An in vitro spinal cord injury model to screen neuroregenerative materials

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.

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. https://doi.org/10.1016/j.biomaterials.2014.01.022

• Journal Article Type: Article
• Acceptance Date: Jan 8, 2014
• Online Publication Date: Jan 29, 2014
• Publication Date: 2014-04
• Deposit Date: Jun 7, 2023
• Journal: Biomaterials
• Print ISSN: 0142-9612
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 35
• Issue: 12
• Pages: 3756-3765
• DOI: https://doi.org/10.1016/j.biomaterials.2014.01.022
• Keywords: Mechanics of Materials; Biomaterials; Biophysics; Ceramics and Composites; Bioengineering; Organotypic slice culture; Spinal cord injury; In vitro model; Electrospinning; Aligned nanofibre; 3R's
• Additional Information: This article is maintained by: Elsevier; Article Title: An in vitro spinal cord injury model to screen neuroregenerative materials; Journal Title: Biomaterials; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.biomaterials.2014.01.022; Content Type: article; Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.