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Ultra?compliant Indwelling Elastomer Balloons Improve Stability and Performance of Bioengineered Human Mini?Hearts

Animal models used by the pharmaceutical industry to define drug safety and efficacy are expensive, resource?intensive, subject to interspecies differences, and often fail to predict human responses. Therefore, engineered human tissue preparations are gaining importance as in vitro models to address translation from preclinical data to clinical outcome. Methods that improve fabrication consistency, usability, and physiological relevance of tissues are crucial. For cardiac applications, the goal is to form a miniature 3D?chamber that mimics physiology and biomechanical properties of the ventricle, allowing measurement of clinically relevant endpoints such as pressure?volume relationships which cannot be obtained with simpler constructs. Despite advances in biofabrication, a perfusable mini?ventricle with a competent endocardium remains an unmet challenge, resulting in thin?walled organoids that are fluid permeable. We developed and validated a novel method for improving stability and performance of our human mini?heart model by creating an ultra?compliant elastomer balloon for hollow?organ engineering applications. Balloon properties, tissue formation, and biological data were examined. Findings demonstrate a thin permanent lining that is retained during testing and permits tissue contraction, eliminates leakage, increases uniformity, and enables multi?day longitudinal measurements. Biological data presented here shows reduced variability across measured cardiac parameters when compared to our previously published fabrication method.This article is protected by copyright. All rights reserved.

Publication date: 02/02/2022

Author: Erin Glenn Roberts, Suet Yee Mak, Andy On-Tik Wong, David D. Tran, Eugene K. Lee, Yosuke K. Kurokawa, Deborah K. Lieu, Roger J. Hajjar, Kevin D. Costa, Ronald A. Li

Advanced Engineering Materials

      

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 870292.