Sun T, Chan M L H, Quek C H, Yu H
Molecular and Biomaterials Laboratory, Institute of Materials Research and Engineering, 3 Research Link, Singapore 117602, Singapore.
J Biotechnol. 2004 Jul 15;111(2):169-77. doi: 10.1016/j.jbiotec.2004.02.018.
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.
具有微囊化肝细胞的生物人工肝（BAL）在维持肝细胞功能、机械稳定性以及在填充式或流化床生物反应器中的均匀灌注方面存在典型局限性。我们之前已开发出具有增强肝细胞功能的微囊。在此，我们通过以下方式在微囊内部引入了纤维蛋白网络：（1）将胶原蛋白和纤维蛋白原与被包封的肝细胞混合以支持细胞；（2）将微囊浸入凝血酶溶液中以诱导在微囊内部形成不溶性纤维蛋白网络。对微囊的断裂分析表明其机械稳定性有显著提高。我们还将不同量的金纳米颗粒引入微囊中，以实现不同密度从而进行均匀的生物反应器灌注。这些金纳米颗粒也提高了微囊的机械稳定性。纤维蛋白网络和金纳米颗粒都展现出增强被包封肝细胞某些生物功能的额外益处。本文讨论了这些改良微囊在生物人工肝开发中的应用。
