Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury

Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery. Phosphatase and tensin homolog (PTEN) inhibition by pharmacological blockade with bisperoxovanadium (pic) (bpV(pic)) has been reported to increase...

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Veröffentlicht in:RSC advances 2020-05, Vol.1 (32), p.18677-18686
Hauptverfasser: Liu, Jia, Li, Kai, Huang, Ke, Yang, Chengliang, Huang, Zhipeng, Zhao, Xingchang, Song, Shiqiang, Pang, Taisen, Zhou, Jing, Wang, Yuhai, Wang, Chong, Tang, Yujin
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container_issue 32
container_start_page 18677
container_title RSC advances
container_volume 1
creator Liu, Jia
Li, Kai
Huang, Ke
Yang, Chengliang
Huang, Zhipeng
Zhao, Xingchang
Song, Shiqiang
Pang, Taisen
Zhou, Jing
Wang, Yuhai
Wang, Chong
Tang, Yujin
description Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery. Phosphatase and tensin homolog (PTEN) inhibition by pharmacological blockade with bisperoxovanadium (pic) (bpV(pic)) has been reported to increase AKT/mTOR activity and induce robust axonal elongation and regeneration. However, the therapeutic effect of bpV(pic) in treating SCI is limited due to the lack of efficient delivery approaches. In this study, a composite scaffold consisting of an acellular spinal cord (ASC) scaffold and incorporated bpV(pic) loaded poly (lactic- co -glycolic acid) (PLGA) microspheres was developed, in order to improve the therapeutic effect of bpV(pic) on SCI. The inhibition of PTEN activity and activation of the mTORC1/AKT pathway, the axonal regeneration and the markers of apoptosis were analyzed via western blot and immunofluorescence in vitro . The bpV(pic)/PLGA/ASC scaffolds showed excellent biocompatibility and promoted the viability of neural stem cells and axonal growth in vitro . Implantation of the composite scaffold into rats with hemi-sectioned SCI resulted in increased axonal regeneration and functional recovery in vivo . Besides, bpV(pic) inhibited the phosphorylation of PTEN and activated the PI3K/mTOR signaling pathway. The successful construction of the composite scaffold improves the therapeutic effect of bpV(pic) on SCI. Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery.
doi_str_mv 10.1039/d0ra02661a
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Phosphatase and tensin homolog (PTEN) inhibition by pharmacological blockade with bisperoxovanadium (pic) (bpV(pic)) has been reported to increase AKT/mTOR activity and induce robust axonal elongation and regeneration. However, the therapeutic effect of bpV(pic) in treating SCI is limited due to the lack of efficient delivery approaches. In this study, a composite scaffold consisting of an acellular spinal cord (ASC) scaffold and incorporated bpV(pic) loaded poly (lactic- co -glycolic acid) (PLGA) microspheres was developed, in order to improve the therapeutic effect of bpV(pic) on SCI. The inhibition of PTEN activity and activation of the mTORC1/AKT pathway, the axonal regeneration and the markers of apoptosis were analyzed via western blot and immunofluorescence in vitro . The bpV(pic)/PLGA/ASC scaffolds showed excellent biocompatibility and promoted the viability of neural stem cells and axonal growth in vitro . Implantation of the composite scaffold into rats with hemi-sectioned SCI resulted in increased axonal regeneration and functional recovery in vivo . Besides, bpV(pic) inhibited the phosphorylation of PTEN and activated the PI3K/mTOR signaling pathway. The successful construction of the composite scaffold improves the therapeutic effect of bpV(pic) on SCI. 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Phosphatase and tensin homolog (PTEN) inhibition by pharmacological blockade with bisperoxovanadium (pic) (bpV(pic)) has been reported to increase AKT/mTOR activity and induce robust axonal elongation and regeneration. However, the therapeutic effect of bpV(pic) in treating SCI is limited due to the lack of efficient delivery approaches. In this study, a composite scaffold consisting of an acellular spinal cord (ASC) scaffold and incorporated bpV(pic) loaded poly (lactic- co -glycolic acid) (PLGA) microspheres was developed, in order to improve the therapeutic effect of bpV(pic) on SCI. The inhibition of PTEN activity and activation of the mTORC1/AKT pathway, the axonal regeneration and the markers of apoptosis were analyzed via western blot and immunofluorescence in vitro . The bpV(pic)/PLGA/ASC scaffolds showed excellent biocompatibility and promoted the viability of neural stem cells and axonal growth in vitro . Implantation of the composite scaffold into rats with hemi-sectioned SCI resulted in increased axonal regeneration and functional recovery in vivo . Besides, bpV(pic) inhibited the phosphorylation of PTEN and activated the PI3K/mTOR signaling pathway. The successful construction of the composite scaffold improves the therapeutic effect of bpV(pic) on SCI. 