2. Academic Validation
  3. Zwitterionic Brush-Grafted Interfacial Bio-Lubricant Evades Complement C3-Mediated Macrophage Phagocytosis for Osteoarthritis Therapy

Zwitterionic Brush-Grafted Interfacial Bio-Lubricant Evades Complement C3-Mediated Macrophage Phagocytosis for Osteoarthritis Therapy

  • Adv Mater. 2025 Jul;37(28):e2501137. doi: 10.1002/adma.202501137.
Chuandong Cai 1,  Mingwei Wang 2 3,  Luman Wang 1 4,  Jiangtao Guo 2,  Lipeng Wang 1,  Yingkai Zhang 1,  Guohao Wu 1,  Bingxuan Hua 1,  Martien A Cohen Stuart 2 5,  Xuhong Guo 2 6,  Lu Cao 1,  Zuoqin Yan 1 7
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, Zhongshan Hospital, Institute of Bone and Joint Diseases, Fudan University, Shanghai, 200032, China.
  • 2 School of Chemical Engineering, State-Key Laboratory of Chemical Engineering and Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China.
  • 3 Department of Dentistry-Regenerative Biomaterials, Radboud University Medical Center, Nijmegen, 6525 EX, The Netherlands.
  • 4 Department of Immunology, School of Basic Medical Sciences, Shanghai Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
  • 5 Physical Chemistry and Soft Matter, Wageningen University and Research, Wageningen, 6708 WE, The Netherlands.
  • 6 Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, 410205, China.
  • 7 Department of Orthopaedic Surgery, Shanghai Geriatric Medical Center, 2560 Chunshen Road, Shanghai, 201104, China.
PMID: 40304130 DOI: 10.1002/adma.202501137
Abstract

Administering a bio-lubricant is a promising therapeutic approach for the treatment of osteoarthritis (OA), in particular, if it can both manage symptoms and halt disease progression. However, the clearance of these bio-lubricants mediated by synovial macrophages leads to reduced therapeutic efficiency and adverse inflammatory responses. Herein, it is shown that this process is predominantly mediated by the specific binding of complement C3 (on nanoparticle) and CD11b (on macrophage). More importantly, through a systematic evaluation of various interface modifications, a macrophage-evading nanoparticle strategy is proposed, which not only minimizes friction, but also largely suppresses C3 adsorption. It involves employing a zwitterionic poly-2-methacryloyloxyethyl phosphorylcholine (PMPC) brush layer grafted from a crosslinked gelatin core. In vitro studies demonstrate that such a nanoparticle lubricant can evade macrophage phagocytosis and further prevent the pro-inflammatory M1 polarization and subsequent harmful release of cytokines. In vivo studies show that the designed PMPC brush layer effectively mitigates synovial inflammation, alleviates OA-associated pain, and protects cartilage from degeneration, thus preventing OA progression. These findings clarify the pivotal role of complement C3-mediated macrophage recognition in nanoparticles clearance and offer a promising nanoparticle design strategy to restore joint lubrication.

Keywords

complement C3; interface; macrophages; osteoarthritis; phagocytosis.

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