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Fibrous scaffolds for neural tissue engineering in the auditory system

Ngamkham, K; (2016) Fibrous scaffolds for neural tissue engineering in the auditory system. Doctoral thesis , UCL (University College London).

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Abstract

Hearing loss is a condition highly prevalent worldwide. It affects people of a broad age range since the causes and risk factors are varied. At present, some types of hearing impairments have a palliative treatment whereas some, especially for those where otic neurons are damaged, cannot be properly treated. Recent findings had shown it is possible to use human embryonic stem cell-derived otic neural progenitors (ONPs) as a new mode of treating hearing loss caused by damage to the spiral ganglion neurons (SGNs). To improve the efficiency and overcome some limitations of this treatment, we have applied the principle of tissue engineering, which involves an interaction between cells and extracellular matrix-mimicking construct. Here, we describe the influence of poly(l-lactic acid)(PLLA) aligned fibres and cell-adhesive peptide (RGD and IKVAV) conjugated amphiphilic diblock copolymer (POEGMA-PLA and/or PMPC-PLA) functionalised aligned fibres on ONP cell morphology, proliferation, neuronal differentiation and establishment of neural polarity. The results show that most of ONPs on aligned PLLA and chosen formulations of functionalised fibres exhibited bipolar morphology and extended their neurites along the major fibre axis. Their proliferation was lower than those in 2D culture but the differentiation of ONPs on aligned PLLA and peptide conjugated amphiphilic diblock copolymer fibres were significantly enhanced comparing to 2D even without any neutralising agents as indicated by the fluorescence intensity and number of cells that were positive for neuronal markers (β-tubulin III and NF200). The expression patterns of spiral ganglion molecular markers (MMP13, NPR2 and NTNG1) also demonstrate the differentiation of ONP when cultured on aligned PLLA fibres. Moreover, neural polarity markers (TAU and/or MAP2) were induced after 14 days in culture. The results also revealed that the chosen formulations of RGD and IKVAV conjugated diblock copolymer fibres could drive the differentiation of ONPs better than aligned PLLA fibres and make them a promising scaffolds for the tissue engineering of otic nerves or spiral ganglion neurons.

Type: Thesis (Doctoral)
Title: Fibrous scaffolds for neural tissue engineering in the auditory system
Event: University College London
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/1530940
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