Multilayered Freestanding Porous Polycarbonate Nanosheets with Directed Protein Permeability for Cell-Encapsulated Devices.

Abstract

Implantable pancreatic β cell-encapsulated devices are required for the treatment of type 1 diabetes. Such devices should enable a semipermeable membrane to release insulin in response to glucose levels while avoiding immune reactions. Micrometer-thick track-etched porous polycarbonate (PC) membranes have been used for this purpose. However, the immediate release of insulin remains a challenge in the development of such semipermeable membranes. Herein, we attempted to develop a freestanding polymeric ultrathin film (nanosheet) with a porous structure that can be used in a cell-encapsulated device. Specifically, we fabricated a nonbiodegradable, porous PC nanosheet to enhance molecular permeability. The nanosheet was multistacked to ensure the controlled permeability of proteins of various molecular weights, such as insulin and IgG. The porous PC nanosheet was prepared by gravure coating using a blend solution comprising PC and polystyrene (PS) to induce macro-phase separation of the PC and PS. When the PC:PS weight ratio of the mixture was reduced to 3:1, we succeeded in fabricating a porous PC nanosheet (thickness: 100 nm, diameter: < 2.5 μm). A triple layer of such porous nanosheets with various pore sizes demonstrated 10 times less protein clogging, 10 times higher insulin permeability, and comparable IgG-blocking capability compared with commercially available porous PC membranes (thickness: 10 μm). Finally, we demonstrated that a cell-encapsulated device equipped with the multilayered porous PC nanosheet as a permeable membrane preserved the glucose response level of insulin-producing cells before, during, and after the cell-encapsulation process. We believe that cell-encapsulated devices equipped with such porous PC nanosheets will enable immediate insulin release in response to changes in glucose levels.