Microcapsules with improved mechanical stability for hepatocyte culture

Packed-bed or fluidized-bed bioreactor filled with microencapsulated hepatocytes has been proposed as one of the promising designs for bioartificial liver assist device (BLAD) because of potential advantages of high mass transport rate and optimal microenvironment for hepatocyte culture. Recently, we have developed a microcapsule system for the encapsulation of hepatocytes. The microcapsules consist of an inner core of modified collagen and an outer shell of terpolymer of methyl methacrylate, methacrylate and hydroxyethyl methacrylate. Cells encapsulated in these microcapsules exhibit enhanced cellular functions. Improving the mechanical stability of the microcapsules to withstand the shear stress induced by high perfusion rate would be crucial to the success of BLAD applications. In this study, we investigated the effects of terpolymer molecular weight (Mw) on the mechanical property of these microcapsules and the differentiated functions of encapsulated hepatocytes. Six terpolymers with different Mw were synthesized using radical polymerization in solution by adjusting the reaction temperature and the initiator concentration. All the terpolymers formed microcapsules with the methylated collagen. While the terpolymer Mw had little effect on the capsule membrane thickness and permeability of serum albumin, the mechanical property of the microcapsules was significantly improved by the higher Mw of the terpolymer. Differentiated functions of the hepatocytes cultured in the microcapsules, including urea synthesis, albumin synthesis and cytochrome P450 metabolic activity, were not significantly affected by the terpolymer Mw.