Engineering synthetic artificial pancreas using chitosan hydrogels integrated with glucose-responsive microspheres for insulin delivery

Abstract

The closed-loop delivery of insulin in response to change of the blood glucose level and long-term supply of insulin are both important for diabetes patients. However, combination of these two goals in a chemically controlled implantable system is still challenging yet highly desirable. The purpose of the present study is to design a synthetic artificial pancreas by integration of chitosan hydrogels with insulin-loaded glucose-responsive microspheres to deliver insulin in a close-looped and long-term way for diabetes care. Glucose-responsive insulin-loaded microspheres were firstly fabricated via a high-speed shear-emulsion based crosslinking method and then embedded into chitosan hydrogels to make a scaffold-based synthetic artificial pancreas. In vitro experiments indicated the scaffold exhibited a longer insulin supply as well as a lower burst release compared with free microspheres, and could keep the glucose-responsive insulin release property inherited from the corresponding microspheres even after 12 day-release. The released insulin was proved to remain active, and the culture of HDF cells on the scaffold showed good cell proliferation during 7 days incubation. These results suggested the scaffold-based synthetic artificial pancreas have great promise in the application of insulin delivery.