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Article: Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
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TitleSustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
 
AuthorsLiu, T2
Xu, J1
Chan, BP1
Chew, SY2
 
Keywordselectrospinning
glial scar
nerve regeneration
neural tissue engineering
neurite outgrowth
 
Issue Date2012
 
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0021-9304/
 
CitationJournal Of Biomedical Materials Research - Part A, 2012, v. 100 A n. 1, p. 236-242 [How to Cite?]
DOI: http://dx.doi.org/10.1002/jbm.a.33271
 
AbstractNerve regeneration after spinal cord injuries (SCI) remains suboptimal despite recent advances in the field. One major hurdle is the rapid clearance of drugs from the injury site, which greatly limits therapeutic outcomes. Nanofiber scaffolds represent a potential class of materials for enhancing nerve regeneration because of its biomimicking architecture. In this study, we investigated the feasibility of incorporating neurotrophin-3 (NT-3) and chondroitinase ABC (ChABC) onto electrospun collagen nanofibers for SCI treatment. By using microbial transglutaminase (mTG) mediated crosslinking, proteins were loaded onto electrospun collagen nanofibers at an efficiency of ∼45-48%. By combining NT-3 with heparin during the protein incorporation process, a sustained release of NT-3 was obtained (∼96% by day 28). As indicated by dorsal root ganglion outgrowth assay, NT-3 incorporated collagen scaffolds supported neuronal culture and neurite outgrowth for a longer time period than bolus delivery of NT-3. The presence of heparin also protected ChABC from degradation. Specifically, as evaluated by dimethylmethylene blue assay, bioactive ChABC was detected from collagen scaffolds for at least 32 days in vitro in the presence of heparin (∼32% of bioactivity retained). In contrast, ChABC bioactivity was only ∼1.9% by day 22 in the absence of heparin. Taken together, these results clearly demonstrated the feasibility of incorporating NT-3 and ChABC via mTG immobilization to produce protein-incorporated collagen nanofibers. Such biofunctional nanofiber constructs may find useful applications in SCI treatment by providing topographical signals and multiple biochemical cues that can promote nerve regeneration while antagonizing axonal growth inhibition for CNS regeneration. Copyright © 2011 Wiley Periodicals, Inc.
 
ISSN1549-3296
2013 Impact Factor: 2.841
2013 SCImago Journal Rankings: 1.079
 
DOIhttp://dx.doi.org/10.1002/jbm.a.33271
 
ISI Accession Number IDWOS:000297740800028
Funding AgencyGrant Number
National Medical Research Council (NMRC), SingaporeNMRC/EDG/0027/2008
MOE AcRF Tier 1, SingaporeRG75/10
Funding Information:

Contract grant sponsor: National Medical Research Council (NMRC) Exploratory Development Grant, Singapore; contract grant number: NMRC/EDG/0027/2008

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLiu, T
 
dc.contributor.authorXu, J
 
dc.contributor.authorChan, BP
 
dc.contributor.authorChew, SY
 
dc.date.accessioned2011-09-23T05:49:26Z
 
dc.date.available2011-09-23T05:49:26Z
 
dc.date.issued2012
 
dc.description.abstractNerve regeneration after spinal cord injuries (SCI) remains suboptimal despite recent advances in the field. One major hurdle is the rapid clearance of drugs from the injury site, which greatly limits therapeutic outcomes. Nanofiber scaffolds represent a potential class of materials for enhancing nerve regeneration because of its biomimicking architecture. In this study, we investigated the feasibility of incorporating neurotrophin-3 (NT-3) and chondroitinase ABC (ChABC) onto electrospun collagen nanofibers for SCI treatment. By using microbial transglutaminase (mTG) mediated crosslinking, proteins were loaded onto electrospun collagen nanofibers at an efficiency of ∼45-48%. By combining NT-3 with heparin during the protein incorporation process, a sustained release of NT-3 was obtained (∼96% by day 28). As indicated by dorsal root ganglion outgrowth assay, NT-3 incorporated collagen scaffolds supported neuronal culture and neurite outgrowth for a longer time period than bolus delivery of NT-3. The presence of heparin also protected ChABC from degradation. Specifically, as evaluated by dimethylmethylene blue assay, bioactive ChABC was detected from collagen scaffolds for at least 32 days in vitro in the presence of heparin (∼32% of bioactivity retained). In contrast, ChABC bioactivity was only ∼1.9% by day 22 in the absence of heparin. Taken together, these results clearly demonstrated the feasibility of incorporating NT-3 and ChABC via mTG immobilization to produce protein-incorporated collagen nanofibers. Such biofunctional nanofiber constructs may find useful applications in SCI treatment by providing topographical signals and multiple biochemical cues that can promote nerve regeneration while antagonizing axonal growth inhibition for CNS regeneration. Copyright © 2011 Wiley Periodicals, Inc.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Biomedical Materials Research - Part A, 2012, v. 100 A n. 1, p. 236-242 [How to Cite?]
DOI: http://dx.doi.org/10.1002/jbm.a.33271
 
dc.identifier.doihttp://dx.doi.org/10.1002/jbm.a.33271
 
dc.identifier.epage242
 
dc.identifier.hkuros196475
 
dc.identifier.isiWOS:000297740800028
Funding AgencyGrant Number
National Medical Research Council (NMRC), SingaporeNMRC/EDG/0027/2008
MOE AcRF Tier 1, SingaporeRG75/10
Funding Information:

Contract grant sponsor: National Medical Research Council (NMRC) Exploratory Development Grant, Singapore; contract grant number: NMRC/EDG/0027/2008

 
dc.identifier.issn1549-3296
2013 Impact Factor: 2.841
2013 SCImago Journal Rankings: 1.079
 
dc.identifier.issue1
 
dc.identifier.pmid22042649
 
dc.identifier.scopuseid_2-s2.0-81855201998
 
dc.identifier.spage236
 
dc.identifier.urihttp://hdl.handle.net/10722/139433
 
dc.identifier.volume100 A
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0021-9304/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Biomedical Materials Research - Part A
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Biomedical Materials Research Part A. Copyright © John Wiley & Sons, Inc.
 
dc.subject.meshChondroitin ABC Lyase - therapeutic use
 
dc.subject.meshCollagen - pharmacology
 
dc.subject.meshNanofibers - chemistry
 
dc.subject.meshSpinal Cord Injuries - drug therapy - pathology
 
dc.subject.meshTissue Engineering - methods
 
dc.subjectelectrospinning
 
dc.subjectglial scar
 
dc.subjectnerve regeneration
 
dc.subjectneural tissue engineering
 
dc.subjectneurite outgrowth
 
dc.titleSustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Nanyang Technological University