacy, The Cangnan Hospital of Wenzhou Medical University, Wenzhou, 325800 Zhejiang China
  4. 4Department of Orthopaedic Surgery, Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

Abstract

Exosomes (Exos) are nanoscale extracellular vesicles that have gained attention as promising therapeutic agents due to their unique biological attributes, immunomodulatory roles, and potential for targeted drug delivery. This review systematically explores their biological origins, secretion mechanisms, and cellular uptake dynamics of Exos. We explore strategies to enhance Exos production, including genetic modifications and optimized culture conditions, and compare purification methods such as ultracentrifugation and size-exclusion techniques, noting their advantages and disadvantages. Additionally, we discuss the engineering of Exos for drug delivery applications through methods like electroporation and physicochemical modifications. Focusing on osteoarthritis (OA)—a widespread degenerative joint disorder lacking effective clinical treatments for halting its progression or promoting cartilage regeneration—we elaborate on the therapeutic mechanisms of Exos in this context, including regulation of inflammatory responses, enhancement of chondrocyte survival, promotion of matrix synthesis, and inhibition of pathological angiogenesis via bioactive molecules like microRNAs and proteins. To address the challenges of rapid clearance and insufficient targeting in vivo, we propose innovative delivery systems using polymer-based and natural biomaterials to improve Exos retention and stability within the joint cavity. This approach aims to optimize therapeutic outcomes and bridge fundamental biological research with clinical applications, advancing next-generation OA treatment strategies.

Graphical abstract:

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BibTeX
@article{gao2026enhanced,
  title = {{Enhanced exosome biomanufacturing, precision isolation, and advanced engineering: toward mechanistic regulation and biomaterial integration for osteoarthritis therapy}},
  author = {Meipei Gao and Qiaotian Yin and Zejian Zhong and Zhuoxuan Song and Xinyue Song and Rui Zhao and Hong Ling and Fang He and Meng Zhang and Qiming Pang},
  journal = {Journal of Nanobiotechnology},
  year = {2026},
  month = jun,
  doi = {10.1186/s12951-026-04710-w},
  url = {https://doi.org/10.1186/s12951-026-04710-w},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Enhanced exosome biomanufacturing, precision isolation, and advanced engineering: toward mechanistic regulation and biomaterial integration for osteoarthritis therapy
AU  - Meipei Gao
AU  - Qiaotian Yin
AU  - Zejian Zhong
AU  - Zhuoxuan Song
AU  - Xinyue Song
AU  - Rui Zhao
AU  - Hong Ling
AU  - Fang He
AU  - Meng Zhang
AU  - Qiming Pang
PY  - 2026
DA  - 2026/06/21
JO  - Journal of Nanobiotechnology
DO  - 10.1186/s12951-026-04710-w
UR  - https://doi.org/10.1186/s12951-026-04710-w
AB  - Exosomes (Exos) are nanoscale extracellular vesicles that have gained attention as promising therapeutic agents due to their unique biological attributes, immunomodulatory roles, and potential for targeted drug delivery. This review systematically explores their biological origins, secretion mechanisms, and cellular uptake dynamics of Exos. We explore strategies to enhance Exos production, including genetic modifications and optimized culture conditions, and compare purification methods such as ultracentrifugation and size-exclusion techniques, noting their advantages and disadvantages. Additionally, we discuss the engineering of Exos for drug delivery applications through methods like electroporation and physicochemical modifications. Focusing on osteoarthritis (OA)—a widespread degenerative joint disorder lacking effective clinical treatments for halting its progression or promoting cartilage regeneration—we elaborate on the therapeutic mechanisms of Exos in this context, including regulation of inflammatory responses, enhancement of chondrocyte survival, promotion of matrix synthesis, and inhibition of pathological angiogenesis via bioactive molecules like microRNAs and proteins. To address the challenges of rapid clearance and insufficient targeting in vivo, we propose innovative delivery systems using polymer-based and natural biomaterials to improve Exos retention and stability within the joint cavity. This approach aims to optimize therapeutic outcomes and bridge fundamental biological research with clinical applications, advancing next-generation OA treatment strategies.  Graphical abstract:
SN  - 1477-3155
ER  -