(462g) A Biodegradable, Immunoprotective, Dual Nanoporous Capsule for Cell-Based Therapies

Immunoprotection of transplanted cells and tissue by size-based semipermeable membranes is an attractive approach for cell-based therapy to treat patients with such diseases as diabetes mellitus,Parkinson's disease, Alzheimer's, etc. Such cell-based devices are thought to hold great promise in applications requiring site-specific and sustainable drug delivery of cell-synthesized molecules. To demonstrate the transplantation of drug-secreting cells, an integrated biodegradable delivery device combining two nanoporous capsules is developed using the betaTC-6 cell line as a model system. The outer capsule is a poly (å-caprolactone) (PCL) reservoir covered with a nanoporous membrane made by phase inversion technique. TC-6 cells encapsulated in alginate-poly-L-lysion (AP) microcapsules are placed in the PCL capsule. Biodegradable nanoporous membranes were investigated for their effects on survival, proliferation, and differentiation of the TC-6 cell line. In AP microcapsules, sufficient nutrient diffusion could allow TC-6 cells inside microcapsules to maintain their normal growth. Both nanoporous capsules also showed good immunoprotection in the IgG solution. As an insulin-secreting cell line, TC-6 cells can release significant quantities of insulin for the treatment of diabetes. The controlled release of insulin from this integrated device was indirectly evaluated in vitro by monitoring the glucose concentration. This integrated device could achieve multi-functionalities for cell-based therapy: a 3-D microenvironment provided by microcapsule for cell growth, superior immunoprotection and controllable release performance provided by the two nanoporous capsules.