DNA-adsorbing nanozyme hydrogel reprograms the immuno-oxidative microenvironment to support stem cell-based cartilage repair in osteoarthritis.
6 affiliations
- 1Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
- 2Institute of Orthopedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
- 3Department of Spine Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
- 4Department of Orthopedics, Huainan Xinhua Hospital Affiliated to Anhui University of Science and Technology, Huainan, 232000, China.
- 5Department of Orthopedics, People's Hospital of Wuhe County, Bengbu, 233699, China.
- 6Orthopaedic Research Institute, Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, 610041, China.
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.
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BibTeX
@article{yu2026dnaadsorbing,
title = {{DNA-adsorbing nanozyme hydrogel reprograms the immuno-oxidative microenvironment to support stem cell-based cartilage repair in osteoarthritis.}},
author = {Haoran Yu and Zhongyao Hu and Qiwei Tan and Chen Wang and Bo Wang and Yiqun Yan and Yangmang Yu and Fei Zhang and Mingjun Zhang and Yao Huang and Dechao Cai and Yue Wang and Hao Zhou and Duan Wang and Wendan Cheng},
journal = {Bioactive materials},
year = {2026},
month = oct,
doi = {10.1016/j.bioactmat.2026.09.043},
url = {https://europepmc.org/article/MED/42899179},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - DNA-adsorbing nanozyme hydrogel reprograms the immuno-oxidative microenvironment to support stem cell-based cartilage repair in osteoarthritis.
AU - Haoran Yu
AU - Zhongyao Hu
AU - Qiwei Tan
AU - Chen Wang
AU - Bo Wang
AU - Yiqun Yan
AU - Yangmang Yu
AU - Fei Zhang
AU - Mingjun Zhang
AU - Yao Huang
AU - Dechao Cai
AU - Yue Wang
AU - Hao Zhou
AU - Duan Wang
AU - Wendan Cheng
PY - 2026
DA - 2026/10/11
JO - Bioactive materials
DO - 10.1016/j.bioactmat.2026.09.043
UR - https://europepmc.org/article/MED/42899179
AB - 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.
SN - 2452-199X
ER -