2. Academic Validation
  3. Remodeling the Proinflammatory Microenvironment in Osteoarthritis through Interleukin-1 Beta Tailored Exosome Cargo for Inflammatory Regulation and Cartilage Regeneration

Remodeling the Proinflammatory Microenvironment in Osteoarthritis through Interleukin-1 Beta Tailored Exosome Cargo for Inflammatory Regulation and Cartilage Regeneration

  • ACS Nano. 2025 Feb 4;19(4):4924-4941. doi: 10.1021/acsnano.4c16785.
Manyu Chen 1,  Yuhan Liu 2,  Yi Cao 1,  Chengkun Zhao 1,  Quanying Liu 3,  Na Li 1 4,  Yuan Liu 5,  Xiaolin Cui 6 7,  Pengcheng Liu 8,  Jie Liang 1 4,  Yujiang Fan 1,  Qiguang Wang 1,  Xingdong Zhang 1
Affiliations

Affiliations

  • 1 National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China.
  • 2 The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China.
  • 3 Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University (Army Medical University), Chongqing 400038, China.
  • 4 Sichuan Testing Center for Biomaterials and Medical Devices, Sichuan University, 29 Wangjiang Road, Chengdu 610000, China.
  • 5 Orthopedics Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.
  • 6 Cardiac and Osteochondral Tissue Engineering (COTE) Group, School of medicine, the Chinese University of Hong Kong, Shenzhen 518172, China.
  • 7 Department of Orthopedic Surgery & Musculoskeletal Medicine, Centre for Bioengineering & Nanomedicine, University of Otago, Christchurch 8011, New Zealand.
  • 8 Chengdu Xiangyakanglin Biotechnology Co., Ltd, Chengdu 610213, China.
PMID: 39848926 DOI: 10.1021/acsnano.4c16785
Abstract

Osteoarthritis (OA) presents a significant therapeutic challenge, with few options for preserving joint cartilage and repairing associated tissue damage. Inflammation is a pivotal factor in OA-induced cartilage deterioration and synovial inflammation. Recently, exosomes derived from human umbilical cord mesenchymal stem cells (HucMSCs) have gained recognition as a promising noncellular therapeutic modality, but their use is hindered by the challenge of harvesting a sufficient number of exosomes with effective therapeutic efficacy. Given that HucMSCs are highly sensitive to microenvironmental signals, we hypothesized that priming HucMSCs within a proinflammatory environment would increase the number of exosomes secreted with enhanced anti-inflammatory properties. Subsequent miRNA profiling and pathway analysis confirmed that interleukin-1 beta (IL-1β)-induced exosomes (C-Exos) exert positive effects through miRNA regulation and signaling pathway modulation. In vitro experiments revealed that C-Exos enhance chondrocyte functionality and cartilage matrix production, as well as macrophage polarization, thereby enhancing cartilage repair. C-Exos were encapsulated in hyaluronic acid hydrogel microspheres (HMs) to ensure sustained release, leading to substantial improvements in the inflammatory microenvironment and cartilage regeneration in a rat OA model. This study outlines a strategy to tailor exosome cargo for anti-inflammatory and cartilage regenerative purposes, with the functionalized HMs demonstrating potential for OA treatment.

Keywords

IL-1β-tailor exosome cargo; MSC-derived exosome; cartilage regeneration; inflammation regulatory; osteoarthritis therapy.

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