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Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury

Author

Listed:
  • Ao Fang

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Yifan Wang

    (Zhejiang University School of Medicine
    Zhejiang University)

  • Naiyu Guan

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Yanming Zuo

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Lingmin Lin

    (Zhejiang University
    Zhejiang University)

  • Binjie Guo

    (Zhejiang University
    Zhejiang University)

  • Aisheng Mo

    (Zhejiang University
    Zhejiang University)

  • Yile Wu

    (Zhejiang University
    Zhejiang University)

  • Xurong Lin

    (Zhejiang University
    Zhejiang University)

  • Wanxiong Cai

    (Zhejiang University
    Zhejiang University)

  • Xiangfeng Chen

    (Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Jingjia Ye

    (Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Zeinab Abdelrahman

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Xiaodan Li

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Hanyu Zheng

    (Zhejiang University
    Zhejiang University)

  • Zhonghan Wu

    (Zhejiang University
    Zhejiang University)

  • Shuang Jin

    (Zhejiang University
    Zhejiang University)

  • Kan Xu

    (Zhejiang University)

  • Yan Huang

    (Medical School of Nantong University)

  • Xiaosong Gu

    (Nantong University)

  • Bin Yu

    (Nantong University)

  • Xuhua Wang

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University
    Zhejiang University)

Abstract

The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains a challenge. Here we present a device for the delivery of extracellular vesicles to treat spinal cord injury. We show that the device incorporating mesenchymal stem cells and porous microneedles enables the delivery of extracellular vesicles. We demonstrate that topical application to the spinal cord lesion beneath the spinal dura, does not damage the lesion. We evaluate the efficacy of our device in a contusive spinal cord injury model and find that it reduces the cavity and scar tissue formation, promotes angiogenesis, and improves survival of nearby tissues and axons. Importantly, the sustained delivery of extracellular vesicles for at least 7 days results in significant functional recovery. Thus, our device provides an efficient and sustained extracellular vesicles delivery platform for spinal cord injury treatment.

Suggested Citation

  • Ao Fang & Yifan Wang & Naiyu Guan & Yanming Zuo & Lingmin Lin & Binjie Guo & Aisheng Mo & Yile Wu & Xurong Lin & Wanxiong Cai & Xiangfeng Chen & Jingjia Ye & Zeinab Abdelrahman & Xiaodan Li & Hanyu Zh, 2023. "Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39745-2
    DOI: 10.1038/s41467-023-39745-2
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    References listed on IDEAS

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    1. Chi Lam Au Yeung & Ngai-Na Co & Tetsushi Tsuruga & Tsz-Lun Yeung & Suet-Ying Kwan & Cecilia S. Leung & Yong Li & Edward S. Lu & Kenny Kwan & Kwong-Kwok Wong & Rosemarie Schmandt & Karen H. Lu & Samuel, 2016. "Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    2. Benedikt Brommer & Miao He & Zicong Zhang & Zhiyun Yang & Jessica C. Page & Junfeng Su & Yu Zhang & Junjie Zhu & Emilia Gouy & Jing Tang & Philip Williams & Wei Dai & Qi Wang & Ryan Solinsky & Bo Chen, 2021. "Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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    Cited by:

    1. Bin Zheng & Qiuya Li & Laiping Fang & Xiaolu Cai & Yan Liu & Yanhong Duo & Bowen Li & Zhengyu Wu & Boxi Shen & Yang Bai & Shi-Xiang Cheng & Xingcai Zhang, 2024. "Microorganism microneedle micro-engine depth drug delivery," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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