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Design and development of an artificial tracheal replacement with clinical application

Crowley, C; (2016) Design and development of an artificial tracheal replacement with clinical application. Doctoral thesis , UCL (University College London).

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Abstract

People suffering from long-segmental tracheal stenosis and malacia currently have few options clinically available to them. An attractive solution would be to remove the damaged area of the trachea and replace it will a tracheal replacement. However, despite many years of research worldwide, a gold standard replacement is yet to become clinically available. An ideal replacement must avoid luminal collapse yet be flexible. It must be porous, yet also airtight. It must facilitate growth of an airway epithelium and be biocompatible to avoid implant rejection and not require immunosuppressive therapy. This PhD describes the design and development of a synthetic tracheal replacement that aims to satisfy most of these requirements. The tracheal replacement described is manufactured using a nanocomposite material: POSS-PCU. The polymer itself is characterised to assess its suitability and to determine the appropriate fabrication methods for this application. Using two chosen fabrications, the construct is designed to mimic the native airway and characterised with comparisons to native human tissue. The thesis includes a chapter on modifying the surface of the POSS-PCU material via porogen application. The technique substantially increased surface porosity and in vivo studies showed enhanced graft integration. Additionally, a novel application for bioluminescence imaging in tissue engineering is described. With this technique cells can be non-invasively tracked in real-time from tissue culture plates; to the inner lumen of a tubular scaffold in a closed bioreactor system, with potential for in vivo cell tracking. The characterisation and ‘proof-ofconcept’ in vivo study performed, highlight this technique as a valuable tool for cell tracking in tissue engineering applications. In June 2011, the POSS-PCU airway described in this thesis was implanted clinically as a compassionate case. Here, graft manufacture is described as well as a retrospective look at the case with insight into what we might learn from this experience.

Type: Thesis (Doctoral)
Title: Design and development of an artificial tracheal replacement with clinical application
Event: University College London
Language: English
Keywords: Trachea, Tissue Engineering, Regenerative Medicine, Nanotechnology, POSS-PCU, Nanocomposite Polymer
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 Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Development Bio and Cancer Prog
URI: http://discovery.ucl.ac.uk/id/eprint/1485755
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