CTScreen: A 3D-Engineered Cardiac Tissue System for Automated Perfusion, Stimulation and Contractility Measurement

Medera Biopharmaceutical (Medera) was founded and is led by world pioneers and visionaries in gene therapy, cell therapy and precision medicine. Medera’s areas of focus are incurable human conditions with unmet needs, from common (heart failure, cancer) to rare (e.g., Duchenne Muscular Dystrophy, Friedreich Ataxia) diseases. Medera’s fully integrated pipeline uniquely and comprehensively covers (1) cell & gene therapies, (2) drug discovery and (3) current Good Manufacturing Practice (cGMP) compliant manufacturing of next-generation cell & gene therapeutics. Novoheart Limited is one of three companies under Medera and focuses on engineered cardiac tissues for drug discovery.

The CTScreen is Novoheart’s newest commercial platform that measures true contractility of 3D-engineered cardiac tissue under physiological conditions. The system allows quantitative assessment of the contractile response of healthy and diseased tissues, as required to study drug toxicity and efficacy. It also allows for tissue fabrication and functional characterization with minimal handling by the user, yielding high-content measurements of twitch force without complicated instrumentation.

Biomimetic 3D cardiac tissues with integrated force-sensitive end-posts can be constructed from stem cell-derived or primary cardiomyocytes using the custom elastomer cassettes provided. The tissue cassette can then be installed and analysed on the CTScreen setup, which comes complete with solenoid valve-controlled perfusion from 8 different channels, physiological temperature control, programmable electrical field stimulation, and real-time force readout derived from end-post detections during tissue contraction and relaxation. The system is compatible with our standard-sized human ventricular cardiac tissue strips, or hvCTS (~10mm length) in single-, double-, or triple-tissue formats, as well as arrays of hvCTS micro-tissues (~1.5mm length) for higher-throughput screening applications.

The CTScreen comes with fully-integrated acquisition and analysis software. The acquisition interface offers the ability to program test protocols for study automation, with real-time data readout for quick monitoring of functional responses. After acquisition, data can be merged from multiple experiments into a query-able table for quick analysis of 16 contractility-related parameters. This is a turn-key all-in-one system for assessment of cardiac muscle contractility and relaxation properties.

The CTScreen design is based on a system that Novoheart has been developing in-house for years, with extensively published validation studies, and we are excited to make it available for use by other laboratories. In this Xtalks webinar presentation, we will discuss the development of the CTScreen system’s unique features such as the glass perfusion chamber, multi-tissue bioreactors for running several tissues in parallel, automated protocol table, and user-friendly software. We will also present sample data collected using the system, and ongoing efforts to increase throughput and expand capabilities for users interested in myocardial physiology, disease modelling, cardiotoxicity, and drug discovery and development.

Speakers

Dr. Kevin Costa, CSO and Co-Founder, Novoheart

Prof. Costa is one of the scientific co-founders of Novoheart and has served as the CSO since 2017. He is Director of Cardiovascular Cell and Tissue Engineering at the Icahn School of Medicine at Mount Sinai in New York City, and was previously trained at the Johns Hopkins University and on the faculty as Associate Professor of Biomedical Engineering at Columbia University. As a “blue-blood” biomedical engineering (BME) expert (B.S. and M.S. in BME from Boston University, Ph.D. in BME from UC San Diego, and postdocs in BME from JHU and Washington University) in cell and tissue biomechanics and cardiac tissue engineering, he has developed one of the first engineered cardiac tissue systems and is an inventor of several cardiac tissue engineering technologies. Since 2009, he has been working with Prof. Ronald Li to translate such systems into human cells. Prof. Costa has received research funding from the Whitaker Foundation, the National Science Foundation (NSF) and the National Institutes of Health (NIH; NHLBI, NIBIB, and NIGMS). He was also a recipient of the prestigious Faculty Early Career Development (CAREER) Award from the NSF.

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Dr. Erin Roberts, Team Head of Biomedical Engineering, Novoheart

Dr. Erin Roberts is the head of the biomedical engineering team at Novoheart, having joined the company in 2018. She completed her PhD at Boston University in Materials Science and Engineering where, as part of her research, she designed and fabricated bio-MEMS for the stimulation and characterization of engineered cardiac tissue sheets in collaboration with Boston Children’s Hospital. She has an MS in Mechanical Engineering from The Georgia Institute of Technology and a BS in Chemical Engineering from Cornell University.

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