Development of a hybrid artificial pancreas with a dense polyurethane membrane.

We have synthesized a series of strong, elastomeric polyurethaneureas and have used them to fabricate non-porous film and hollow fiber membranes. The solvent cast membranes are non cytotoxic, angiogenic, and permeable to gases, nutrients, secretagogues, and cell products via purely concentration driven transport. Permeability to water, glucose, and protein increases monotonically with membrane water absorption above a threshold value. Water absorption increases with soft segment hydrophilicity, soft segment molecular weight, and soft segment volume fraction of the (dry) segmented polyurethanes. Cell lines (RAJI and MOPC-31C) and primary cells (porcine islets) contained within our membranes have been maintained in culture for up to 6 months with nutrients supplied only by the external media. Cells within membrane devices were protected from immune rejection when implanted into murine hosts. Simple, compact devices containing porcine islets restored normoglycemia and near normal response to glucose tolerance tests in diabetic mice for at least 2 months. Explants had a high degree of vascularization adjacent to the membrane, with little or no fibrous tissue. These properties, and the material's ability to support cell function and protect xenogeneic cells from immunologic rejection, suggest that it would be useful in the construction of hybrid artificial organs and in in vitro cell culture.