Development of a physiological cardiac microtissue platform for drug development

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Poor efficacy and unpredictable toxic effects of drugs on the heart are leading causes of**removal of a drug from the market. Many drugs act unpredictably in patients because they are**tested in labs using cells grown in plastic dishes and in animals that poorly mimic humans.**Improved heart tissue models could identify and eliminate toxic and ineffective drugs earlier in**the drug discovery process.**To meet this need, we have developed a microfluidic platform that can model features of**tissues in the body, like blood flow and three-dimensional tissue arrangement, better than can**be done with standard cell culture models. This platform will be adapted to stretch and**electrically stimulate heart microtissues to better simulate human heart physiology. We have**also developed a new ultrasound imaging technique that can rapidly assess heart microtissue**beating and contraction from outside the platform. We propose to combine these techniques**to develop a new and improved heart model to rapidly and easily assess the function of heart**microtissues. This model will be unique in its compatibility with standard laboratory equipment**and medium- to high-throughput workflow, ensuring ease of implementation with minimal time**and effort.**We will optimize the new heart model to achieve functionality more similar to native human**heart tissue than currently possible, using patient-derived heart cells to model normal and**diseased heart tissue. At project completion, we will deliver a new best-in-class model of**human heart tissue that is expected to decrease the time and cost associated with drug**development by identifying ineffective and toxic drugs much earlier in the drug development**process than is possible with current methods.**This project will produce technologies that are primed for commercialization by our partner**companies and trainees with interdisciplinary expertise to lead the next generation of**innovations in the Canadian biotechnology, biomedicine, and health sectors.