| An encapsulation device based on microfabrication technology for the delivery of insulin secreting pancreatic beta cells was developed and evaluated. The transplantation of encapsulated cells is a promising therapy for the treatment of pathologies such as Type I diabetes, Parkinson's, chronic pain and hemophilia. Tissue and cell transplantation, however, require life-long immunosuppressive therapy to protect the graft from the host immunoresponse. The research presented in this dissertation investigated whether microfabricated silicon-based biocapsules with uniform pore size ranging from 7 nm to 49 nm could provide encapsulated cells with an immunoisolated environment able to maintain physiologic viability, morphology and function.; By utilizing bulk and surface micromachining techniques commonly employed in the microelectronics industry (MEMS), nanoporous membranes with precise features were engineered. Because the biocapsule is a diffusion based device, mass transfer of relevant biomolecules such as glucose, albumin, and immunoglobulin G across the membrane was characterized. In vitro and in vivo tests were conducted to establish the biocapsule biocompatibility and poly(ethylene glycol) surface coating was considered as a tool to modulate in vivo tissue response.; In order to improve the device overall performance, particular attention was devoted to engineering the intracapsular environment. Three-dimensional matrices were introduced to achieve uniform cell distribution, avoid the formation of excessive cell clusters and minimize diffusion barriers therefore improving long-term cell viability. Providing the cells with an extracellullar matrix was also investigated as a means to induce cell differentiation and control insulinoma cell proliferation within the capsule.; To achieving a more extensive and non-invasive characterization of the intracapsular environment, a manganese-enhanced magnetic resonance microimaging technique was developed. The system employed was sensitive enough to discern single activated islets and could potentially be applied as a generic method for the non-invasive imaging of insulin secreting beta cells.; Overall, the findings presented in this work suggest that the semipermeability and biocompatibility of the biocapsule together with a careful engineered intracapsular environment may provide an improved immunoisolation device for cell-based therapies. More specifically, although much work is still needed, it is believed that these advances could be critical in the development of a successful bioartificial pancreas. |
