Chapter 21 - Conformal coating

Abstract

Encapsulation of islets of Langerhans is a promising strategy to enable immunosuppression-free islet transplantation to cure autoimmune diabetes. Traditional encapsulation platforms based on the electrostatic droplet generation of hydrogel-based microcapsules have demonstrated safety of islet encapsulation but have not yielded clinical success yet despite over 30years of research. Failure of microencapsulated islet grafts is likely due to the large barrier to diffusion presented by the ~1mm in diameter capsules, there resulting sizeable graft volumes, and the instability of commonly employed hydrogel platforms. A new conformal coating technology was developed to address these limitations of conventional microencapsulation. Conformal coating is the encapsulation of islets in a thin (few tens of microns) layer of hydrogel, where the coating thickness is not a function of islet diameter. So, islets of 50–500μm diameter are coated with hydrogels of constant thickness of few tens of microns. Conformal coatings are achieved by flow focusing and subsequent jet breakup of the islet/pregel polymer slurry, as defined by the Plateau-Rayleigh instability. The conformal coating technology facilitates a vast reduction in graft volumes, which in turn permits transplantation of encapsulated islets in confined and well-vascularized sites such as the omentum. Further, hydrogels used in conformal coating employ covalent cross-linking methods which result in biostable and bioinert hydrogel coatings. Conformal coating has been shown to be applicable to differently sourced islets, including human islets and to protect transplanted allogeneic islets from immune recognition resulting in long-term diabetes reversal in an immunocompetent mouse model.