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

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.

Reactive oxygen species-scavenging nanomaterials for the prevention and treatment of age-related diseases

“…Polyhydroxyalkanoate-encapsulated CaSi2 nanoparticles (CSN)-loading mesoporous bioactive glass (MBG) scaffolds (CSN@PHA-MBG) were designed for releasing H 2 in the repair of bone defect of elders [ 192 ]. CSN greatly improved H 2 release capacity for approximately one week.…”

Gases and gas-releasing materials for the treatment of chronic diabetic wounds

“…At present, hydrogen, hydrogen-rich water (HRW), and hydrogen-rich brine (HRS) are mainly used for wound repair. 141–143 However, hydrogen is difficult to penetrate into tissues due to its explosive and low solubility, 44,144 and its safety and effectiveness when used need to be further studied. At present, there are few studies on H 2 carriers applied to diabetic wounds, so it is urgent to develop a treatment program that can deliver hydrogen continuously to treat diabetic wounds.…”

Multifunctional biomimetic hydrogel dressing provides anti-infection treatment and improves immunotherapy by reprogramming the infection-related wound microenvironment

“…Nonetheless, its clinical application has been inherently constrained by its low bioavailability [ 26 , 27 ]. Mesoporous bioactive glass (MBG), a third-generation biomaterial, has attracted significant interest in the nanomaterials arena, credited to its unique attributes including extraordinary tissue regeneration and exceptional stability [ 28 – 30 ]. This class of materials modifies the extracellular matrix milieu by generating solubilization and degradation products that effectuate specific biological activities.…”