Microfabrication of liver and heart tissues for drug development

摘要

Drug-induced liver-and cardiotoxicity remain among the leading causes of preclinical and clinical drug attrition, marketplace drug withdrawals and black-box warnings on marketed drugs. Unfortunately, animal testing has proven to be insufficient for accurately predicting drug-induced liver-and cardiotoxicity across many drug classes, likely due to significant differences in tissue functions across species. Thus, the field of in vitro human tissue engineering has gained increasing importance over the last 10 years. Technologies such as protein micropatterning, microfluidics, three-dimensional scaffolds and bioprinting have revolutionized in vitro platforms as well as increased the long-term phenotypic stability of both primary cells and stem cell-derived differentiated cells. Here, we discuss advances in engineering approaches for constructing in vitro human liver and heart models with utility for drug development. Design features and validation data of representative models are presented to highlight major trends followed by the discussion of pending issues. Overall, bioengineered liver and heart models have significantly advanced our understanding of organ function and injury, which will prove useful for mitigating the risk of drug-induced organ toxicity to human patients, reducing animal usage for preclinical drug testing, aiding in the discovery of novel therapeutics against human diseases, and ultimately for applications in regenerative medicine.