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Title: Development of a human cell-based prosthesis for the repair of spinal cord injury in humans
Author: Pegram, Henry
ISNI:       0000 0004 7971 4873
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2019
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Spinal cord injury (SCI) is a devastating condition that results in a usually permanent disability. Mainstream treatments are limited to stabilisation and debris clearance, followed by early rehabilitation (Chen, Y. et al. 2013). This project investigated bio-functional aligned nanofibre scaffolds as components for personalised prostheses for SCI neural pathway repair, using an in-vitro lesion model of SCI supporting the 3Rs framework. The goal was to design an appropriate nanofibre prosthesis and establish scaffold optimisation parameters for incorporation of neural cell populations. Having a fully characterised prosthesis design, SCI patient's repair could be personalised according to the necessary requirements using lamination of engineered scaffold layers. This investigation built evidence to achieve: 1. Testing of a spectrum of prosthesis designs, engineered to maximise potential neuronal migration and elongation into and within a scaffold. 2. Advances in in-vitro SCI modelling in the form of a fibre-based SCI lesion which may be used as a platform for testing a wide spectrum of treatment materials and conditions. In this investigation, scaffold parameters were optimised to neuronal (SH-SY5Y) and glial (U87-MG) cells representing human neural cell populations. Evidence suggested that PAN best supported neuronal populations and PAN-Jeffamine® best supported glial populations in terms of long-term viability and neuronal axonal length over a period of differentiation. A multi-layered design hosting neural cell populations on discrete layers, suggested that indirect co-culture improved axon length and long-term viability, as much as direct co-culture. To limit inter-layer migration (but maintain the beneficial effects of indirect co-culture), a porous barrier was introduced between these layers. Welded nanofibre showed promise in maintaining long term cell viability and maximising neuronal axon length. To encourage neuronal migration (from the injury sight) into a supportive structure, a collagen gel incorporating cryofractured nanofibre interface showed promise in promoting neuronal migration whilst limiting glial migration. This approach could 'plug' the ends of any developed prosthesis and mediate entry of neurones into the structure. A nanofibre-based model was also developed using the same principles developed in prosthesis development which showed multiple hallmarks of SCI. Evidence obtained allowed development of a potential prosthesis structure, constructed of repeating units of nanofibre suited to neuronal recovery and resident supportive cells, separated by physical barriers. In the future, in place of resident supportive clonal astroglial U87-MG cells, the investigation aims to integrate human Mesenchymal Stem cells (MSC's) and Olfactory Ensheathing Cells (OEC's) as feeder cellularised layers. A diagrammatic summary of the proposed prosthesis is shown in figure 1.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available