Grant: Travel Awards - Institute Community Support

Objective: Closed-loop insulin delivery systems offer diabetic patients improved glycemic control, compliance and quality of life, however long-term efficacy has yet to be demonstrated due to poor device biocompatibility. Sustained administration of anti-inflammatory agents may improve device lifetime, however such strategies are accompanied with side-effects and difficult to implement. We demonstrate prolonged functional lifetime of a chemically-driven closed-loop insulin delivery implant by passively impeding cell migration to the implant surface using a microfabricated microporous membrane. Methods: Polymeric membranes featuring micron-sized pores were constructed using soft-lithography and affixed overtop of a chemically-driven closed-loop insulin delivery system comprised of an insulin reservoir sealed with a variable-porosity glucose-responsive albumin plug. Devices with and without the microporous membrane were implanted subcutaneously in healthy rats and assessed for tissue biocompatibility over 30 days. Device efficacy was assessed in a diabetic rat model. Blood insulin, glucose, and c-peptide levels were measured for 30 days. Result: Microporous membranes minimized accumulation of cells at the glucose-responsive plug surface and subsequent cell-mediated degradation compared to unprotected devices. The membranes further resulted in resolution of the inflammatory process to the implant as evidenced by minimal residual perivascular lymphocytic and histocytic inflammation, absence of neutrophils at the implant site, and a thinner fibrous capsule by day 30 following implantation. Finally, use of the microporous membranes successfully prolonged the in vivo efficacy duration by up to 3-fold (28 days) compared to unprotected devices. Conclusion: Microfabricated microporous membranes act as a barrier to cell migration to the immunogenic surface of a chemically driven closed-loop insulin delivery device, thereby improving implant lifetime.