Engineering Synthetic Artificial Pancreas:Design And The Function Of Prolonged Insulin Release

The effective way to treat type I and advanced type II diabetes is real-time sensing the concentration of blood glucose and injecting proper amount of insulin at proper time,but this traditional therapy is painful and inaccurate.Artificial pancreas is a better choice to fast-responsiveness of raised blood glucose and persistence of insulin release.However,combination of these goals in a biocompatible and implantable system is still challenging.The purpose of the present study is to design a scaffold-based engineering synthetic artificial pancreas by integration of chitosan hydrogels with insulin-loaded glucose-responsive microspheres based on Con A-sugar affinity.The obtained scaffold can not only maintain the fast-responsiveness of microspheres for insulin release,but also prolong the release time.The research of this study mainly contains:(1)Use Isothermal Titration Calorimetry to measure the affinity of Con A-glucose and Con A-Dex-GMA to determine the suitable ratio between Con A and Dex-GMA in the microspheres,as the ratio is significant to realize glucose responsiveness;(2)Glucose-responsive insulin-loaded microspheres were fabricated via an emulsion-crosslinking based microfluidic and high-speed shear-emulsion method.Comparing the drug loading capacity,efficiency and degree of solidification,high-speed shear-emulsion method was chosen for further experiments;(3)Use 3D printing and template method to fabricate a scaffold-based synthetic artificial pancreas by integrating insulin-loaded microspheres into chitosan hydrogels.Template method was proved a better way considering the concentration of chitosan,structure of scaffold and drug loading capacity.The results are showing below:(1)In vitro drug release experiments indicated the scaffold exhibited a longer insulin supply and 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;(2)The weight loss profile demonstrated a faster weight loss of integrated scaffold in the first week compared to chitosan-only scaffold;(3)The culture of HDF cells on the scaffold showed good cytocompatibility during 7 days incubation.These results suggested the scaffold-based synthetic artificial pancreas have great promise in the application of insulin delivery.