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.

Efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains challenging. Here, the authors fabricate a minimally invasive microneedle device, which provides efficient and sustained extracellular vesicle delivery for spinal cord injury treatment.

Details

Title
Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury
Author
Fang, Ao 1 ; Wang, Yifan 2 ; Guan, Naiyu 1 ; Zuo, Yanming 3 ; Lin, Lingmin 4   VIAFID ORCID Logo  ; Guo, Binjie 4 ; Mo, Aisheng 4 ; Wu, Yile 4 ; Lin, Xurong 4 ; Cai, Wanxiong 4 ; Chen, Xiangfeng 5 ; Ye, Jingjia 5 ; Abdelrahman, Zeinab 1 ; Li, Xiaodan 1 ; Zheng, Hanyu 4 ; Wu, Zhonghan 4 ; Jin, Shuang 4 ; Xu, Kan 6 ; Huang, Yan 7 ; Gu, Xiaosong 8 ; Yu, Bin 8 ; Wang, Xuhua 9   VIAFID ORCID Logo 

1  Zhejiang University School of Medicine, Department of Rehabilitation Medicine of First Affiliated Hospital and School of Brain Science and Brain Medicine, Hangzhou, P. R. China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, NHC and CAMS Key Laboratory of Medical Neurobiology, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Department of Orthopedics of 2nd Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, PR China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
2  Zhejiang University School of Medicine, Department of Rehabilitation Medicine of First Affiliated Hospital and School of Brain Science and Brain Medicine, Hangzhou, P. R. China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Department of Orthopedics of 2nd Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, PR China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
3  Zhejiang University School of Medicine, Department of Rehabilitation Medicine of First Affiliated Hospital and School of Brain Science and Brain Medicine, Hangzhou, P. R. China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, NHC and CAMS Key Laboratory of Medical Neurobiology, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
4  Zhejiang University, Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, NHC and CAMS Key Laboratory of Medical Neurobiology, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
5  Zhejiang University, Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, NHC and CAMS Key Laboratory of Medical Neurobiology, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Department of Orthopedics of 2nd Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, PR China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
6  Zhejiang University, Department of Orthopedics of 2nd Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, PR China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
7  Medical School of Nantong University, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Nantong, China (GRID:grid.260483.b) (ISNI:0000 0000 9530 8833) 
8  Nantong University, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong, China (GRID:grid.260483.b) (ISNI:0000 0000 9530 8833) 
9  Zhejiang University School of Medicine, Department of Rehabilitation Medicine of First Affiliated Hospital and School of Brain Science and Brain Medicine, Hangzhou, P. R. China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, NHC and CAMS Key Laboratory of Medical Neurobiology, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Zhejiang University, Department of Orthopedics of 2nd Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, PR China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X); Nantong University, Co-innovation Center of Neuroregeneration, Nantong, P. R. China (GRID:grid.260483.b) (ISNI:0000 0000 9530 8833) 
Pages
4011
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-023-39745-2
ProQuest document ID
2834368317
Copyright
© The Author(s) 2023. corrected publication 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.