A novel poly-ε-lysine based implant, Proliferate®, for promotion of CNS repair following spinal cord injury

Hosseinzadeh, S., Lindsay, S. L., Gallagher, A. G., Wellings, D. A., Riehle, M. O. , Riddell, J. S. and Barnett, S. C. (2020) A novel poly-ε-lysine based implant, Proliferate®, for promotion of CNS repair following spinal cord injury. Biomaterials Science, 8(13), pp. 3611-3627. (doi: 10.1039/D0BM00097C) (PMID:32515439)

[img] Text
220162.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial.

11MB

Abstract

The limited regenerative capacity of the CNS poses formidable challenges to the repair of spinal cord injury (SCI). Two key barriers to repair are (i) the physical gap left by the injury, and (ii) the inhibitory milieu surrounding the injury, the glial scar. Biomaterial implantation into the injury site can fill the cavity, provide a substrate for cell migration, and potentially attenuate the glial scar. We investigated the biological viability of a biocompatible and biodegradable poly-ε-lysine based biomaterial, Proliferate®, in low and high cross-linked forms and when coated with IKVAV peptide, for SCI implantation. We demonstrate altered astrocyte morphology and nestin expression on Proliferate® compared to conventional glass cell coverslips suggesting a less reactive phenotype. Moreover Proliferate® supported myelination in vitro, with myelination observed sooner on IKVAV-coated constructs compared with uncoated Proliferate®, and delayed overall compared with maintenance on glass coverslips. For in vivo implantation, parallel-aligned channels were fabricated into Proliferate® to provide cell guidance cues. Extensive vascularisation and cellular infiltration were observed in constructs implanted in vivo, along with an astrocyte border and microglial response. Axonal ingrowth was observed at the construct border and inside implants in intact channels. We conclude that Proliferate® is a promising biomaterial for implantation following SCI.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hosseinzadeh, Sara and Riehle, Dr Mathis and Barnett, Professor Susan and Lindsay, Dr Susan and Riddell, Professor John
Authors: Hosseinzadeh, S., Lindsay, S. L., Gallagher, A. G., Wellings, D. A., Riehle, M. O., Riddell, J. S., and Barnett, S. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Biomaterials Science
Publisher:Royal Society of Chemistry
ISSN:2047-4830
ISSN (Online):2047-4849
Published Online:03 June 2020
Copyright Holders:Copyright © 2020 The Royal Society of Chemistry
First Published:First published in Biomaterials Science 8(13): 3611-3627
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
169822Development of polymer scaffolds for use in the repair of spinal cord injurySusan BarnettMedical Research Scotland (MEDRESSC)PhD-718-2013III - Immunology
173658Heparan mimetics as a novel therapeutic for multiple sclerosisSusan BarnettMultiple Sclerosis Society (MS)56III - Immunology