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<p>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.</p>

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Pyroptosis-responsive microspheres modulate the inflammatory microenvironment to retard osteoporosis in female mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月30日

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  • Shunyi Lu,
  • Jie Cao,
  • Zhuorun Song,
  • Fei Gong,
  • Peng Yang,
  • Jun Ge,
  • Yunfei He,
  • Zhihui Han,
  • Guanghui Hou,
  • Zimin Zhang,
  • Yuqi Yang,
  • Yun Teng,
  • Zengli Zhang,
  • Jun Zou,
  • Liang Cheng,
  • Huilin Yang

摘要

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 (Mg2+), 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. Mg2+ 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.