Self-powered triboelectric-responsive microneedles with controllable release of optogenetically engineered extracellular vesicles for intervertebral disc degeneration repair

Weifeng Zhang, Xuan Qin, Gaocai Li, Xingyu Zhou, Hongyang Li, Di Wu, Yu Song, Kangcheng Zhao, Kun Wang, Xiaobo Feng, Lei Tan, Bingjin Wang (), Xuhui Sun (), Zhen Wen () and Cao Yang ()
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Weifeng Zhang: Huazhong University of Science and Technology
Xuan Qin: Soochow University
Gaocai Li: Huazhong University of Science and Technology
Xingyu Zhou: Huazhong University of Science and Technology
Hongyang Li: Soochow University
Di Wu: Huazhong University of Science and Technology
Yu Song: Huazhong University of Science and Technology
Kangcheng Zhao: Huazhong University of Science and Technology
Kun Wang: Huazhong University of Science and Technology
Xiaobo Feng: Huazhong University of Science and Technology
Lei Tan: Huazhong University of Science and Technology
Bingjin Wang: Huazhong University of Science and Technology
Xuhui Sun: Soochow University
Zhen Wen: Soochow University
Cao Yang: Huazhong University of Science and Technology

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Excessive exercise is an etiological factor of intervertebral disc degeneration (IVDD). Engineered extracellular vesicles (EVs) exhibit excellent therapeutic potential for disease-modifying treatments. Herein, we fabricate an exercise self-powered triboelectric-responsive microneedle (MN) assay with the sustainable release of optogenetically engineered EVs for IVDD repair. Mechanically, exercise promotes cytosolic DNA sensing-mediated inflammatory activation in senescent nucleus pulposus (NP) cells (the master cell population for IVD homeostasis maintenance), which accelerates IVDD. TREX1 serves as a crucial nuclease, and disassembly of TRAM1-TREX1 complex disrupts the subcellular localization of TREX1, triggering TREX1-dependent genomic DNA damage during NP cell senescence. Optogenetically engineered EVs deliver TRAM1 protein into senescent NP cells, which effectively reconstructs the elimination function of TREX1. Triboelectric nanogenerator (TENG) harvests mechanical energy and triggers the controllable release of engineered EVs. Notably, an optogenetically engineered EV-based targeting treatment strategy is used for the treatment of IVDD, showing promising clinical potential for the treatment of degeneration-associated disorders.

Date: 2024
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DOI: 10.1038/s41467-024-50045-1

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