2. Academic Validation
  3. Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury

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

  • Nat Commun. 2023 Jul 7;14(1):4011. doi: 10.1038/s41467-023-39745-2.
Ao Fang # 1 2 3 4,  Yifan Wang # 1 4,  Naiyu Guan # 1 2 3 4,  Yanming Zuo # 1 2 3,  Lingmin Lin 2 3,  Binjie Guo 2 3,  Aisheng Mo 2 3,  Yile Wu 2 3,  Xurong Lin 2 3,  Wanxiong Cai 2 3,  Xiangfeng Chen 2 3 4,  Jingjia Ye 2 3 4,  Zeinab Abdelrahman 1 2 3 4,  Xiaodan Li 1 2 3 4,  Hanyu Zheng 2 3,  Zhonghan Wu 2 3,  Shuang Jin 2 3,  Kan Xu 4,  Yan Huang 5,  Xiaosong Gu 6,  Bin Yu 6,  Xuhua Wang 7 8 9 10 11
Affiliations

Affiliations

  • 1 Department of Rehabilitation Medicine of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, 310003, Hangzhou, Zhejiang Province, P. R. China.
  • 2 Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, 1369 West Wenyi Road, 311121, Hangzhou, China.
  • 3 NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 310058, Hangzhou, China.
  • 4 Department of Orthopedics of 2nd Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Zhejiang University, 310003, Hangzhou, Zhejiang Province, PR China.
  • 5 Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, 226001, Nantong, China.
  • 6 Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, China.
  • 7 Department of Rehabilitation Medicine of First Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, 310003, Hangzhou, Zhejiang Province, P. R. China. xhw@zju.edu.cn.
  • 8 Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, 1369 West Wenyi Road, 311121, Hangzhou, China. xhw@zju.edu.cn.
  • 9 NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, 310058, Hangzhou, China. xhw@zju.edu.cn.
  • 10 Department of Orthopedics of 2nd Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Zhejiang University, 310003, Hangzhou, Zhejiang Province, PR China. xhw@zju.edu.cn.
  • 11 Co-innovation Center of Neuroregeneration, Nantong University, 226001, Nantong, Jiangsu, P. R. China. xhw@zju.edu.cn.
  • # Contributed equally.
PMID: 37419902 DOI: 10.1038/s41467-023-39745-2
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.

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