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

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 e...

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Autores principales: Liao, Shiyang, Liu, Yonghang, Kong, Yanlong, Shi, Haitao, Xu, Bitong, Tang, Bo, Li, Congbin, Chen, Yitian, Chen, Jing, Du, Juan, Zhang, Yadong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9615035/
https://www.ncbi.nlm.nih.gov/pubmed/36310542
http://dx.doi.org/10.1016/j.mtbio.2022.100454
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author Liao, Shiyang
Liu, Yonghang
Kong, Yanlong
Shi, Haitao
Xu, Bitong
Tang, Bo
Li, Congbin
Chen, Yitian
Chen, Jing
Du, Juan
Zhang, Yadong
author_facet Liao, Shiyang
Liu, Yonghang
Kong, Yanlong
Shi, Haitao
Xu, Bitong
Tang, Bo
Li, Congbin
Chen, Yitian
Chen, Jing
Du, Juan
Zhang, Yadong
author_sort Liao, Shiyang
collection PubMed
description 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.
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spelling pubmed-96150352022-10-29 A bionic multichannel nanofiber conduit carrying Tubastatin A for repairing injured spinal cord Liao, Shiyang Liu, Yonghang Kong, Yanlong Shi, Haitao Xu, Bitong Tang, Bo Li, Congbin Chen, Yitian Chen, Jing Du, Juan Zhang, Yadong Mater Today Bio Full Length Article 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. Elsevier 2022-10-15 /pmc/articles/PMC9615035/ /pubmed/36310542 http://dx.doi.org/10.1016/j.mtbio.2022.100454 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Liao, Shiyang
Liu, Yonghang
Kong, Yanlong
Shi, Haitao
Xu, Bitong
Tang, Bo
Li, Congbin
Chen, Yitian
Chen, Jing
Du, Juan
Zhang, Yadong
A bionic multichannel nanofiber conduit carrying Tubastatin A for repairing injured spinal cord
title A bionic multichannel nanofiber conduit carrying Tubastatin A for repairing injured spinal cord
title_full A bionic multichannel nanofiber conduit carrying Tubastatin A for repairing injured spinal cord
title_fullStr A bionic multichannel nanofiber conduit carrying Tubastatin A for repairing injured spinal cord
title_full_unstemmed A bionic multichannel nanofiber conduit carrying Tubastatin A for repairing injured spinal cord
title_short A bionic multichannel nanofiber conduit carrying Tubastatin A for repairing injured spinal cord
title_sort bionic multichannel nanofiber conduit carrying tubastatin a for repairing injured spinal cord
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9615035/
https://www.ncbi.nlm.nih.gov/pubmed/36310542
http://dx.doi.org/10.1016/j.mtbio.2022.100454
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