A multimodal neuromodulation approach to nervous tissue repair and regeneration
Britton, James
Britton, James
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Identifiers
http://hdl.handle.net/10379/17109
https://doi.org/10.13025/17454
https://doi.org/10.13025/17454
Repository DOI
Publication Date
2022-01-06
Type
Thesis
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Abstract
Regeneration of damaged nervous tissue is one of the remaining frontiers for bioengineers. Nerve tissue injuries have devastating consequences and carry substantial economic and social implications. For example, the annual incidence of spinal cord injury in the United States is approximately 18,000. Injuries caused by trauma from sports injuries or road traffic accidents can lead to varying degrees of paralysis. In recent decades, scientists and engineers have explored a range of therapies to aid in the regeneration of damaged nervous tissue. Cellular therapies, tissue-engineered implantable scaffolds, and electrical stimulation, have all be clinical trials with varying degrees of success. Considering this, there is a general consensus in the field that a combinatory therapeutic approach will be required to yield meaningful therapeutic outcomes for spinal cord injury patients. This project aimed to develop three therapeutic interventions that can be combined to create a medical device which can maximise the potential regeneration of axons after spinal cord injury. In chapter one of this thesis, a general overview of the current approaches used to promote axon regeneration and restore function after injury are discussed. In the first experimental chapter of this thesis, a photocrosslinkable hyaluronic acid bioink was developed that can be used to fabricate aligned nerve guidance hydrogels with applications in spinal cord regeneration (Chapter 2). Following this, biocompatible flexible microelectronics were developed using extrusion-based additive manufacturing with applications in the recording and stimulation within the nervous system (Chapter 3). Additionally, the development of conductive Poly(3,4-ethylenedioxythiophene) hollow nanospheres was explored for applications in neuroelectrode functionalisation (Chapter 4). Following this, A piezoelectric bioreactor system was developed to explore the modulatory effect of direct electromechanical stimulation to cellular function. This in vitro cell culture system has application in the testing and screening of bioelectronic implants before pre-clinical evaluation (Chapter 5). The final chapter of this thesis contains an overall conclusion to this work along with future directions (Chapter 6).
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Publisher
NUI Galway