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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Cao Yang, 2024. "Self-powered triboelectric-responsive microneedles with controllable release of optogenetically engineered extracellular vesicles for intervertebral disc degeneration repair," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50045-1
    DOI: 10.1038/s41467-024-50045-1
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    References listed on IDEAS

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    1. Akiko Takahashi & Tze Mun Loo & Ryo Okada & Fumitaka Kamachi & Yoshihiro Watanabe & Masahiro Wakita & Sugiko Watanabe & Shimpei Kawamoto & Kenichi Miyata & Glen N. Barber & Naoko Ohtani & Eiji Hara, 2018. "Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Nambin Yim & Seung-Wook Ryu & Kyungsun Choi & Kwang Ryeol Lee & Seunghee Lee & Hojun Choi & Jeongjin Kim & Mohammed R. Shaker & Woong Sun & Ji-Ho Park & Daesoo Kim & Won Do Heo & Chulhee Choi, 2016. "Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein–protein interaction module," Nature Communications, Nature, vol. 7(1), pages 1-9, November.
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