Local H2 release remodels senescence microenvironment for improved repair of injured bone

  • Nat Commun. 2023 Nov 27;14(1):7783. doi: 10.1038/s41467-023-43618-z.
Shengqiang Chen  #  1  2 ,  Yuanman Yu  #  3 ,  Songqing Xie  #  1 ,  Danna Liang  4 ,  Wei Shi  1 ,  Sizhen Chen  1 ,  Guanglin Li  1 ,  Wei Tang  5 ,  Changsheng Liu  6 ,  Qianjun He  7  8  9
Affiliations
  • 1. Key Laboratory of Human-Machine-Intelligence Synergic System, Research Center for Neural Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, Guangdong, China.
  • 2. Shanghai Key Laboratory of Hydrogen Science & Center of Hydrogen Science, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 3. The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
  • 4. Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China.
  • 5. Key Laboratory of Human-Machine-Intelligence Synergic System, Research Center for Neural Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, Guangdong, China. [email protected].
  • 6. The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. [email protected].
  • 7. Shanghai Key Laboratory of Hydrogen Science & Center of Hydrogen Science, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China. [email protected].
  • 8. Medical Center on Aging, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. [email protected].
  • 9. Shenzhen Research Institute, Shanghai Jiao Tong University, Shenzhen, 518057, China. [email protected].
  • # Contributed equally.
PMID: 38012166 DOI: 10.1038/s41467-023-43618-z
Abstract

The senescence microenvironment, which causes persistent inflammation and loss of intrinsic regenerative abilities, is a main obstacle to effective tissue repair in elderly individuals. In this work, we find that local H2 supply can remodel the senescence microenvironment by anti-inflammation and anti-senescence effects in various senescent cells from skeletally mature bone. We construct a H2-releasing scaffold which can release high-dosage H2 (911 mL/g, up to 1 week) by electrospraying polyhydroxyalkanoate-encapsulated CaSi2 nanoparticles onto mesoporous bioactive glass. We demonstrate efficient remodeling of the microenvironment and enhanced repair of critical-size bone defects in an aged mouse model. Mechanistically, we reveal that local H2 release alters the microenvironment from pro-inflammation to anti-inflammation by senescent macrophages repolarization and secretome change. We also show that H2 alleviates the progression of aging/injury-superposed senescence, facilitates the recruitment of endogenous cells and the preservation of their regeneration capability, thereby creating a pro-regenerative microenvironment able to support bone defect regeneration.

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