2. Academic Validation
  3. Local H2 release remodels senescence microenvironment for improved repair of injured bone

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

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. wei.tang1@siat.ac.cn.
  • 6 The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. liucs@ecust.edu.cn.
  • 7 Shanghai Key Laboratory of Hydrogen Science & Center of Hydrogen Science, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China. nanoflower@126.com.
  • 8 Medical Center on Aging, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. nanoflower@126.com.
  • 9 Shenzhen Research Institute, Shanghai Jiao Tong University, Shenzhen, 518057, China. nanoflower@126.com.
  • # 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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