Multilayered heparin hydrogel microwells for cultivation of primary hepatocytes.

Multilayered heparin hydrogel microwells for cultivation of primary hepatocytes.
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多层肝素水凝胶微孔用于培养原发性肝细胞。

DOI:
10.1002/adhm.201300054
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发表时间:
2014-01
影响因子:
10
通讯作者:
Revzin, Alexander
Revzin, Alexander
中科院分区:
工程技术1区
文献类型:
--
作者:
You, Jungmok;Shin, Dong-Sik;Patel, Dipali;Gao, Yandong;Revzin, Alexander

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用于再生医学的生物材料支架需要进行合理的设计,以实现预期的细胞命运和功能。本文介绍了用于原代肝细胞培养的水凝胶微结构的研究进展。测试了四种不同的微图案化表面:1)在玻璃上图案化的聚乙二醇微孔,2)在玻璃上图案化的肝素水凝胶微孔,3)在肝素水凝胶涂层基板上图案化的聚乙二醇微孔,以及4)在肝素水凝胶涂层基板上图案化的肝素水凝胶微孔。后者的表面由微模塑和微接触印刷技术相结合来构建,以创建具有由肝素水凝胶组成的壁和地板的微孔。单个微孔的直径为200μm,高度为20μm。在所有情况下,微孔的底部都被I型胶原修饰以促进细胞黏附。肝细胞培养和肝脏标志物(尿素生成、白蛋白合成和E-钙粘素表达)分析表明,全肝素凝胶微孔最有利于维持肝脏表型。例如,ELISA分析显示,与其他微图案表面相比,全肝素凝胶井中的白蛋白产量高出2.3至13.1倍。重要的是,通过在微孔的肝素凝胶壁上培养成纤维细胞,可以进一步提高肝脏表型的表达。未来,多组分全肝素凝胶微结构可能被用于设计肝脏干细胞肝脏特异性分化的利基环境。
The biomaterial scaffolds for regenerative medicine need to be rationally designed to achieve the desired cell fate and function. This paper describes the development of hydrogel microstructures for cultivation of primary hepatocytes. Four different micropatterned surfaces are tested: 1) poly(ethyelene glycol) (PEG) microwells patterned on glass, 2) heparin hydrogel microwells patterned on glass, 3) PEG microwells patterned on heparin hydrogel-coated substrates, and 4) heparin hydrogel microwells patterned on heparin hydrogelcoated substrates. The latter surfaces are constructed by a combination of micromolding and microcontact printing techniques to create microwells with both walls and floor composed of heparin hydrogel. Individual microwell dimensions are 200 μm diameter and 20 μm in height. In all cases, the floor of the microwells is modified with collagen I to promote cell adhesion. Cultivation of hepatocytes followed by analysis of hepatic markers (urea production, albumin synthesis, and E-cadherin expression) reveals that the all-heparin gel microwells are most conducive to hepatic phenotype maintenance. For example, ELISA analysis shows 2.3 to 13.1 times higher levels of albumin production in all-heparin gel wells compared with other micropatterned surfaces. Importantly, hepatic phenotype expression can be further enhanced by culturing fibroblasts on the heparin gel walls of the microwells. In the future, multicomponent all-heparin gel microstructures may be employed in designing hepatic niche for liver-specific differentiation of stem cells.
DOI: 10.1021/la803635r
发表时间: 2009-04-09
期刊: Langmuir : the ACS journal of surfaces and colloids
影响因子: --
作者:
Lee JY;Shah SS;Yan J;Howland MC;Parikh AN;Pan T;Revzin A
通讯作者: Revzin A
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发表时间: 2009-11-01
影响因子: 6.7
作者:
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发表时间: 2005-01-01
期刊: LAB ON A CHIP
影响因子: 6.1
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发表时间: 2006-10-01
期刊: BIOMATERIALS
影响因子: 14
作者:
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通讯作者: Langer, Robert
DOI: 10.1021/bp00009a007
发表时间: 1991-05-01
影响因子: 2.9
作者:
DUNN, JCY;TOMPKINS, RG;YARMUSH, ML
通讯作者: YARMUSH, ML