VEGF-conjugated alginate hydrogel prompt angiogenesis and improve pancreatic islet engraftment and function in type 1 diabetes

Type 1 diabetes was a life-long disease that affected numerous people around the world. Insulin therapy has its limitations that may involve hyperglycemia and heavy burden of patient by repeated dose. Islet transplantation emerged as a promising approach to reach periodical reverse of diabetes, however, transplanted islets suffer from foreign body reaction and lack of nutrition and oxygen supply, especially in the blood-vessel-shortage subcutaneous site which was preferred by patient and surgeon. In this study, we designed and synthesized a vascular endothelial growth factor (VEGF) conjugated alginate material to encapsulate the transplanted islets via 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) reaction, and successful conjugation was confirmed by Nuclear Magnetic Resonance H1 spectrum. The best VEGF concentration (100 ng/ml) was determined by the combined studies of the mechanical property and endothelial cell growth assay. In vivo study, conjugated VEGF on alginate exhibited sustained promoting angiogenesis property after subcutaneous transplantation by histology study and islets encapsulated in this material achieved long term therapeutic effect (up to 50 days) in the diabetic mice model. In conclusion, this study establishes a simple biomaterial strategy for islet transplantation to enhance islet survival and function, which could be a feasible therapeutic alternative for type 1 diabetes. (C) 2016 Elsevier B.V. All rights reserved.