MicroSphere 3D Structures Delay Tissue Senescence through Mechanotransduction.

Ziang Li, Jincheng Tang, Liang Zhou, Jiannan Mao, Wei Wang, Ziyan Huang, Lichen Zhang, Jie Wu, Xinzhao Jiang, Zhouye Ding, Kun Xi, Feng Cai, Yong Gu, Liang Chen

Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Soochow, Jiangsu 215000, China.Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Soochow, Jiangsu 215000, China. · pubmed

Paper

Abstract

The extracellular matrix (ECM) stores signaling molecules and facilitates mechanical and biochemical signaling in cells. However, the influence of biomimetic "rejuvenation" ECM structures on aging- and degeneration-related cellular activities and tissue repair is not well understood. We combined physical extrusion and precise "on-off" alternating cross-linking methods to create anisotropic biomaterial microgels (MicroRod and MicroSphere) and explored how they regulate the cell activities of the nucleus pulposus (NP) and their potential antidegenerative effects on intervertebral discs. NP cells exhibited aligned growth along the surface of the MicroRod, enhanced proliferation, and reduced apoptosis. This suggests an adaptive cellular response involving adhesion and mechanosensing, which causes cytoskeletal extension via environmental cues. NP cells maintain nuclear membrane integrity through the YAP/TAZ pathway, which activates the cGAS-STING pathway to rectify the aging mechanisms. In vivo, MicroRod carries NP cells and reduces inflammatory factor and protease secretion in degenerated intervertebral discs, inhibiting degeneration and promoting NP tissue regeneration. Our findings highlight the role of mechanical stress in maintaining cellular activity and antiaging effects in harsh environments, providing a foundation for further research and development of antidegenerative biomaterials.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper explores the role of biomimetic extracellular matrix structures in delaying tissue senescence and promoting regeneration, which aligns with longevity research by addressing mechanisms that contribute to aging and degeneration. However, while the findings are solid and contribute to the understanding of mechanotransduction in cellular activities, the impact is limited as it primarily focuses on a specific application in intervertebral discs rather than broader implications for aging or lifespan extension.

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