The goal of this study is to determine the feasibility of using a dense, semipermeable polymer membrane for immuno-isolation of foreign tissue in a hybrid artificial organ. A series of polymers will be synthesized and characterized for permeability, cytotoxicity and biostability. The polymer composition/morphology will be varied to yield a series of polymers with stepwise increasing permeability. Membranes will be cast from solution onto release liner, using a laboratory web coater under uniform conditions of air flow and thermal history. The same casting solution will be used to prepare small-diameter, hollow-fiber membranes for use as cell packets for mouse implant and in vitro cell growth experiments. Using a series of permanent solutions, the permeability of the flat membranes to water, glucose and several proteins will be measured in a non-steady-state diffusion experiment. Sensitive calorimetric/staining methods will be used to quantify glucose and proteins which permeate the membranes for calculation of permeability coefficients for selected permanent/membrane pairs. In Phase II we will build and implant hybrid organs with protective, selectively-permeable barriers for cultured and/or genetically engineered cells. In Phase III the membranes developed in Phase II will be offered commercially by our licensee as (components of) hybrid artificial organs.
