| Immunoisolation of transplanted tissue shows promise for the treatment of a number of diseases. This technique uses permselective membranes to prevent the destruction of the transplanted tissue by the host's immune system. A number of different permselective membranes have been tried for the encapsulation of islets of Langerhans, the tissue responsible for maintenance of the glucose concentration in the blood of mammals. These membranes have shown the proof of principal of islet encapsulation for the treatment of diabetes in small animals, however, improvements in the materials and techniques are necessary.; Photopolymerizable poly (ethylene glycol) (PEG), a polymer widely used in the biomedical industry as a biocompatible polymer, shows promise for use as a permselective membrane for islet transplantation. Photoactivity of PEG is conferred by the acrylation of the terminal alcohols of PEG. A new scheme of acrylation of PEG has been determined, leading to increased acrylation substitution and product purity, as determined by NMR, GPC, and FTIR. Additionally, hydrogels made from these materials have undergone biocompatibility testing in Sprague Dawley rats. The tissue response to these materials has been shown to be limited to a single layer of quiescent macrophages.; Permselective PEG diacrylate hydrogels have been synthesized using bulk phase and interfacial phase photoinitiation. Microspheres containing islets, made from bulk phase initiation, were implanted into diabetic athymic mice, Sprague Dawley rats, and rabbits. In each animal model, an initial drop in blood glucose concentrations was observed, however a return to hyperglycemia was observed within 10 d. The bulk phase experiments were performed using PEG diacrylates synthesized using a non-optimized reaction and purification scheme, potentially explaining the poor in vivo results.; A sensitivity study of six key variables in the interfacial photopolymerization process was performed to aid in determination of the optimal encapsulation conditions, leading to the most uniform hydrogel membranes and viable islets. Interfacially encapsulated islets were transplanted into diabetic athymic mice for correction studies and into Sprague Dawley rats for survival studies. Long term maintenance of normoglycemia was observed in diabetic athymic mice and long term survival of porcine islets in a disconcordant xenograft model was observed. |
