Local H<sub>2</sub> release remodels senescence microenvironment for improved repair of injured bone.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38012166.
- Also identified by DOI 10.1038/s41467-023-43618-z and PMC identifier 10682449.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 H<sub>2</sub> supply can remodel the senescence microenvironment by anti-inflammation and anti-senescence effects in various senescent cells from skeletally mature bone. We construct a H<sub>2</sub>-releasing scaffold which can release high-dosage H<sub>2</sub> (911 mL/g, up to 1 week) by electrospraying polyhydroxyalkanoate-encapsulated CaSi<sub>2</sub> 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 H<sub>2</sub> release alters the microenvironment from pro-inflammation to anti-inflammation by senescent macrophages repolarization and secretome change. We also show that H<sub>2</sub> 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.
Medical subject headings
- Cellular Senescence
- Bone and Bones