Collaborative Research: Transforming Cardiotoxic Drug Screening Using Bioprinted Myocardial Tissue Model with Self-Sensing Capacity

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Cardiotoxicity represents a major segment of drug toxicities, so there are considerable concerns about the cardiovascular safety profile of drugs used for non-cardiovascular medication. Conventional drug screening approaches, such as using a 2-dimensional cell culture and animal models, have notable limitations. Approaches are needed to fabricate cardiac tissue models that more reliably reproduce human physiology with respect to their structure and function. For cardiotoxicity assays it is equally important to monitor the behavior of the model tissue in response to drugs, ideally in a label-free and non-invasive manner. The goal of this research project is to develop an engineered cardiac tissue model for cardiotoxicity screening that will facilitate drug screening and personalized medicine. The design of the 3-dimensional model involves cardiac tissues that are embedded with soft and stretchable microelectronics that can continuously measure cardiotoxicity within the tissue. The outcomes of this project could lead to significant cost reductions for drug development by accurately predicting human responses to drug candidates. The research also could help reduce the use of animal models for drug screening. The project will provide opportunities to promote STEM education for K-12 students, especially those from under-represented groups, and to disseminate science and engineering knowledge to the public.This research project aims to develop a multi-material, stereolithographically-bioprinted cardiac tissue model with embedded soft and stretchable microelectronics. The main research idea is that seamless integration of mechanically matched soft microelectronics and bioprinted cardiac models will allow for continuous, in situ and intra-tissue measurements of cardiotoxicity in real time and in response to pharmaceutical compounds. The project participants will conduct experimental and analytical studies to design, optimize, fabricate, characterize and validate the hybridized cardiac tissue model. Specific steps include 1) optimizing the design and fabrication of the engineered microvascularized cardiac tissue model to achieve structural and functional similarity to its in vivo counterpart, 2) designing, analyzing, fabricating, and testing soft, stretchable microelectronics, 3) integrating the soft microelectronics with the bioprinted cardiac tissue to form hybridized cardiac tissue model, and 4) studying the screening of a panel of drugs with induced electrophysiological and mechanical beating signals from the intra-tissue microelectronics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.