Immune cell recognition of implanted biomedical devices initiate a cascade of inflammatory events that result in collagenous encapsulation of implanted materials which leads to device failure. These adverse outcomes emphasize the critical need for biomaterials that do not elicit foreign body responses. One prime example for the use of this technology is with the development of a bioartificial pancreas for the treatment of patients suffering from diabetes. Immunoisolation of insulin producing cells with porous biomaterials provide an immune barrier that is a potentially viable treatment strategy for Type1 diabetic patients. However, clinical implementation has been challenging due to host immune responses to implanted materials. To address this challenge, we have focused our efforts on the development of improved biomaterials for the use in pancreatic islet cell transplantation.
To enable the discovery of novel superbiocompatible biomaterials we have developed a high throughput pipeline for the synthesis and evaluation of >1000 material formulations and prototype devices. Here, we describe combinatorial methods we have developed for covalent chemical modification and in vivo evaluation of alginate based hydrogels. Using these methods, we have created and screened the first large library of hydrogels, and identified leads that are able to resist foreign body reactions in both rodents and nonhuman primates. These formulations have been used to generate optimized porous alginate hydrogels fabricated with tuned geometries to enhance biocompatibility. Significantly, our lead formulation has enabled us to achieve the first long-term glycemic correction of diabetic animals without immunosuppression using stem cell derived human islets.