{
  "abstract": "Osteoarthritis (OA) is a prevalent degenerative joint disease, and stem cell therapy is often limited by a hostile joint microenvironment. Excessive reactive oxygen species (ROS) and damage-associated cell-free DNA (cfDNA) cooperatively drive innate immune activation, inflammatory macrophage polarization, and chondrogenic instability, forming an immuno-oxidative barrier to cartilage repair. Here, we developed a bioactive DNA-adsorbing nanozyme hydrogel (MNKB/HA) to remodel this niche and enhance BMSC-mediated cartilage repair. MNKB/HA integrates Mn₃O₄ nanozymes with Kartogenin (KGN)-engineered bone marrow mesenchymal stem cells (BMSCs) in an injectable hyaluronic acid matrix. Mn₃O₄ exhibited SOD- and CAT-like activities, scavenging O₂·⁻, H₂O₂, and ·OH, while efficiently adsorbing cfDNA and CpG-ODN to suppress TLR9/MyD88 signaling and M1 polarization and promote M2 polarization. In vitro, 10 μg/mL Mn₃O₄ was cytocompatible, protected BMSCs and chondrocytes from H₂O₂-induced apoptosis, and reshaped inflammatory secretion, with IL-10 increased 8.3-fold and TNF-α, IL-6, and IL-1β reduced. KGN stabilized the chondrogenic phenotype (SOX9, COL Ⅱ, ACAN), while its combination with Mn₃O₄ synergistically enhanced chondrogenic stability under oxidative/inflammatory stress. In rat OA, intra-articular MNKB/HA reduced OARSI scores, restored COL II and ACAN, decreased MMP13, improved subchondral bone microarchitecture, and attenuated synovitis and osteophytes. MNKB/HA also reduced synovial cfDNA, weakened TLR9 signaling, promoted M2 polarization, and showed intra-articular retention for at least 10 days without notable systemic toxicity. Thus, MNKB/HA remodels the immuno-oxidative niche through synergistic ROS scavenging and cfDNA adsorption, providing a strategy for stem cell-mediated cartilage repair in OA.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.",
    "Institute of Orthopedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.",
    "Department of Spine Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.",
    "Department of Orthopedics, Huainan Xinhua Hospital Affiliated to Anhui University of Science and Technology, Huainan, 232000, China.",
    "Department of Orthopedics, People's Hospital of Wuhe County, Bengbu, 233699, China.",
    "Orthopaedic Research Institute, Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, 610041, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Haoran Yu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhongyao Hu"
    },
    {
      "affs": [
        2
      ],
      "name": "Qiwei Tan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chen Wang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Bo Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yiqun Yan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yangmang Yu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Fei Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mingjun Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yao Huang"
    },
    {
      "affs": [
        4
      ],
      "name": "Dechao Cai"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yue Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Hao Zhou"
    },
    {
      "affs": [
        5
      ],
      "name": "Duan Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wendan Cheng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bns0k7npcxynn.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bioactmat.2026.09.043",
  "fulltext_url": "https://europepmc.org/articles/PMC13679311",
  "id": "bns0k7npcxynn",
  "issns": [
    "2452-199X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42899179",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
  ],
  "openalex": "W7221445528",
  "pdf_url": "https://europepmc.org/articles/PMC13679311?pdf=render",
  "pmcid": "PMC13679311",
  "pmid": "42899179",
  "published": "2026-10-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bns0k7npcxynn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42899179",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42899179"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "DNA-adsorbing nanozyme hydrogel reprograms the immuno-oxidative microenvironment to support stem cell-based cartilage repair in osteoarthritis.",
  "title_text": "DNA-adsorbing nanozyme hydrogel reprograms the immuno-oxidative microenvironment to support stem cell-based cartilage repair in osteoarthritis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/bns0k7npcxynn",
  "venue": "Bioactive materials",
  "versions": []
}