Improving Cardiovascular Tissue Models Via Bio-Ionic Liquid Functionalized Hydrogels

Adverse reactions account for 30% of all drug discontinuations with cardiovascular toxicity as the most common complication¹. Because of this, current drug development projects span around 10-15 years and cost billions of dollars before approval from the Food and Drug Administration is granted². One major contributor to the unpredicted adverse effects of medications in the clinic is the physiological limitations of conventional preclinical models, primarily 2D cell cultures³. While these systems have been an industry standard, they display abnormal gene expression and morphology, resulting in poor simulation of native tissues³. In response, hydrogels (3D crosslinked networks of hydrophilic polymers) have gained interest as a preclinical screening platform because they can emulate the native extracellular matrix which improves biomimicry⁴. However, many polymers are non-conductive, which has presented complications for modeling excitable tissues like the heart^5,6. To improve the simulation of the cardiovascular system, the unique electrophysiological characteristics of myocardial tissue should be considered. This work explores the ability of a novel ionically conductive hydrogel to enhance the modeling of the myocardium. In this work, we employ material characterization to tune the biomaterial to cardiovascular mechanical properties. We then evaluate the signaling networks of the culture using a planar microelectrode array (MEA) which is a device composed of electrodes capable of recording extracellular electrophysiology. This research suggests that an 8% (w/v) Gelatin Methacryloyl (GelMA) + 3.5% (v/v) Choline Acrylate hydrogel, nicknamed Gel-Amin, can amplify signaling from a culture of cardiomyocytes (CMs; heart cells responsible for beating) to generate cultures with improved beating synchronicity compared to a GelMA control (Figure 1). The engineered 3D cell culture platform presents a cost-effective, high-throughput accessible device capable of integrating into drug development to better predict cardiotoxicity. By creating an improved model of the heart, this research seeks to decrease drug development costs and timelines, ultimately accelerating the availability of life-saving therapies to patients.

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