An in vitro spinal cord injury model to screen neuroregenerative materials

Hdl Handle:
http://hdl.handle.net/10034/604949
Title:
An in vitro spinal cord injury model to screen neuroregenerative materials
Authors:
Weightman, Alan P.; Pickard, Mark R.; Yang, Ying; Chari, Divya M.
Abstract:
Implantable 'structural bridges' based on nanofabricated polymer scaffolds have great promise to aid spinal cord regeneration. Their development (optimal formulations, surface functionalizations, safety, topographical influences and degradation profiles) is heavily reliant on live animal injury models. These have several disadvantages including invasive surgical procedures, ethical issues, high animal usage, technical complexity and expense. In vitro 3-D organotypic slice arrays could offer a solution to overcome these challenges, but their utility for nanomaterials testing is undetermined. We have developed an in vitro model of spinal cord injury that replicates stereotypical cellular responses to neurological injury in vivo, viz. reactive gliosis, microglial infiltration and limited nerve fibre outgrowth. We describe a facile method to safely incorporate aligned, poly-lactic acid nanofibre meshes (±poly-lysine + laminin coating) within injury sites using a lightweight construct. Patterns of nanotopography induced outgrowth/alignment of astrocytes and neurons in the in vitro model were strikingly similar to that induced by comparable materials in related studies in vivo. This highlights the value of our model in providing biologically-relevant readouts of the regeneration-promoting capacity of synthetic bridges within the complex environment of spinal cord lesions. Our approach can serve as a prototype to develop versatile bio-screening systems to identify materials/combinatorial strategies for regenerative medicine, whilst reducing live animal experimentation.
Affiliation:
Keele University
Citation:
Weightman, A. P., Pickard, M. R., Yang, Y., & Chari, D. M. (2014). An in vitro spinal cord injury model to screen neuroregenerative materials. Biomaterials, 35(12), 3756-3765. DOI: 10.1016/j.biomaterials.2014.01.022
Publisher:
Elsevier
Journal:
Biomaterials
Publication Date:
29-Jan-2014
URI:
http://hdl.handle.net/10034/604949
DOI:
10.1016/j.biomaterials.2014.01.022
Additional Links:
http://www.sciencedirect.com/science/article/pii/S0142961214000246
Type:
Article
Language:
en
EISSN:
1878-5905
Sponsors:
EPSRC Doctoral Training Centre in regenerative medicine (EP/F500491/1)
Appears in Collections:
Institute of Medicine

Full metadata record

DC FieldValue Language
dc.contributor.authorWeightman, Alan P.en
dc.contributor.authorPickard, Mark R.en
dc.contributor.authorYang, Yingen
dc.contributor.authorChari, Divya M.en
dc.date.accessioned2016-04-11T08:40:23Zen
dc.date.available2016-04-11T08:40:23Zen
dc.date.issued2014-01-29en
dc.identifier.citationWeightman, A. P., Pickard, M. R., Yang, Y., & Chari, D. M. (2014). An in vitro spinal cord injury model to screen neuroregenerative materials. Biomaterials, 35(12), 3756-3765. DOI: 10.1016/j.biomaterials.2014.01.022en
dc.identifier.doi10.1016/j.biomaterials.2014.01.022en
dc.identifier.urihttp://hdl.handle.net/10034/604949en
dc.description.abstractImplantable 'structural bridges' based on nanofabricated polymer scaffolds have great promise to aid spinal cord regeneration. Their development (optimal formulations, surface functionalizations, safety, topographical influences and degradation profiles) is heavily reliant on live animal injury models. These have several disadvantages including invasive surgical procedures, ethical issues, high animal usage, technical complexity and expense. In vitro 3-D organotypic slice arrays could offer a solution to overcome these challenges, but their utility for nanomaterials testing is undetermined. We have developed an in vitro model of spinal cord injury that replicates stereotypical cellular responses to neurological injury in vivo, viz. reactive gliosis, microglial infiltration and limited nerve fibre outgrowth. We describe a facile method to safely incorporate aligned, poly-lactic acid nanofibre meshes (±poly-lysine + laminin coating) within injury sites using a lightweight construct. Patterns of nanotopography induced outgrowth/alignment of astrocytes and neurons in the in vitro model were strikingly similar to that induced by comparable materials in related studies in vivo. This highlights the value of our model in providing biologically-relevant readouts of the regeneration-promoting capacity of synthetic bridges within the complex environment of spinal cord lesions. Our approach can serve as a prototype to develop versatile bio-screening systems to identify materials/combinatorial strategies for regenerative medicine, whilst reducing live animal experimentation.en
dc.description.sponsorshipEPSRC Doctoral Training Centre in regenerative medicine (EP/F500491/1)en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0142961214000246en
dc.subject3R'sen
dc.subjectAligned nanofibreen
dc.subjectElectrospinningen
dc.subjectIn vitro modelen
dc.subjectOrganotypic slice cultureen
dc.subjectSpinal cord injuryen
dc.titleAn in vitro spinal cord injury model to screen neuroregenerative materialsen
dc.typeArticleen
dc.identifier.eissn1878-5905en
dc.contributor.departmentKeele Universityen
dc.identifier.journalBiomaterialsen
dc.date.accepted2013-01-08en
or.grant.openaccessYesen
rioxxterms.funderxxen
rioxxterms.identifier.projectxxen
rioxxterms.versionAMen
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