Christopher, M.; (2005) Studies to allow the consistent fabrication of many units of engineered tissue. Doctoral thesis , University of London.

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Abstract

Tissue engineering is the regeneration of tissues through the use of cells with the aid of scaffolds. Such in vitro fabrication of tissues is beginning to become an option for the management of patients who have irreversible failure of an organ. There are many technical challenges to overcome before 'off-the-shelf' tissues that represent the translation of scientific discoveries into routine treatments (or millions of patients becomes a reality. To meet this demand, the products must be manufactured reproducibly and in large numbers employing current good tissue practice (cGTP). This thesis takes a whole bioprocess approach and includes: Bioreador design A new and novel methodology is described which potentially allows any tubular organ to be fabricated using an easily scalable liquid based technique suited to automated mass- production. It is novel in that it employs a single multitasking chamber which functions as both a "dynamic former" to create a precise tubular cell/polymer construct and then acts as the core of the bioreactor in which to grow the tissue. Optical coherence tomography (OCT) OCT is an advanced non-invasive high-resolution clinical imaging technique. This thesis describes both its initial application to the engineering of tissue as a means of imaging a construct within its individual bioreactor and also the use of Doppler enhanced OCT to qualitatively and quantitatively image the flow of culture medium through the construct. Polymer scaffold Typically, tissue engineers construct a scaffold and then seed it with cells. This has inherent difficulties including the achievement of homogeneous seeding densities. An alternative is described whereby cells and liquid polymer are mixed prior to scaffold formation. Stem cells Because of the novel approach to construct fabrication, rat smooth muscle cells were used for "range-finding" experiments. Later experiments deployed human adult mesenchymal stem cells (MSCs) which were shown to network within the tubular constructs.

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