文献类型：期刊文献

英文题名：A three-dimensional (3D) liver-kidney on a chip with a biomimicking circulating system for drug safety evaluation

作者：Huang, Qihong[1];Yang, Tianhao[1];Song, Yunpeng[2];Sun, Wenxuan[1];Xu, Jian[2];Cheng, Ya[2];Yin, Ruixue[1];Zhu, Lili[3];Zhang, Mengting[3];Ma, Lei[3];Li, Honglin[3];Zhang, Hongbo[1]

机构：[1]East China Univ Sci & Technol, Sch Mech & Power Engn, Shanghai 200237, Peoples R China;[2]East China Normal Univ, Sch Phys & Elect Sci, Shanghai 200062, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2024

卷号：24

期号：6

起止页码：1715

外文期刊名：LAB ON A CHIP

收录：;EI(收录号：20240715562034);WOS:【SCI-EXPANDED(收录号:WOS:001157198600001)】；

基金：The authors would like to thank "The Shanghai Municipal Science and Technology Major Project" for the financial support.

语种：英文

外文关键词：Animals - Cell culture - Drug products - Etching - Metabolism - Metabolites - Ultrafast lasers

摘要：The liver and kidney are the major detoxifying organs in the human body and play an important role in pharmacokinetics. Drug-induced hepatotoxicity and nephrotoxicity can cause irreversible damage to the liver and kidney and are a major cause of drug failure in later stages. Both animal models and conventional cell culture have a number of limitations, such as animal ethics and gene mismatching and there is an urgent need to develop a new drug toxicity evaluation approach. In this paper, a 3D liver-kidney on a chip with a biomimicking circulating system (LKOCBCS) was constructed to obtain kidney and liver models in vitro for drug safety evaluation. LKOCBCS, which has a parallel circulating system mimicking biological circulation, consists of 3D biomimetic tissue of liver lobules similar to that of the human liver constructed by 3D bioprinting and renal proximal tubule barriers fabricated by ultrafast laser assisted etching. The proposed LKOCBCS facilitates the communication between the liver and the kidney, including the exchange of nutrients, compounds, and metabolites. The results revealed that the glucose concentration and cell metabolism stabilized after 7 days. A dynamically repeated low-dose administration of cyclosporine A (CsA) was fed to the system, and hepatotoxicity and nephrotoxicity were observed on day 3 according to the changes in toxicity markers. The high levels of drug induced biomarkers expressed in LKOCBCS indicate that this system is more sensitive than the monoculture liver chip and it is highly potential in replacing animal models for effective drug toxicity screening. A 3D liver-kidney on a chip with a biomimicking circulating system (LKOCBCS) was constructed to obtain kidney and liver models in vitro for drug safety evaluation.