In vitro perfusion of hybrid artificial pancreas devices at low flow rates

Type I diabetes is characterized by insulin insufficiency due to lack of functional beta cells. To replace injection therapy, schemes such as the Hybrid Artificial Pancreas (HAP) were developed. This consists of an acrylic housing enclosing a semipermeable hollow fiber membrane. Donor islets can be seeded in the annular space through a port in the housing, and thus are separated from the recipient's bloodstream or perfusate. Before scaling the HAP to human size, the dynamics of its insulin response to a perfusion glucose challenge must be better understood. In this study, the HAP's insulin response after a step increase in the lumenal glucose concentration was determined as a function of the radial thickness of the annular space (0.173-0.973 mm) and islet distribution at a flow rate of 1 ml/min. Devices containing a single, 65 mm long fiber were used. Rat islets were isolated using standard collagenase digestion techniques. In unseeded HAP perfusions, the washout time for glucose and insulin from the annular space was dependent on flow rate and radial thickness. Both solutes were removed in < 3 min from the smallest devices when perfused at 10 ml/min. Thus, solute transport within the HAP is very fast. In the seeded HAP perfusions, the devices were subjected to a step increase in the lumenal glucose concentration. Sequential samples of the HAP effluent were collected and assayed for glucose and insulin. The spatial distribution of the islets in the annular space was one of the most important factors in determining the HAP's insulin response.(ABSTRACT TRUNCATED AT 250 WORDS)