{
  "abstract": "Effective prophylactic interventions for exercise-induced joint damage and preclinical osteoarthritis remain elusive, as abnormal mechanical loading drives pathology through a dual pyroptotic loop between chondrocytes and macrophages. We present PMUC, a mechano-responsive lubricating hydrogel engineered for graded joint protection and repair. Mimicking native lubrication, intra-articular PMUC forms a persistent hydration layer that dissipates mechanical stress. Under pathological load, stress-induced reactive oxygen species trigger mannose and nanocomplex release. This cascade activates the hexosamine biosynthetic pathway, suppressing Caspase-3/GSDME-mediated chondrocyte pyroptosis while concurrently reprogramming macrophage-derived extracellular vesicles. Enriched with XIAP and OTULIN proteins, these in situ-generated extracellular vesicles act as intercellular messengers that disrupt the inflammatory cycle and facilitate matrix regeneration. In preclinical rat models of high-load exercise and post-traumatic OA, PMUC prevents cartilage erosion and achieves full regeneration with restored locomotion within eight weeks. Here we show that PMUC integrates adaptive lubrication with stress-triggered immune-metabolic modulation, offering a first‑in‑class strategy to protect joints and alleviate early OA.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China",
    "Department of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China",
    "Department of Orthopedics, State Key Laboratory of Immune Response and Immunotherapy, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China",
    "Department of Orthopedics, The First Affiliated Hospital of Anhui University of Science and Technology, Huainan, China",
    "Department of Sports Medicine, State Key Laboratory of Frigid Zone Cardiovascular Diseases, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Guangdong Provincial Key Laboratory of Speed Capability, The First Affiliated Hospital, Jinan University, Guangzhou, China",
    "Department of Orthopedics, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China",
    "Department of Geriatric, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China",
    "Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xudong Zhang",
      "orcid": "0009-0004-7203-8427"
    },
    {
      "affs": [
        3
      ],
      "name": "Wei Zhu"
    },
    {
      "affs": [
        4
      ],
      "name": "Huajun Wang"
    },
    {
      "affs": [
        5
      ],
      "name": "Yingjie Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Ziheng Bu"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Junchao Huang"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiawei Mei"
    },
    {
      "affs": [
        2
      ],
      "name": "Quan Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiachang Hong"
    },
    {
      "affs": [
        1
      ],
      "name": "Jianing Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "JinXi An"
    },
    {
      "affs": [
        6
      ],
      "name": "Sudan Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Chen Zhu"
    },
    {
      "affs": [
        7
      ],
      "name": "Wanbo Zhu",
      "orcid": "0000-0003-3457-3432"
    },
    {
      "affs": [
        0
      ],
      "name": "Peng Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9psewg3b8htrb.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77833-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696705/",
  "id": "9psewg3b8htrb",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-77833-1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
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  ],
  "openalex": "W7214220177",
  "pdf_url": "https://europepmc.org/articles/PMC13696705?pdf=render",
  "pmcid": "PMC13696705",
  "pmid": "42928352",
  "published": "2026-09-24",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/9psewg3b8htrb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:01Z",
      "native_id": "PMC13696705",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41467-026-77833-1"
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    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928352",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928352"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
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  ],
  "title": "Multimodal hydrogel modulation of extracellular vesicle cargo to arrest post-traumatic osteoarthritis in murine models",
  "title_text": "Multimodal hydrogel modulation of extracellular vesicle cargo to arrest post-traumatic osteoarthritis in murine models",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:00Z",
  "url": "https://research.draconitic.com/paper/9psewg3b8htrb",
  "venue": "Nature Communications",
  "versions": []
}