Tissue engineering an artificial salivary gland device

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Why should anyone wish to construct an artificial salivary gland (SG)? The answer lies in filling a clinical need for the 4,000 Canadians diagnosed each year with cancer of the head and neck. Worldwide, this amounts to 640,000 new patients yearly. These patients receive therapeutic irradiation as a treatment for their cancer. SGs in the field of radiation are severely damaged, resulting in a loss of salivary acinar cells, the principal site of fluid secretion (i.e. saliva). These patients experience considerable morbidity and discomfort such as dry mouth, difficulty swallowing, tooth decay, loss of taste to foods, and oro-pharyngeal infections/ ulcers. For many patients, there is currently no available adequate treatment. They cannot utilize existing pharmacological tools (such as saliva-stimulating drugs), which require the presence of some surviving epithelial tissue. Accordingly, we have been motivated to develop an orally implantable fluid secretory device for treating such patients. To date, a major hurdle in the fabrication of our device has been finding a suitable graft cells that can secrete water (saliva) and can be expanded readily for incorporation in the device. Our objectives for this proposal are to: 1) Build a three-dimensional (3-D) artificial SG prototype and test if it can move fluid unidirectionally; 2) Engineer human saliva-secreting cells and assess their capability to tissue assembly in 3-D gel environments (such as fibronectin gel, basement membrane extract gel, chondroitin sulfate and polyethylene glycol hydrogel); 3) Assess two methods to deliver engineered human saliva-secreting cells into mice with SGs damaged by irradiation: a) by direct injection into the glandular tissue, or b) by intra-ductal cannulation and infusing the cells under pressure. The impact of re-engineering epithelial cells to possess a fluid secretory function in the artificial SG device or in 3-D gels would be a key breakthrough for the many patients affected with dry mouth. It could offer to millions of patients worldwide, having reduced or no saliva output, effective treatment option. These include the potential for regeneration and repair of salivary acinar cells in adult glands, and the potential for these cells to be used in an implantable artificial SG device.