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Spiral Ganglion Neurite Outgrowth and Pathfinding on Electrospun Microfibrous Piezoelectric Nanocomposite Polymer Scaffolds

Zabalawi, Hassan A.; (2018) Spiral Ganglion Neurite Outgrowth and Pathfinding on Electrospun Microfibrous Piezoelectric Nanocomposite Polymer Scaffolds. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Sensorineural hearing loss (SNHL) can be caused by hair cell loss and spiral ganglion neurone (SGN) degeneration. Cochlear implants (CIs), the only means of restoring residual hearing to profoundly deaf people, stimulate possible preserved SGNs electrically. Thus, SGN degeneration dictates the efficacy of CIs. SGN degeneration reduces sensitivity and frequency selectivity. In addition, stimulation thresholds increase due to SGN degeneration consequently increasing power demands. The replacement of auditory neurones with proper functional spatial alignment is an important step in the attempt to restore auditory function. This study adopts a tissue-engineering approach. We examined the viability of polyvinylidene fluoride (PVDF) and polyvinylidene trifluoroethylene (P(VDF-TrFE)). P(VDF-TrFE) was chosen to add directional growth cues through electrospinning aligned microfibrous scaffolds. The effects of the scaffolds on the length and orientation of re-growing SGN neurites and glia were tested in vitro using primary murine cultures. Two methods of SGN preparation were compared; explants and dissociated cultures. Primary SGNs showed preferential affinity to P(VDF-TrFE) microfibres and the microfibrous scaffolds were found to promote aligned SGN neurite regrowth compared to glass coverslips. Subsequently, we doped the electrospun P(VDF-TrFE) microfibres with carbon nanotubes (CNT) to optimise the scaffold mechanically and electrically. The CNT addition was found to be biocompatible and promoted aligned SGN neurite regrowth. The CNT doping enhanced the mechanical properties of the microfibres and improved scaffold handling. Moreover, the scaffolds could be biofunctionalized with neurone modulating drugs. Preliminary testing of gamma-secretase inhibitor (LY411575) showed promising regenerative effects on SGNs in vitro. In conclusion, electrospun aligned microfibrous P(VDF-TrFE)-CNT nanocomposite scaffolds can modulate glial and SGN neurite and axon organization in vitro. Combined with a specific protocol of electrical induction in the first weeks of implantation, the piezoelectric fibrous scaffold could significantly improve cochlear implantation results, frequency selectivity and minimize power demands.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Spiral Ganglion Neurite Outgrowth and Pathfinding on Electrospun Microfibrous Piezoelectric Nanocomposite Polymer Scaffolds
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2018. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10061643
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