Synthetic poly(ethylene glycol)-based microfluidic islet encapsulation reduces graft volume for delivery to highly vascularized and retrievable transplant site.

Transplantation of hydrogel-encapsulated allogeneic islets has been explored to reduce or eliminate the need for chronic systemic immunosuppression by creating a physical barrier which prevents direct antigen presentation. Although successful in rodents, translation of alginate microencapsulation to large animals and humans has been hindered by large capsule sizes (≥500 μm diameter) that result in suboptimal nutrient diffusion in the intraperitoneal space. We developed a microfluidic encapsulation system which generates synthetic poly(ethylene glycol) (PEG)-based microgels with smaller diameters (310 ± 14 μm) that improve encapsulated islet insulin responsiveness over alginate capsules and allow transplantation within vascularized tissue spaces, thereby reducing islet mass requirements and graft volumes. By delivering PEG encapsulated islets to an isolated, retrievable, and highly vascularized site via a vasculogenic delivery vehicle, we demonstrate that a single pancreatic donor syngeneic islet mass exhibits improved long term function over conventional alginate capsules and close integration with transplant site vasculature. In vivo tracking of bioluminescent allogeneic encapsulated islets in an autoimmune type 1 diabetes murine model showed enhanced cell survival over unencapsulated islets in the absence of chronic systemic immunosuppression. This method demonstrates a translatable alternative to intraperitoneal encapsulated islet transplantation. This article is protected by copyright. All rights reserved.