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Li, Kai ; Huang, Ke ; Yang, Chengliang ; Huang, Zhipeng ; Zhao, Xingchang ; Song, Shiqiang ; Pang, Taisen ; Zhou, Jing ; Wang, Yuhai ; Wang, Chong ; Tang, Yujin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-16cd75dac6efbb1f7a0185f83d6cc027acacd7c8add9621e576951033d81b2aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Apoptosis</topic><topic>Biocompatibility</topic><topic>Central nervous system</topic><topic>Chemistry</topic><topic>Elongation</topic><topic>Glycolic acid</topic><topic>Homology</topic><topic>Immunofluorescence</topic><topic>Implantation</topic><topic>Microspheres</topic><topic>Phosphorylation</topic><topic>Recovery</topic><topic>Regeneration</topic><topic>Scaffolds</topic><topic>Spinal cord injuries</topic><topic>Stem cells</topic><topic>Surgical implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Jia</creatorcontrib><creatorcontrib>Li, Kai</creatorcontrib><creatorcontrib>Huang, Ke</creatorcontrib><creatorcontrib>Yang, Chengliang</creatorcontrib><creatorcontrib>Huang, Zhipeng</creatorcontrib><creatorcontrib>Zhao, Xingchang</creatorcontrib><creatorcontrib>Song, Shiqiang</creatorcontrib><creatorcontrib>Pang, Taisen</creatorcontrib><creatorcontrib>Zhou, Jing</creatorcontrib><creatorcontrib>Wang, Yuhai</creatorcontrib><creatorcontrib>Wang, Chong</creatorcontrib><creatorcontrib>Tang, Yujin</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RSC advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Jia</au><au>Li, Kai</au><au>Huang, Ke</au><au>Yang, Chengliang</au><au>Huang, Zhipeng</au><au>Zhao, Xingchang</au><au>Song, Shiqiang</au><au>Pang, Taisen</au><au>Zhou, Jing</au><au>Wang, Yuhai</au><au>Wang, Chong</au><au>Tang, Yujin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury</atitle><jtitle>RSC advances</jtitle><addtitle>RSC Adv</addtitle><date>2020-05-18</date><risdate>2020</risdate><volume>1</volume><issue>32</issue><spage>18677</spage><epage>18686</epage><pages>18677-18686</pages><issn>2046-2069</issn><eissn>2046-2069</eissn><abstract>Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery. Phosphatase and tensin homolog (PTEN) inhibition by pharmacological blockade with bisperoxovanadium (pic) (bpV(pic)) has been reported to increase AKT/mTOR activity and induce robust axonal elongation and regeneration. However, the therapeutic effect of bpV(pic) in treating SCI is limited due to the lack of efficient delivery approaches. In this study, a composite scaffold consisting of an acellular spinal cord (ASC) scaffold and incorporated bpV(pic) loaded poly (lactic- co -glycolic acid) (PLGA) microspheres was developed, in order to improve the therapeutic effect of bpV(pic) on SCI. The inhibition of PTEN activity and activation of the mTORC1/AKT pathway, the axonal regeneration and the markers of apoptosis were analyzed via western blot and immunofluorescence in vitro . The bpV(pic)/PLGA/ASC scaffolds showed excellent biocompatibility and promoted the viability of neural stem cells and axonal growth in vitro . Implantation of the composite scaffold into rats with hemi-sectioned SCI resulted in increased axonal regeneration and functional recovery in vivo . Besides, bpV(pic) inhibited the phosphorylation of PTEN and activated the PI3K/mTOR signaling pathway. The successful construction of the composite scaffold improves the therapeutic effect of bpV(pic) on SCI. Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>35518337</pmid><doi>10.1039/d0ra02661a</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0141-7380</orcidid><oa>free_for_read</oa></addata></record>
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subjects Apoptosis
Biocompatibility
Central nervous system
Chemistry
Elongation
Glycolic acid
Homology
Immunofluorescence
Implantation
Microspheres
Phosphorylation
Recovery
Regeneration
Scaffolds
Spinal cord injuries
Stem cells
Surgical implants
title Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury
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