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

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 ne...

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Main Authors: Chan, Barbara P., Liu, Ting, Xu, Jinye, Chew, Sing Yian
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2013
Online Access:https://hdl.handle.net/10356/99309
http://hdl.handle.net/10220/17241
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-993092020-03-07T11:35:31Z Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair Chan, Barbara P. Liu, Ting Xu, Jinye Chew, Sing Yian School of Chemical and Biomedical Engineering 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. 2013-11-05T04:20:01Z 2019-12-06T20:05:38Z 2013-11-05T04:20:01Z 2019-12-06T20:05:38Z 2011 2011 Journal Article Liu, T., Xu, J., Chan, B. P., & Chew, S. Y. (2012). Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair. Journal of Biomedical Materials Research Part A, 100A(1), 236-242. 1549-3296 https://hdl.handle.net/10356/99309 http://hdl.handle.net/10220/17241 10.1002/jbm.a.33271 en Journal of biomedical materials research part A
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
description 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.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Chan, Barbara P.
Liu, Ting
Xu, Jinye
Chew, Sing Yian
format Article
author Chan, Barbara P.
Liu, Ting
Xu, Jinye
Chew, Sing Yian
spellingShingle Chan, Barbara P.
Liu, Ting
Xu, Jinye
Chew, Sing Yian
Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
author_sort Chan, Barbara P.
title Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
title_short Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
title_full Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
title_fullStr Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
title_full_unstemmed Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair
title_sort sustained release of neurotrophin-3 and chondroitinase abc from electrospun collagen nanofiber scaffold for spinal cord injury repair
publishDate 2013
url https://hdl.handle.net/10356/99309
http://hdl.handle.net/10220/17241
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