An in vitro spinal cord injury model to screen neuroregenerative materials.
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.
Cellular and Neural Engineering Group, Institute for Science and Technology in Medicine, Huxley Building, Keele University, Keele, Staffordshire ST5 5BG, UK; Guy Hilton Research Centre, Institute for Science and Technology in Medicine, Thornburrow Drive, Keele University, Staffordshire ST4 7QB, UK.
Alan P
AP
Weightman
Cellular and Neural Engineering Group, Institute for Science and Technology in Medicine, Huxley Building, Keele University, Keele, Staffordshire ST5 5BG, UK.
Mark R
MR
Pickard
Guy Hilton Research Centre, Institute for Science and Technology in Medicine, Thornburrow Drive, Keele University, Staffordshire ST4 7QB, UK.
Ying
Y
Yang
Cellular and Neural Engineering Group, Institute for Science and Technology in Medicine, Huxley Building, Keele University, Keele, Staffordshire ST5 5BG, UK. Electronic address: d.chari@keele.ac.uk.
Divya M
DM
Chari
D000818:Animals; D001672:Biocompatible Materials; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D051379:Mice; D009416:Nerve Regeneration; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D054457:Tissue Scaffolds
D001672:Biocompatible Materials
3R's; Aligned nanofibre; Electrospinning; In vitro model; Organotypic slice culture; Spinal cord injury