A bionic multichannel nanofiber conduit carrying Tubastatin A for repairing injured spinal cord

Shiyang Liao; Yonghang Liu; Yanlong Kong; Haitao Shi; Bitong Xu; Bo Tang; Congbin Li; Yitian Chen; Jing Chen; Juan Du; Yadong Zhang

Materials Today Bio (Dec 2022)

A bionic multichannel nanofiber conduit carrying Tubastatin A for repairing injured spinal cord

Shiyang Liao,
Yonghang Liu,
Yanlong Kong,
Haitao Shi,
Bitong Xu,
Bo Tang,
Congbin Li,
Yitian Chen,
Jing Chen,
Juan Du,
Yadong Zhang

Affiliations

Shiyang Liao: Fengxian Hospital, School of Medicine, Anhui University of Science and Technology, 6600 Nanfeng Hwy, Shanghai, 201499, PR China
Yonghang Liu: School of Chemistry and Chemical Engineering, Shanghai Engineering Research Center of Pharmaceutical Intelligent Equipment, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Non-coding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, 333 Longteng Rd, Shanghai, 201620, PR China
Yanlong Kong: Fengxian Hospital, School of Medicine, Anhui University of Science and Technology, 6600 Nanfeng Hwy, Shanghai, 201499, PR China
Haitao Shi: Department of Spine, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, 510515, PR China
Bitong Xu: Department of Spine, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, 510515, PR China
Bo Tang: Department of Spine, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, 510515, PR China
Congbin Li: Fengxian Hospital, School of Medicine, Anhui University of Science and Technology, 6600 Nanfeng Hwy, Shanghai, 201499, PR China
Yitian Chen: Department of Spine, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, 510515, PR China
Jing Chen: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Rd, Shanghai, 201203, PR China
Juan Du: School of Chemistry and Chemical Engineering, Shanghai Engineering Research Center of Pharmaceutical Intelligent Equipment, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Non-coding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, 333 Longteng Rd, Shanghai, 201620, PR China; Corresponding author. School of Chemistry and Chemical Engineering, Shanghai Engineering Research Center of Pharmaceutical Intelligent Equipment, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Non-coding RNA, Institute for Frontier Medical Technology, Shanghai University of Engineering Science, 333 Longteng Rd, Shanghai, 201620, PR China.
Yadong Zhang: Fengxian Hospital, School of Medicine, Anhui University of Science and Technology, 6600 Nanfeng Hwy, Shanghai, 201499, PR China; Department of Spine, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, 510515, PR China; Corresponding author. Fengxian Hospital, School of Medicine, Anhui University of Science and Technology, 6600 Nanfeng Hwy, Shanghai, 201499, PR China.

Journal volume & issue: Vol. 17
p. 100454

Abstract

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Spinal cord injury is a kind of nerve injury disease with high disability rate. The bioscaffold, which presents a biomimetic structure, can be used as “bridge” to fill the cavity formed by the liquefaction and necrosis of spinal nerve cells, and connects the two ends of the fracture to promote the effective recovery of nerve function. Tubasatin A (TUBA) is a potent selective histone deacetylase 6 (HDAC6) inhibitor, which can inhibit the overexpression of HDAC6 after spinal cord injury. However, TUBA is limited by high efflux ratios, low brain penetration and uptake in the treatment of spinal cord injury. Therefore, an effective carrier with efficient load rate, sustained drug release profile, and prominent repair effect is urgent to be developed. In this study, we have prepared a bionic multichannel Tubasatin A loaded nanofiber conduit (SC-TUBA(+)) through random electrospinning and post-triple network bond crosslinking for inhibiting HDAC6 as well as promoting axonal regeneration during spinal cord injury treatment. The Tubasatin A-loaded nanofibers were shown to be successfully contained in poly(glycolide-co-ε-caprolactone) (PGCL)/silk fibroin (SF) matrix, and the formed PGCL/SF-TUBA nanofibers exhibited an uniform and smooth morphology and appropriate surface wettability. Importantly, the TUBA loaded nanofibers showed a sustained-release profile, and still maintains activity and promoted the extension of axonal. In addition, the total transection large span model of rat back and immunofluorescent labeling, histological, and neurobehavioral analysis were performed for inducing spinal cord injury at T9-10, evaluating therapeutic efficiency of SC-TUBA(+), and elucidating the mechanism of TUBA release system in vivo. All the results demonstrated the significantly reduced glial scar formation, increased nerve fiber number, inhibited inflammation, reduced demyelination and protected bladder tissue of TUBA-loaded nanofibers for spinal cord injury compared to SC-TUBA, SC and Control groups, indicating their great potential for injured spinal cord healing clinically.

Published in Materials Today Bio

ISSN: 2590-0064 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: https://www.journals.elsevier.com/materials-today-bio

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