Signal Converter-Based Therapy Platform Promoting Aging Bone Healing by Improving Permeability of the Mitochondrial Membrane

IF 27.4 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Advanced Materials Pub Date : 2025-04-28 DOI:10.1002/adma.202500156

Yiyang Huang, Jiannan Mao, Ziang Li, Wenbo Wang, Zhengxia Ni, Feng Cai, Jincheng Tang, Wei Wang, Lichen Zhang, Liang Zhou, Xinzhao Jiang, Jie Wu, Qiangqiang Guo, Min Rui, Ziyan Huang, Haochen Jiang, Lingjun Wang, Kun Xi, Yong Gu, Liang Chen

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Abstract

The aging microenvironment promotes persistent inflammation and loss of intrinsic regenerative capacity. These are major obstacles to effective bone tissue repair in older adults. This study aims to explore how physical thermal stimulation can effectively delay the bone marrow mesenchymal stem cells (BMSCs) aging process. Based on this, an implantable physical signal-converter platform is designed as a therapeutic system that enables stable heat signals at the bone injury site under ultrasound stimulation (US). It is found that the therapeutic platform controllably reduces the mitochondrial outer membrane permeabilization of aging BMSCs, bidirectionally inhibiting mitochondrial reactive oxygen species and mitochondrial DNA (mtDNA) leakage. The leakage ratio of mtDNA decreases by 22.7%. This effectively mitigates the activation of the cGAS-STING pathway and its downstream NF-κB signaling induced by oxidative stress in aging BMSCs, thereby attenuating the pathological advancement of chronic inflammation. Thus, it effectively restores the metabolism and osteogenic differentiation of aging BMSCs in vitro, which is further confirmed in a rat model. In the GMPG/US group, the bone mineral density increases 2–3 times at 4 weeks in the rats femoral defect model. Therefore, this ultrasound-based signal-conversion platform provides a promising strategy for aging bone defect repair.

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基于信号转换器的治疗平台通过提高线粒体膜的通透性促进老化骨愈合

衰老的微环境促进了持续的炎症和内在再生能力的丧失。这些是老年人有效修复骨组织的主要障碍。本研究旨在探讨物理热刺激如何有效延缓骨髓间充质干细胞（BMSCs）的衰老过程。基于此，设计了一种可植入的物理信号转换器平台，作为超声刺激下骨损伤部位稳定热信号的治疗系统（US）。发现该治疗平台可控制地降低衰老骨髓间充质干细胞线粒体外膜通透性，双向抑制线粒体活性氧和线粒体DNA （mtDNA）渗漏。mtDNA的漏出率降低22.7%。这有效减轻了老化骨髓间充质干细胞氧化应激诱导的cGAS-STING通路及其下游NF-κB信号的激活，从而减缓了慢性炎症的病理进展。因此，在体外有效恢复衰老骨髓间充质干细胞的代谢和成骨分化，这在大鼠模型中得到进一步证实。GMPG/US组大鼠股骨缺损模型4周时骨密度增加2 ~ 3倍。因此，这种基于超声的信号转换平台为老化骨缺损修复提供了一种很有前景的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advanced Materials 工程技术-材料科学：综合

CiteScore

43.00

自引率

4.10%

发文量

2182

审稿时长

2 months

期刊介绍： Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.