Engineering a Porous Hydrogel-Based Device for Cell Transplantation.

Abstract

Islet cell transplantation in encapsulation devices provides a potential means of treatment for type 1 diabetes. However, such devices pose challenges that must be addressed. Most current encapsulating devices are not scalable and lack retrievability which limit their potential clinical applications. Here, a translatable cell encapsulation device, which is porous, flexible, scalable, and retrievable, is reported. The device is fabricated from processable tough hydrogels (water content >400%), which are extremely tough (>1000 J m-2), yet soft (modulus ∼250-1000 kPa), and highly stretchable (up to 1000%). A facile method is introduced to render hydrogels porous (up to 60%) and control their pore size (∼150-600 μm). Human insulin-producing pancreatic β-cell lines and porcine neonatal islet cell clusters are incorporated into the pores of the tough hydrogel device with in vitro biocompatibility studies revealing no cytotoxic effects. Viability staining, insulin protein expression, and in vitro glucose-stimulated insulin secretion of the encapsulated β-cell lines and islets indicate high viability and desired metabolic and endocrine function. Our findings provide a proof-of-concept for the scalable manufacturing of retrievable, hydrogel-based devices with porous structures to facilitate the transplantation of cells without interfering with the cells' function.