Robert S. Ward

Noninvasive quantification of platelet accumulation and release on indwelling venous catheters.

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 materials 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.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 materials 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.

Proliferation and Interactions of Several Cell Types Encapsulated Within Dense (Non-Porous) Protein-Permeable Polyurethane Membranes

Protein-permeable dense (non-porous) urethane membranes have been evaluated for in vitro cell culture, and in vivo cell encapsulation. Polyurethane membranes were designed to exhibit permeability to proteins, gases, and nutrients without the existence of pores. The membranes are non-cytotoxic, angiogenic, and permeable to gases, nutrients, secretagogues and cell products via purely concentration-driven transport. Non-anchorage and anchorage dependent cells were grown encapsulated within the membrane and with the membrane as a growth substrate. Several non-anchorage dependent cell types proliferated within the membrane both in-vitro and in-vivo . Anchorage-dependent cells were grown on the membranes as a substrate. Encapsulated cells have been maintained in culture for up to six months with nutrients supplied only by the external media. Immuno-isolation has been demonstrated with cells implanted into murine hosts. Explants of membrane encapsulated cells exhibited a high degree of vascularization, with little or no fibrous tissue. The ability to support cell growth and function, and the ability to protect xenogenic cells from immunologic rejection suggest that the membranes would be useful in the construction of hybrid artificial organs, devices for cell transplantation, and substrates for cell and tissue culture.