(BBSRC DTP) Tissue engineering the oesophagus

This proposal will investigate the development of an in vitro engineered construct for oesophageal tissue engineering. A combination of synthetic, self-assembling peptide hydrogels (from PeptiGelDesign) with fibrous sheets to form a layered scaffold will provide a tissue engineering approach to full thickness repair of oesophageal defects. In previous research we have already shown the hydrogels support the activity and function of primary oesophageal cells, leading to epithelialisation and stratification during in vitro 3D coculture.
In addition we have shown that the gels support the viability of oesophageal stromal fibroblasts. Positive expression of typical epithelial markers (ZO-1 and cytokeratins) was detected using immunocytochemistry at day 3 in culture. This proposal will take our preliminary short term hydrogel data forward to develop a triple layered structure mimicking the architecture of the oesophagus, using novel 3D scaffolding techniques. This will be composed of the mucosa (epithelium), submucosa (fibroblasts & connective tissue) and muscularis layers (smooth muscle cells with layers having a parallel aligned architecture, cirucular or longitudinal in direction). The main focus of the proposal is the optimisation of the scaffold architecture based on cell-material interactions and matrix production/gene expression. The resulting platform technology could be used for various conditions affecting the oesophagus and also translated for use within other similar layered structures within the human body.