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<p>Chronic hypoxia affects stem cell function during tissue repair. Thus far, the hypoxia-associated impact on periosteal stem cells (PSCs), the main contributor to bone repair, remains unknown, and a tailored oxygen modulation strategy for optimizing PSC function is lacking. Here, PSCs exhibit time-dependent proliferation and survival upon hypoxic exposure and a critical 48-h time-point is identified at which hypoxia transitions from beneficial to detrimental. Then, a photothermal-sensitive coaxial fiber-reinforced membrane containing oxygen and pravastatin is constructed to function as an intelligent oxygen supply system. Leveraging near-infrared light as an ON/OFF switch, the system noninvasively scales up oxygen release beginning 48&#xa0;h post-implantation, counteracting prolonged hypoxia and mitigating its adverse effects on PSCs. The sustained release of pravastatin from the membrane accelerates early neovascularization both directly through its pro-angiogenic effect and indirectly by stimulating vascular endothelial growth factor secretion from PSCs, ensuring a continuous oxygen supply after exogenous oxygen exhaustion. Notably, pravastatin steers PSCs toward robust osteogenic differentiation and provides multifunctional bioactive cues for advanced bone regeneration in vivo. This time-scheduled approach to modulate oxygen supply noninvasively could be applicable beyond bone regeneration for hypoxia-related diseases and multi-tissue repair.</p> Graphical Abstract <p></p>

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A Time-Scheduled Oxygen Modulation System Facilitates Bone Regeneration by Powering Periosteal Stem Cells

  • 期刊论文

  • 发表日期：

    2025年1月28日

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  • Yujie Yang,
  • Xue Gao,
  • Yongfeng Zhang,
  • Shengyou Li,
  • Haining Wu,
  • Bing Xia,
  • Yiming Hao,
  • Beibei Yu,
  • Xueli Gao,
  • Dan Geng,
  • Lingli Guo,
  • Mingze Qin,
  • Yitao Wei,
  • Borui Xue,
  • Shijie Yang,
  • Qi Liu,
  • Shihao Nie,
  • Anhui Qin,
  • Jinya Liu,
  • Lei Lu,
  • Teng Ma,
  • Zhuojing Luo,
  • Jinghui Huang

摘要

Chronic hypoxia affects stem cell function during tissue repair. Thus far, the hypoxia-associated impact on periosteal stem cells (PSCs), the main contributor to bone repair, remains unknown, and a tailored oxygen modulation strategy for optimizing PSC function is lacking. Here, PSCs exhibit time-dependent proliferation and survival upon hypoxic exposure and a critical 48-h time-point is identified at which hypoxia transitions from beneficial to detrimental. Then, a photothermal-sensitive coaxial fiber-reinforced membrane containing oxygen and pravastatin is constructed to function as an intelligent oxygen supply system. Leveraging near-infrared light as an ON/OFF switch, the system noninvasively scales up oxygen release beginning 48 h post-implantation, counteracting prolonged hypoxia and mitigating its adverse effects on PSCs. The sustained release of pravastatin from the membrane accelerates early neovascularization both directly through its pro-angiogenic effect and indirectly by stimulating vascular endothelial growth factor secretion from PSCs, ensuring a continuous oxygen supply after exogenous oxygen exhaustion. Notably, pravastatin steers PSCs toward robust osteogenic differentiation and provides multifunctional bioactive cues for advanced bone regeneration in vivo. This time-scheduled approach to modulate oxygen supply noninvasively could be applicable beyond bone regeneration for hypoxia-related diseases and multi-tissue repair.

Graphical Abstract