An immunoisolating nanoporous alumina biocapsule for the encapsulation of beta cells to treat Type 1 diabetes.

摘要

About 1.5 million people in the U.S. have Type 1 diabetes, an autoimmune disease which specifically destroys the insulin secreting beta cells of the pancreas. Daily insulin injections are the standard treatment for this disease; however, this cannot achieve the same rigorous control over blood glucose that is characteristic of beta cells.; Over the last several decades, considerable research efforts have focused on the development of a bioartificial pancreas using cell encapsulation technology. This approach would provide patients with more physiological blood glucose regulation without the need for immunosuppressive drugs. Polymeric membranes are often used; however, polymers are associated with poor chemical resistance, inadequate mechanical strength, and broad pore size distributions, all of which could jeopardize the integrity of the graft.; The aim of this work was to fabricate and develop a novel immunoisolation device for the treatment of Type 1 diabetes. Immunoisolating biocapsules, comprised of nanoporous alumina, were fabricated with a two-step anodization process that resulted in well-defined and highly controlled features such as pore size, pore size distribution, and membrane thickness. Subsequently, the following objectives were addressed: (1) The immunoisolation potential of the device was assessed by characterizing the diffusion behavior of glucose and IgG through the nanoporous membrane; (2) The viability and insulin secretion of encapsulated beta cells was evaluated, and the effects of packing density, encapsulation time, and membrane configuration on beta cell behavior were also studied; (3) The biocompatibility of the capsule was measured in terms of cytotoxicity, protein adsorption to the material, complement activation, and inflammatory reaction in vivo. The effect of surface modification of the device with poly(ethylene glycol) on the interactions between the material and the host was also tested.; The results showed that nanoporous alumina membranes selectively regulated the diffusion of glucose and IgG, suggesting that they could retain viable cells and simultaneously provide adequate immunoprotection. Encapsulated beta cells maintained viability and insulin secretion, and both packing density and transport area influenced the behavior of the cells. Results from biocompatibility tests demonstrated that the device is non-toxic, does not induce significant complement activation, and causes a transient inflammatory response in vivo.