Microstructuring ceramic scaffolds for hepatocyte cell culture

Abstract

Both extracorporeal liver support devices and tissue engineering of liver for transplantation require the maintenance of functionality of liver cells (hepatocytes) in cell culture for a long time. One approach to achieve this is to optimize hepatocyte in vitro environment by using a scaffold with topographic structure at sub-millimeter scale which controls cell distribution. Therefore, a set of new type of titania ceramic scaffolds, containing cavities of several sizes, has been produced for deducing the best choice of cavity dimensions for culturing hepatocytes. The aim of this paper is to describe in detail the production methods and characterization of such ceramic scaffolds. Experimental production of the scaffolds consists of microfabrication of silicon templates as well as preparation and molding of titania ceramics. The templates, containing arrays of conical protrusions arranged in close-packed hexagonal order, have been achieved using microfabrication methods of photolithography and anisotropic etching in KOH at 50 degrees C. Protrusion dimensions and overall quality of the templates has been evaluated by scanning electron microscopy. The microfabricated templates have resulted in well-defined and reproducible cavities of corresponding dimensions on the titania ceramic surface after injection-molding. Alternatively, simple embossing of the plastified green ceramics with the silicon templates attached to a metal plate also creates cavities on the ceramic surface. While both methods yield good results, they have different advantages: the injection-molding provides a higher quality of imprints while embossing is quicker and less complicated, and is not limited by dimensions of specific molding equipment.