Hoque M E, Mao H Q, Ramakrishna S
Department of Mechanical Engineering, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Republic of Singapore.
J Biomater Sci Polym Ed. 2007;18(1):45-58. doi: 10.1163/156856207779146088.
Three-dimensional ex vivo hepatocyte culture is a tissue-engineering approach to improve the treatment of liver disease. The extracorporeal bioartificial liver (BAL) assists devices that are used in patients until they either recover or receive a liver transplant. The 3-D scaffold plays a key role in the design of bioreactor that is the most important component of the BAL. Presently available 3-D scaffolds used in BAL have shown good performance. However, existing scaffolds are considered to be less than ideal in terms of high-density cultures of hepatocytes maintaining long-term metabolic functions. This study aims to develop a 3-D hybrid scaffold for a BAL support system that would facilitate high-density hepatocyte anchorage with long-term metabolic functions. The scaffolds were fabricated by interlacing polyethylene terephthalate (PET) fibers onto the polysulfone hollow fibers utilizing a modern microbraiding technique. Scaffolds with various pore sizes and porosities were developed by varying braiding angle which was controlled by the gear ratio of the microbraiding machine. The morphological characteristics (pore size and porosity) of the scaffolds were found to be regulated by the gear ratio. Smaller braiding angle yields larger pore and higher porosity. On the other hand, a larger braiding angle causes smaller pore and lower porosity. In hepatocyte culture it was investigated how the morphological characteristics (pore size and porosity) of scaffolds influenced the cell anchorage and metabolic functions. Scaffolds with larger pores and higher porosity resulted in more cell anchorage and higher cellular functions, like albumin and urea secretion, compared to that of smaller pores and lower porosity.
三维离体肝细胞培养是一种改善肝病治疗的组织工程方法。体外生物人工肝(BAL)辅助装置用于患者,直至他们康复或接受肝移植。三维支架在生物反应器的设计中起着关键作用,而生物反应器是BAL的最重要组成部分。目前用于BAL的三维支架已显示出良好的性能。然而,就维持长期代谢功能的肝细胞高密度培养而言,现有支架被认为并不理想。本研究旨在开发一种用于BAL支持系统的三维混合支架,该支架将促进具有长期代谢功能的肝细胞高密度锚定。通过使用现代微编织技术将聚对苯二甲酸乙二酯(PET)纤维交织到聚砜中空纤维上来制造支架。通过改变由微编织机的齿轮比控制的编织角度,开发出具有各种孔径和孔隙率的支架。发现支架的形态特征(孔径和孔隙率)受齿轮比调节。较小的编织角度产生较大的孔和较高的孔隙率。另一方面,较大的编织角度导致较小的孔和较低的孔隙率。在肝细胞培养中,研究了支架的形态特征(孔径和孔隙率)如何影响细胞锚定和代谢功能。与较小孔径和较低孔隙率的支架相比,具有较大孔和较高孔隙率的支架导致更多的细胞锚定和更高的细胞功能,如白蛋白和尿素分泌。