Evaluation of Encapsulating and Microporous Non-degradable Hydrogel Scaffold Designs on Islet Engraftment in Rodent Models of Diabetes

• Published in: Biotechnology and bioengineering Vol. 115; no. 9; pp. 2356 - 2364
• Main Authors: Rios, Daniel Peter, Skoumal, Michael, Liu, Jeffrey, Youngblood, R., Kniazeva, Ekaterina, Garcia, Andrés J., Shea, Lonnie D.
• Format: Journal Article
• Language: English
• Published: 25.06.2018
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.26741

Islet transplantation is a promising therapeutic option for Type 1 diabetes mellitus, yet the current delivery into the hepatic portal vasculature is limited by poor engraftment. Biomaterials have been employed as a means to promote engraftment and function at extrahepatic sites, with strategies being categorized as encapsulation or microporous scaffolds that can either isolate or integrate islets with the host tissue, respectively. While these approaches are typically studied separately using distinct material platforms, herein, we developed non-degradable polyethylene glycol (PEG)-based hydrogels for islet encapsulation or as microporous scaffolds for islet seeding in order to compare the initial engraftment and function of islets in syngeneic diabetic mice. Normoglycemia was restored with transplantation of islets within either encapsulating or microporous hydrogels containing 700 islet equivalents (IEQ), with transplantation on microporous hydrogels producing lower blood glucose levels at earlier times. A glucose challenge test at one month post-transplant indicated that encapsulated islets had a delay in glucose-stimulated insulin secretion, whereas microporous hydrogels restored normoglycemia in times consistent with native pancreata. Encapsulated islets remained isolated from the host tissue, whereas the microporous scaffolds allowed for re-vascularization of the islets post-transplant. Finally, we compared the inflammatory response post-transplantation for the two systems, and noted that microporous hydrogels had a substantially increased presence of neutrophils. Collectively, these findings suggest that both encapsulation and microporous PEG scaffold designs allow for stable engraftment of syngeneic islets and the ability to restore normoglycemia, yet the architecture influences islet function and responsiveness following transplantation.