Engineered VEGF-releasing PEG–MAL hydrogel for pancreatic islet vascularization

• Published in: Drug delivery and translational research Vol. 5; no. 2; pp. 125 - 136
• Main Authors: Phelps, Edward A., Templeman, Kellie L., Thulé, Peter M., García, Andrés J.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2015
• Subjects: Alginates - chemistry; Animals; Biomedical and Life Sciences; Biomedicine; Collagen - chemistry; Glucuronic Acid - chemistry; Hexuronic Acids - chemistry; Hydrogels - administration & dosage; Hydrogels - chemistry; Intestine, Small - blood supply; Intestine, Small - drug effects; Intestine, Small - physiology; Islets of Langerhans - blood supply; Islets of Langerhans - drug effects; Islets of Langerhans - physiology; Islets of Langerhans Transplantation; Male; Maleimides - chemistry; Mesentery - drug effects; Mesentery - physiology; Neovascularization, Physiologic - drug effects; Pharmaceutical Sciences/Technology; Polyethylene Glycols - chemistry; Rats, Inbred Lew; Research Article; Vascular Endothelial Growth Factor A - administration & dosage; Vascular Endothelial Growth Factor A - chemistry; Angiogenesis; PEG; Matrix; VEGF; Mesentery; Islet; Vascularization
• ISSN: 2190-393X; 2190-3948
• DOI: 10.1007/s13346-013-0142-2

Biofunctionalized polyethylene glycol maleimide (PEG–MAL) hydrogels were engineered as a platform to deliver pancreatic islets to the small bowel mesentery and promote graft vascularization. VEGF, a potent stimulator of angiogenesis, was incorporated into the hydrogel to be released in an on-demand manner through enzymatic degradation. PEG–MAL hydrogel enabled extended in vivo release of VEGF. Isolated rat islets encapsulated in PEG–MAL hydrogels remained viable in culture and secreted insulin. Islets encapsulated in PEG–MAL matrix and transplanted to the small bowel mesentery of healthy rats grafted to the host tissue and revascularized by 4 weeks. Addition of VEGF release to the PEG–MAL matrix greatly augmented the vascularization response. These results establish PEG–MAL engineered matrices as a vascular-inductive cell delivery vehicle and warrant their further investigation as islet transplantation vehicles in diabetic animal models.