Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan, 30013, ROC.
Biomedical Technology and Device Research Laboratories, Industrial Technology of Research Institute, Hsinchu, 300, Taiwan.
Adv Mater. 2017 Sep;29(36). doi: 10.1002/adma.201701545. Epub 2017 Jul 21.
The considerable advances that have been made in the development of organotypic cultures have failed to overcome the challenges of expressing tissue-specific functions and complexities, especially for organs that require multitasking and complex biological processes, such as the liver. Primary liver cells are ideal biological building blocks for functional organotypic reconstruction, but are limited by their rapid loss of physiological integrity in vitro. Here the concept of lattice growth used in material science is applied to develop a tissue incubator, which provides physiological cues and controls the 3D assembly of primary cells. The cues include a biological growing template, spatial coculture, biomimetic radial flow, and circulation in a scaffold-free condition. The feasibility of recapitulating a multiscale physiological structural hierarchy, complex drug clearance, and zonal physiology from the cell to tissue level in long-term cultured liver-on-a-chip is demonstrated. These methods are promising for future applications in pharmacodynamics and personal medicine.
器官型培养的显著进展未能克服表达组织特异性功能和复杂性的挑战，特别是对于需要多功能和复杂生物过程的器官，如肝脏。原代肝细胞是功能器官型重建的理想生物构建块，但由于其在体外迅速丧失生理完整性而受到限制。在这里，材料科学中使用的格子生长概念被应用于开发一种组织培养箱，该培养箱提供生理线索并控制原代细胞的 3D 组装。这些线索包括生物生长模板、空间共培养、仿生径向流和无支架条件下的循环。从细胞到组织水平，长期培养的肝芯片中多尺度生理结构层次、复杂药物清除和区域生理的再现可行性得到了证明。这些方法有望在药效学和个性化医疗方面得到应用。
