Journal article
Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids
Lab on a chip, Vol.18(17), pp.2547-2562
09/07/2018
DOI: 10.1039/c8lc00333e
PMID: 30019731
Abstract
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.
Details
- Title: Subtitle
- Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids
- Creators
- Li-Dong Ma - Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, State Key Lab Qual Res Chinese Med, Macau, Peoples R ChinaYi-Tong Wang - Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, State Key Lab Qual Res Chinese Med, Macau, Peoples R ChinaJing-Rong Wang - Macau University of Science and TechnologyJian-Lin Wu - Macau University of Science and TechnologyXian-Sheng Meng - Liaoning University of Traditional Chinese MedicinePing Hu - East China University of Science and TechnologyXuan Mu - Tufts UniversityQiong-Lin Liang - Tsinghua UniversityGuo-An Luo - Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
- Resource Type
- Journal article
- Publication Details
- Lab on a chip, Vol.18(17), pp.2547-2562
- Publisher
- Royal Soc Chemistry
- DOI
- 10.1039/c8lc00333e
- PMID
- 30019731
- ISSN
- 1473-0197
- eISSN
- 1473-0189
- Number of pages
- 17
- Grant note
- 2017YFC1700800 / Special Project on Modernization of Traditional Chinese Medicine of National Priority Research Project of the Ministry of Science and Technology (MOST) in China 089/2013/A3; 129/2017/A3 / Macau Science and Technology Development Fund
- Language
- English
- Date published
- 09/07/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering
- Record Identifier
- 9984276454602771
Metrics
89 Record Views