Improving mechanical stability and density distribution of hepatocyte microcapsules by fibrin clot and gold nano-particles.

Bio-artificial livers (BAL) with microencapsulated hepatocytes have the typical limitations in maintaining hepatocyte functions, mechanical stability and uniform perfusion in packed or fluidized-bed bioreactors. We have previously developed microcapsules with enhanced hepatocyte functions. Here we have introduced a fibrin network inside microcapsules by (1) mixing collagen and fibrinogen with the encapsulated hepatocytes to support the cells; (2) submerging the microcapsules into a thrombin solution to induce the formation of an insoluble fibrin network inside the microcapsules. Fracture analysis on the microcapsules revealed significant improvement in mechanical stability. We have also introduced different amounts of gold nano-particles into microcapsules to achieve different densities for uniform bioreactor perfusion. These gold nano-particles also improved the mechanical stability of the microcapsules. Both the fibrin network and gold nano-particles exhibited the additional benefits of enhancing certain bio-functions of the encapsulated hepatocytes. The applications of these improved microcapsules in the development of bio-artificial livers are discussed.