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Title: Spiral ganglion neurite outgrowth and pathfinding on electrospun microfibrous piezoelectric nanocomposite polymer scaffolds
Author: Zabalawi, Hassan A.
ISNI:       0000 0004 7661 2126
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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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.
Supervisor: Gale, J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available