Wang Ting, Feng Zhang-Qi, Leach Michelle K, Wu Jinghang, Jiang Qing
Affiliated Hospital, Clinical Trials Center, Jinan University, Guangzhou, 510632, China.
J Mater Chem B. 2013 Jan 21;1(3):339-346. doi: 10.1039/c2tb00195k. Epub 2012 Nov 12.
Advanced scaffold materials are required for liver tissue engineering, to improve primary hepatocyte activity and hepatic function in vitro. The nanotopography of the scaffold material plays an important role in the regulation of cell growth and function. Therefore, in the current study, we developed a novel scaffold composed of type-I collagen coated nanoporous poly(l-lactic acid) (PLLA) fibers (nPFs) to provide a nanotopography with a combination of fibrous and porous features for the culture of primary hepatocytes. The interaction between the nanotopography and the hepatocytes was described by testing cell morphology, retention, activity and hepatic function over a 15 day culture period. Primary hepatocytes cultured on the nPFs formed large-area stable immobilized monolayers after 3 days of culture, and displayed excellent cell bioactivity with higher levels of liver-specific function maintenance, in terms of albumin secretion, urea synthesis, and CYP1A and UGT enzymatic activity, than those cultured on type-I collagen coated non-porous PLLA fibers (Fs). These results indicate that the combined fibrous and porous nanotopography of nPFs has a superior promoting effect on primary hepatocyte culture compared to the non-porous fibrous nanotopography of Fs. The nPFs may be a suitable material for liver tissue engineering research and potential therapeutic applications, such as in bioartificial liver devices, and as a substrate for primary hepatocyte culture.
肝脏组织工程需要先进的支架材料,以提高原代肝细胞在体外的活性和肝功能。支架材料的纳米拓扑结构在调节细胞生长和功能方面起着重要作用。因此,在本研究中,我们开发了一种新型支架,其由I型胶原包被的纳米多孔聚(L-乳酸)(PLLA)纤维(nPFs)组成,为原代肝细胞培养提供具有纤维和多孔特征组合的纳米拓扑结构。通过在15天的培养期内测试细胞形态、滞留率、活性和肝功能来描述纳米拓扑结构与肝细胞之间的相互作用。在nPFs上培养的原代肝细胞在培养3天后形成大面积稳定的固定化单层,并且在白蛋白分泌、尿素合成以及CYP1A和UGT酶活性方面,显示出比在I型胶原包被的无孔PLLA纤维(Fs)上培养的细胞具有更高水平的肝脏特异性功能维持能力,具有优异的细胞生物活性。这些结果表明,与Fs的无孔纤维纳米拓扑结构相比,nPFs的纤维和多孔纳米拓扑结构组合对原代肝细胞培养具有更好的促进作用。nPFs可能是肝脏组织工程研究和潜在治疗应用(如生物人工肝装置以及作为原代肝细胞培养的基质)的合适材料。