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Article: Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair

TitleSustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
Authors
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/
Citation
Journal Of Biomedical Materials Research - Part A, 2012, v. 100 A n. 1, p. 236-242 How to Cite?
Abstract
Nerve 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.
Persistent Identifierhttp://hdl.handle.net/10722/139433
ISSN
2013 Impact Factor: 2.841
2013 SCImago Journal Rankings: 1.079
ISI Accession Number ID
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

References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Ten_HK
dc.contributor.authorXu, Jen_HK
dc.contributor.authorChan, BPen_HK
dc.contributor.authorChew, SYen_HK
dc.date.accessioned2011-09-23T05:49:26Z-
dc.date.available2011-09-23T05:49:26Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal Of Biomedical Materials Research - Part A, 2012, v. 100 A n. 1, p. 236-242en_HK
dc.identifier.issn1549-3296en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139433-
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.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0021-9304/en_HK
dc.relation.ispartofJournal of Biomedical Materials Research - Part Aen_HK
dc.rightsJournal of Biomedical Materials Research Part A. Copyright © John Wiley & Sons, Inc.-
dc.subjectelectrospinningen_HK
dc.subjectglial scaren_HK
dc.subjectnerve regenerationen_HK
dc.subjectneural tissue engineeringen_HK
dc.subjectneurite outgrowthen_HK
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.titleSustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repairen_HK
dc.typeArticleen_HK
dc.identifier.emailChan, BP:bpchan@hkucc.hku.hken_HK
dc.identifier.authorityChan, BP=rp00087en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/jbm.a.33271en_HK
dc.identifier.pmid22042649en_HK
dc.identifier.scopuseid_2-s2.0-81855201998en_HK
dc.identifier.hkuros196475en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-81855201998&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume100 Aen_HK
dc.identifier.issue1en_HK
dc.identifier.spage236en_HK
dc.identifier.epage242en_HK
dc.identifier.isiWOS:000297740800028-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLiu, T=9736097100en_HK
dc.identifier.scopusauthoridXu, J=54584728500en_HK
dc.identifier.scopusauthoridChan, BP=7201530390en_HK
dc.identifier.scopusauthoridChew, SY=8656381200en_HK

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