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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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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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.</description><identifier>ISSN: 2046-2069</identifier><identifier>EISSN: 2046-2069</identifier><identifier>DOI: 10.1039/d0ra02661a</identifier><identifier>PMID: 35518337</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Apoptosis ; Biocompatibility ; Central nervous system ; Chemistry ; Elongation ; Glycolic acid ; Homology ; Immunofluorescence ; Implantation ; Microspheres ; Phosphorylation ; Recovery ; Regeneration ; Scaffolds ; Spinal cord injuries ; Stem cells ; Surgical implants</subject><ispartof>RSC advances, 2020-05, Vol.1 (32), p.18677-18686</ispartof><rights>This journal is © The Royal Society of Chemistry.</rights><rights>Copyright Royal Society of Chemistry 2020</rights><rights>This journal is © The Royal Society of Chemistry 2020 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-16cd75dac6efbb1f7a0185f83d6cc027acacd7c8add9621e576951033d81b2aa3</citedby><cites>FETCH-LOGICAL-c495t-16cd75dac6efbb1f7a0185f83d6cc027acacd7c8add9621e576951033d81b2aa3</cites><orcidid>0000-0002-0141-7380</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053942/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053942/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35518337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury</title><title>RSC advances</title><addtitle>RSC Adv</addtitle><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.</description><subject>Apoptosis</subject><subject>Biocompatibility</subject><subject>Central nervous system</subject><subject>Chemistry</subject><subject>Elongation</subject><subject>Glycolic acid</subject><subject>Homology</subject><subject>Immunofluorescence</subject><subject>Implantation</subject><subject>Microspheres</subject><subject>Phosphorylation</subject><subject>Recovery</subject><subject>Regeneration</subject><subject>Scaffolds</subject><subject>Spinal cord injuries</subject><subject>Stem cells</subject><subject>Surgical implants</subject><issn>2046-2069</issn><issn>2046-2069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kk1v1DAQhi1ERau2F-4gIy4t0lI7iZ3kghSVUpBWAiHgak38sfUqsYOdVCz_pP-2TrcsLQd88djz-PV4XiP0nJK3lOT1mSIBSMY5hSfoICMFX2SE108fxPvoOMY1SYMzmnH6DO3njNEqz8sDdNNI3XVTB8H-1grHwTrosPQhxRKM8Z2K2Lq0MfgAo3Ur3A4_TgYrT8--LC8b3FsZfByudNARD8H3ftQYfvlZJuiVdno-5h0Gp7CZnJwXdznpr3XYYDCjDo8utm49hc0R2jPQRX18Px-i7x8uvp1_XCw_X346b5YLWdRsXFAuVckUSK5N21JTAqEVM1WuuJQkK0FCAmQFStU8o5qVvGapc7mqaJsB5Ifo3VZ3mNpeK6ndGKATQ7A9hI3wYMXjjLNXYuWvRU1YXhdZEji5Fwj-56TjKHob566C036KYjaHVLRgNKGv_0HXfgrp4YkqSMF4UWZFot5sqbmzMWizK4YSMZsu3pOvzZ3pTYJfPix_h_6xOAGvtkCIcpf9-2vEoExiXvyPyW8B4LPBXg</recordid><startdate>20200518</startdate><enddate>20200518</enddate><creator>Liu, Jia</creator><creator>Li, Kai</creator><creator>Huang, Ke</creator><creator>Yang, Chengliang</creator><creator>Huang, Zhipeng</creator><creator>Zhao, Xingchang</creator><creator>Song, Shiqiang</creator><creator>Pang, Taisen</creator><creator>Zhou, Jing</creator><creator>Wang, Yuhai</creator><creator>Wang, Chong</creator><creator>Tang, Yujin</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0141-7380</orcidid></search><sort><creationdate>20200518</creationdate><title>Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury</title><author>Liu, Jia ; 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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source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central |
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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