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Peer-reviewedCC BY-NC-NDBioactive Materials

Injectable bioactive glass hydrogels orchestrate metalloimmunotherapy by depleting pathogenic B cells and rescuing bone in rheumatoid arthritis

  • Ziwei Yan1
  • Yue Chen1
  • Fanrui Zeng1
  • Qing Chen2
  • Hanjia Cai2
  • Ran Qin3
  • JunYi Xu2
  • Bingjie Gu4
  • Laikui Liu1
  • Usanee Pantulap5
  • Kai Zheng
  • Wen Sun
5 affiliations
  1. 1Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210029, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, 210029, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases (Nanjing Medical University), Nanjing, 210029, China
  2. 2Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210029, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases (Nanjing Medical University), Nanjing, 210029, China
  3. 3Department of Sports Medicine and Joint Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
  4. 4Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing, Medical University, Nanjing, China
  5. 5Department of Science Service, Ministry of Higher Education, Science, Research and Innovation, Bangkok, 10400, Thailand
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Abstract

Rheumatoid arthritis (RA) is characterized by persistent synovial inflammation and progressive bone destruction. Transcriptomic profiling identified hyperactivated B cells as key contributors to osteoimmune dysregulation, supporting localized B cell intervention as a therapeutic strategy. Here, an injectable thermosensitive hydroxypropyl chitin hydrogel incorporating Cu/Zn-doped bioactive glass particles, termed BG@HPCH, was developed for localized metalloimmunotherapy. BG incorporation improved the shear-thinning behavior, thermosensitive gelation, storage modulus, and stability of the hydrogel. In vitro, ionic release from BG@HPCH selectively reduced pathogenic B cell survival while preserving mesenchymal stem cell (MSC) viability. The optimized M-BG@HPCH increased the B cell dead-cell area from 1.93 ± 0.48% to 91.12 ± 0.90% at 24 h, while maintaining MSC viability at 98.59 ± 0.26% after 3 days. In TNF-transgenic mice, a single intra-articular injection of BG@HPCH reduced arthritis index scores from 2.88 ± 0.18 to 1.81 ± 0.13 at day 28, limited bone erosion, and showed no detectable systemic toxicity. Micro-CT analysis showed improved bone preservation, with BV/TV increasing from 30.00 ± 6.74% to 55.66 ± 1.07%. OCN staining further confirmed enhanced osteogenic activity, with the OCN + area increasing by 2.16 times. Flow cytometry confirmed reduced B220 + CD45.2 + B cell accumulation in treated joints. Single-cell RNA sequencing of 23,921 joint cells showed that BG@HPCH reduced inflammatory B cell, macrophage, and fibroblast subsets while expanding osteoblast-associated regenerative populations, accompanied by suppression of CD23 − and CD74-associated B cell signaling axes. These findings establish BG@HPCH as a localized immunoregenerative biomaterial for coordinating pathogenic B cell depletion and bone repair in RA.

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Cite

BibTeXRIS
BibTeX
@article{yan2026injectable,
  title = {{Injectable bioactive glass hydrogels orchestrate metalloimmunotherapy by depleting pathogenic B cells and rescuing bone in rheumatoid arthritis}},
  author = {Ziwei Yan and Yue Chen and Fanrui Zeng and Qing Chen and Hanjia Cai and Ran Qin and JunYi Xu and Bingjie Gu and Laikui Liu and Usanee Pantulap and Kai Zheng and Wen Sun},
  journal = {Bioactive Materials},
  year = {2026},
  month = oct,
  doi = {10.1016/j.bioactmat.2026.08.057},
  url = {https://doi.org/10.1016/j.bioactmat.2026.08.057},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Injectable bioactive glass hydrogels orchestrate metalloimmunotherapy by depleting pathogenic B cells and rescuing bone in rheumatoid arthritis
AU  - Ziwei Yan
AU  - Yue Chen
AU  - Fanrui Zeng
AU  - Qing Chen
AU  - Hanjia Cai
AU  - Ran Qin
AU  - JunYi Xu
AU  - Bingjie Gu
AU  - Laikui Liu
AU  - Usanee Pantulap
AU  - Kai Zheng
AU  - Wen Sun
PY  - 2026
DA  - 2026/10/23
JO  - Bioactive Materials
DO  - 10.1016/j.bioactmat.2026.08.057
UR  - https://doi.org/10.1016/j.bioactmat.2026.08.057
AB  - Rheumatoid arthritis (RA) is characterized by persistent synovial inflammation and progressive bone destruction. Transcriptomic profiling identified hyperactivated B cells as key contributors to osteoimmune dysregulation, supporting localized B cell intervention as a therapeutic strategy. Here, an injectable thermosensitive hydroxypropyl chitin hydrogel incorporating Cu/Zn-doped bioactive glass particles, termed BG@HPCH, was developed for localized metalloimmunotherapy. BG incorporation improved the shear-thinning behavior, thermosensitive gelation, storage modulus, and stability of the hydrogel. In vitro, ionic release from BG@HPCH selectively reduced pathogenic B cell survival while preserving mesenchymal stem cell (MSC) viability. The optimized M-BG@HPCH increased the B cell dead-cell area from 1.93 ± 0.48% to 91.12 ± 0.90% at 24 h, while maintaining MSC viability at 98.59 ± 0.26% after 3 days. In TNF-transgenic mice, a single intra-articular injection of BG@HPCH reduced arthritis index scores from 2.88 ± 0.18 to 1.81 ± 0.13 at day 28, limited bone erosion, and showed no detectable systemic toxicity. Micro-CT analysis showed improved bone preservation, with BV/TV increasing from 30.00 ± 6.74% to 55.66 ± 1.07%. OCN staining further confirmed enhanced osteogenic activity, with the OCN + area increasing by 2.16 times. Flow cytometry confirmed reduced B220 + CD45.2 + B cell accumulation in treated joints. Single-cell RNA sequencing of 23,921 joint cells showed that BG@HPCH reduced inflammatory B cell, macrophage, and fibroblast subsets while expanding osteoblast-associated regenerative populations, accompanied by suppression of CD23 − and CD74-associated B cell signaling axes. These findings establish BG@HPCH as a localized immunoregenerative biomaterial for coordinating pathogenic B cell depletion and bone repair in RA.
SN  - 2452-199X
ER  -