文献类型：期刊文献

英文题名：Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids

作者：Ma, Li-Dong[1];Wang, Yi-Tong[1];Wang, Jing-Rong[1];Wu, Jian-Lin[1];Meng, Xian-Sheng[2];Hu, Ping[3];Mu, Xuan[4];Liang, Qiong-Lin[5];Luo, Guo-An[1,5]

机构：[1]Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, State Key Lab Qual Res Chinese Med, Macau, Peoples R China;[2]Liaoning Univ Tradit Chinese Med, Sch Pharm, Dalian 116600, Peoples R China;[3]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China;[4]Tufts Univ, Dept Biomed Engn, 4 Colby St, Medford, MA 02155 USA;[5]Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China

年份：2018

卷号：18

期号：17

外文期刊名：LAB ON A CHIP

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000443279400005)】；

基金：This work was supported by the Macau Science and Technology Development Fund (Project No. 089/2013/A3 and 129/2017/A3) and the Special Project on Modernization of Traditional Chinese Medicine of National Priority Research Project of the Ministry of Science and Technology (MOST) in China (Project No. 2017YFC1700800).

语种：英文

摘要：Spheroid-based three-dimensional (3D) liver culture models, offering a desirable biomimetic microenvironment, are useful for recapitulating liver functions in vitro. However, a user-friendly, robust and specially optimized method has not been well developed for a convenient, highly efficient, and safe in situ perfusion culture of spheroid-based 3D liver models. Here, we have developed a biomimetic and reversibly assembled liver-on-a-chip (3D-LOC) platform and presented a proof of concept for long-term perfusion culture of 3D human HepG2/C3A spheroids for building a 3D liver spheroid model. On the basis of a fast and reversible seal of concave microwell-based PDMS-membrane-PDMS sandwich multilayer chips, it enables a high-throughput and parallel perfusion culture of 1080 cell spheroids in a high mass transfer and low fluid shear stress biomimetic microenvironment as well as allowing the convenient collection and analysis of the cell spheroids. In terms of reducing spheroid loss and maintaining cell morphology and viability in long-term perfusion culture, the cell spheroids in the 3D-LOC were more safe and efficient. Notably, the polarisation, liver-specific functions, and metabolic activity of the cell spheroids in 3D-LOC were also remarkably improved and exhibited better long-term maintenance over conventional perfusion methods. Additionally, a robust micromilling method that incorporates secondary PDMS coating techniques (SPCs) for fabricating V-shaped concave microwells was also developed. The V-shaped concave microwell arrays exhibited a higher distribution density and aperture ratio, making it easy to form large-scale and uniform-sized cell spheroids with minimum cell loss. In summary, the proposed 3D-LOC could provide a convenient and robust solution for the long-term safe perfusion culture of hepatic spheroids and be beneficial for a variety of potential applications including development of bio-artificial livers, disease modeling, and drug toxicity screening.