9320570 Ramirez The research proposed in this application is the study of an intravascular hybrid artificial pancreas (HAP). The HAP consists of a cylindrical inert housing enclosing a single, tubular hollow fiber membrane in a shell-and-tube mass exchanger configuration. Islets can be inoculated into the annular space through a port in the housing. HAPs have been shown by other groups to reverse experimental diabetes in animals, but have not undergone clinical trials to date. Thus, scale-up criteria based on engineering principles are currently lacking. The goal of this project is to attain a more fundamental understanding of the factors which determine the efficiency and durability of insulin release from islets seeded in a HAP device. Specific aims are to: (1) quantify the flow and solute resistance in vitro provided by both the membrane and the seeded islets, (2) quantify the effect of membrane protein "fouling" in vitro on the dynamics of solute transport within the HAP, (3) determine the effect of islet packing density on the performance of seeded HAPS, (4) determine the glucose- induced insulin response of seeded HAPS perfused with media containing different oxygen concentrations, (5) test for periods of up to 2 months the best HAP configurations in a small group of pancreatectomized rhesus monkeys, and (6) develop comprehensive theoretical models for analysis of the various transport experiments proposed. ***
