Step-by-step fabrication of heart-on-chip systems as models for cardiac disease modeling and drug screening

Cardiovascular diseases are caused by hereditary factors, environmental conditions, and medication-related issues. On the other hand, the cardiotoxicity of drugs should be thoroughly examined before entering the market. In this regard, heart-on-chip (HOC) systems have been developed as a more efficient and cost-effective solution than traditional methods, such as 2D cell culture and animal models. HOCs must replicate the biology, physiology, and pathology of human heart tissue to be considered a reliable platform for heart disease modeling and drug testing. Therefore, many efforts have been made to find the best methods to fabricate different parts of HOCs and to improve the bio-mimicry of the systems in the last decade. Beating HOCs with different platforms have been developed and techniques, such as fabricating pumpless HOCs, have been used to make HOCs more user-friendly systems. Recent HOC platforms have the ability to simultaneously induce and record electrophysiological stimuli. Additionally, systems including both heart and cancer tissue have been developed to investigate tissue-tissue interactions' effect on cardiac tissue response to cancer drugs. In this review, all steps needed to be considered to fabricate a HOC were introduced, including the choice of cellular resources, biomaterials, fabrication techniques, biomarkers, and corresponding biosensors. Moreover, the current HOCs used for modeling cardiac diseases and testing the drugs are discussed. We finally introduced some suggestions for fabricating relatively more user-friendly HOCs and facilitating the commercialization process.