Article: Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
| Title | Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair |
|---|---|
| Authors | Liu, T2 Xu, J1 Chan, BP1 Chew, SY2 |
| Keywords | electrospinning glial scar nerve regeneration neural tissue engineering neurite outgrowth |
| Issue Date | 2012 |
| Publisher | John 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?] DOI: http://dx.doi.org/10.1002/jbm.a.33271 |
| 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. |
| ISSN | 1549-3296 2011 Impact Factor: 2.625 2011 SCImago Journal Rankings: 0.198 |
| DOI | http://dx.doi.org/10.1002/jbm.a.33271 |
| References | References in Scopus |
| dc.contributor.author | Liu, T | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Xu, J | ||||||
| dc.contributor.author | Chan, BP | ||||||
| dc.contributor.author | Chew, SY | ||||||
| dc.date.accessioned | 2011-09-23T05:49:26Z | ||||||
| dc.date.available | 2011-09-23T05:49:26Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.description.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. | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Journal 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.doi | http://dx.doi.org/10.1002/jbm.a.33271 | ||||||
| dc.identifier.epage | 242 | ||||||
| dc.identifier.hkuros | 196475 | ||||||
| dc.identifier.isi | WOS:000297740800028
Funding Information: Contract grant sponsor: National Medical Research Council (NMRC) Exploratory Development Grant, Singapore; contract grant number: NMRC/EDG/0027/2008 | ||||||
| dc.identifier.issn | 1549-3296 2011 Impact Factor: 2.625 2011 SCImago Journal Rankings: 0.198 | ||||||
| dc.identifier.issue | 1 | ||||||
| dc.identifier.pmid | 22042649 | ||||||
| dc.identifier.scopus | eid_2-s2.0-81855201998 | ||||||
| dc.identifier.spage | 236 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/139433 | ||||||
| dc.identifier.volume | 100 A | ||||||
| dc.language | eng | ||||||
| dc.publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0021-9304/ | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Journal of Biomedical Materials Research - Part A | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Journal of Biomedical Materials Research Part A. Copyright © John Wiley & Sons, Inc. | ||||||
| dc.subject.mesh | Chondroitin ABC Lyase - therapeutic use | ||||||
| dc.subject.mesh | Collagen - pharmacology | ||||||
| dc.subject.mesh | Nanofibers - chemistry | ||||||
| dc.subject.mesh | Spinal Cord Injuries - drug therapy - pathology | ||||||
| dc.subject.mesh | Tissue Engineering - methods | ||||||
| dc.subject | electrospinning | ||||||
| dc.subject | glial scar | ||||||
| dc.subject | nerve regeneration | ||||||
| dc.subject | neural tissue engineering | ||||||
| dc.subject | neurite outgrowth | ||||||
| dc.title | Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Nanyang Technological University