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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.

SUBMITTER: Chen S

PROVIDER: S-EPMC10682449 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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

Chen Shengqiang S Yu Yuanman Y Xie Songqing S Liang Danna D Shi Wei W Chen Sizhen S Li Guanglin G Tang Wei W Liu Changsheng C He Qianjun Q

Nature communications 20231127 1

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 ...[more]

PMID: 38012166

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Project description:Chronic diabetic wounds present significant treatment challenges due to their complex microenvironment, often leading to suboptimal healing outcomes. Hydrogen sulfide (H2S), a crucial gaseous signaling molecule, has shown great potential in modulating inflammation, oxidative stress and extracellular matrix remodeling, which are essential for effective wound healing. However, conventional H2S delivery systems lack the adaptability required to meet the dynamic demands of different healing stages, thereby limiting their therapeutic efficacy. To address this, we developed an injectable, ROS-responsive H2S donor system integrated within a gelatin methacryloyl (GelMA) hydrogel matrix, forming a double-network hydrogel (GelMA-ODex@RRHD). The injectability of this hydrogel allows for minimally invasive application, conforming closely to wound contours and ensuring uniform distribution. The incorporation of oxidatively modified dextran derivatives (ODex) not only preserves biocompatibility but also enables the chemical attachment of ROS-responsive H2S donors. The GelMA-ODex@RRHD hydrogel releases H2S in response to oxidative stress, optimizing the environment for cell growth, modulating macrophage polarization and supporting vascular regeneration. This innovative material effectively suppresses inflammation during the initial phase, promotes tissue regeneration in the proliferative phase and facilitates controlled matrix remodeling in later stages, ultimately enhancing wound closure and functional recovery. The H2S released by GelMA-ODex@RRHD not only expedited the process of wound healing but also improved the biomechanical characteristics of newborn skin in diabetic mice, particularly in terms of stiffness and elasticity. This enhancement resulted in the skin quality being more similar to normal skin during the wound healing process. By aligning therapeutic delivery with the natural healing process, this approach offers a promising pathway toward more effective and personalized treatments for chronic diabetic wounds.

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

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Local H<sub>2</sub> release remodels senescence microenvironment for improved repair of injured bone.

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

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Local H&lt;sub&gt;2&lt;/sub&gt; release remodels senescence microenvironment for improved repair of injured bone.

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OmicsDI is part of the ELIXIR infrastructure

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

Local H<sub>2</sub> release remodels senescence microenvironment for improved repair of injured bone.