Development of a human cell-based prosthesis for the repair of spinal cord injury in humans

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Pegram, H, 2019. Development of a human cell-based prosthesis for the repair of spinal cord injury in humans. PhD, Nottingham Trent University.

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Abstract

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.

Item Type:	Thesis
Creators:	Pegram, H.
Date:	June 2019
Rights:	The copyright in this work is held by the author. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed to the author.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	02 Oct 2019 13:16
Last Modified:	28 Sep 2021 03:00
URI:	https://irep.ntu.ac.uk/id/eprint/37896