(373w) Benign, Permselective Encapsulation of Porcine Islets: Active Nanomaterials Solutions for Xenotransplantation
Transplantation of islets of Langerhans is an attractive treatment for type I diabetes. However, human donor shortages, graft failure, and the necessity for life-long immunosuppression therapy are some of the issues affecting this therapy. Porcine islets have shown promise as an alternative islet supply to alleviate donor shortages but immunosuppression therapy is still necessary. It has been recognized that the encapsulation of living cells with permselective membranes could dramatically improve the viability of transplantation through immunoisolation and decrease the need for immunosuppression therapy. The ideal permselective membrane would simultaneously protect the cell from immunological attack, efficiently transport nutrients, and rapidly release therapeutic cell metabolites (e.g., insulin). Living cell encapsulation (e.g., islet) has included use of biopolymers (i.e. alginate, agarose), polyelectrolyte multilayers, silica sol-gels, poly (ethylene glycol) (PEG), and composites of these materials. However, many of the techniques lack pore size control and greatly increase the total volume of the transplanted graft. In this study, we first show the benign synthesis of small, fluorescent, and monodispersed silica nanoparticles with tunable surface potential. The relatively low cytotoxicity of silica nanoparticles has enabled their use in multiple biological applications. By tuning the surface potential of the silica nanoparticles to a positive charge, we show that the particles are able to assemble on the surface of living cell membranes by simple adsorption. Utilizing layer-by-layer deposition, the particles are controllably assembled on the cell surface to build a thin nanoparticle membrane. Confocal and electron microscopy characterize the deposition of the nanoparticles on the surface of the cells and illustrate that, although the surface of the cell is dynamic and complex, the silica nanoparticles are deposited in a tunable and predictable fashion. The encapsulation protocol was shown to exhibit limited toxicity towards the cells, determined by a MTT viability assay. These findings highlight the potential of these nanoparticles for living cell encapsulation.