Pyroptosis-responsive microspheres modulate the inflammatory microenvironment to retard osteoporosis in female mice
The treatment of osteoporosis and related bone defects remains challenging. This study identifies pyroptosis-driven inflammation as a key disruptor of bone homeostasis. To address this, we develop a magnesium-gelatin composite microsphere scaffold (GelMa/Mg/DMF MS) that exploit pyroptosis blockade and hydrogen-mediated inflammation regulation for osteoporosis treatment. This porous microsphere scaffold is implanted into bone defects to achieve the sustained release of hydrogen gas, magnesium ions (Mg<sup>2+</sup>), and dimethyl fumarate (DMF). DMF act by activating the nuclear factor erythroid-related factor 2 to prevent osteoblast pyroptosis, and combine with the antioxidant effects of hydrogen, effectively remodel the inflammatory microenvironment and create favorable conditions for the restoration of bone homeostasis. Mg<sup>2+</sup> further expedite bone tissue repair. These results demonstrate that the GelMa/Mg/DMF MS effectively reverse inflammatory microenvironments both in vivo and in vitro, resulting in significant tissue repair. These results suggest the combination of hydrogen therapy and pyroptosis blockade as a potential therapeutic strategy.
Authors
- Zhuorun Song
- Yunfei He (ORCID: https://orcid.org/0000-0001-8682-0293)
- Yuqi Yang (ORCID: https://orcid.org/0000-0002-7830-8238)
- Zhihui Han (ORCID: https://orcid.org/0009-0006-4836-1683)
- Liang Cheng (ORCID: https://orcid.org/0000-0001-5324-9094)
- Zengli Zhang (ORCID: https://orcid.org/0000-0002-0108-0263)
- Jun Zou (ORCID: https://orcid.org/0000-0003-0443-3156)
- Zimin Zhang
- Huilin Yang (ORCID: https://orcid.org/0000-0002-9459-7981)
- Fei Gong (ORCID: https://orcid.org/0000-0002-7603-8553)
- Shunyi Lu (ORCID: https://orcid.org/0009-0007-8045-5855)
- Jun Yan Ge (ORCID: https://orcid.org/0000-0001-5503-8899)
- Peng Yang (ORCID: https://orcid.org/0000-0003-1482-1857)
- Guanghui Hou (ORCID: https://orcid.org/0009-0008-8939-1816)
- Jie Cao (ORCID: https://orcid.org/0000-0003-1555-7795)
- Yun Teng
Institutions
- Soochow University (CN)
- First Affiliated Hospital of Soochow University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-30
- DOI
- https://doi.org/10.1038/s41467-025-63456-5
- Citations
- 8
- Primary Topic
- Hydrogen's biological and therapeutic effects
- Type
- article
- Field-Weighted Citation Impact
- 16.05
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Higher Education Discipline Innovation Project
- National Key Research and Development Program of China