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)

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: Barnett, Professor Susan and Lindsay, Dr Susan and Riehle, Dr Mathis and Riddell, Professor John and Hosseinzadeh, Sara
• 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 > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
169822		Development of polymer scaffolds for use in the repair of spinal cord injury	Susan Barnett	Medical Research Scotland (MEDRESSC)	PhD-718-2013	III - Immunology
173658		Heparan mimetics as a novel therapeutic for multiple sclerosis	Susan Barnett	Multiple Sclerosis Society (MS)	56	III - Immunology