Microfabricated microporous membranes reduce the host immune response and prolong the functional lifetime of a closed-loop insulin delivery implant in a type 1 diabetic rat model.

Implantation of a medical implant within the body inevitably triggers a host inflammatory response that negatively impacts its function and longevity. Nevertheless, the degree and severity of this response may be reduced by selecting appropriate materials, implant geometry, surface topography and surface treatment. Here we demonstrate a strategy to improve the biocompatibility of a chemically-driven closed-loop insulin delivery implant.

In vivo performance and biocompatibility of a subcutaneous implant for real-time glucose-responsive insulin delivery.

An implantable, glucose-responsive insulin delivery microdevice was reported previously by our group, providing rapid insulin release in response to hyperglycemic events and efficacy in vivo over a 1-week period when implanted intraperitoneally in rats with diabetes. Herein, we focused on the improvement of the microdevice prototype for long-term glycemic control by subcutaneous (SC) implantation, which allows for easy retrieval and replacement as needed. To surmount the strong immune response to the SC implant system, the microdevice was treated by surface modification with high-molecular-weight polyethylene glycol (PEG).

In vitro and in vivo testing of glucose-responsive insulin-delivery microdevices in diabetic rats.

We have developed glucose-responsive implantable microdevices for closed-loop delivery of insulin and conducted in vivo testing of these devices in diabetic rats. The microdevices consist of an albumin-based bioinorganic membrane that utilizes glucose oxidase (GOx), catalase (CAT) and manganese dioxide (MnO(2)) nanoparticles to convert a change in the environmental glucose level to a pH stimulus, which regulates the volume of pH-sensitive hydrogel nanoparticles and thereby the permeability of the membrane. The membrane is integrated with microfabricated PDMS (polydimethylsiloxane) structures to form compact, stand-alone microdevices, which do not require tethering wires or tubes.