Development of high-throughput cardiotoxicity and hepatotoxicity assays with magnetic 3D bioprinting

PROJECT SUMMARYThe goal of this proposal is to develop assays for cardiotoxicity and hepatotoxicity using magneticD bioprintingBoth cardiotoxicity and hepatotoxicity are critical areas for safety testingand in need of more accurate in vitro screens to prevent costly market withdrawalsHowevercurrent in vitro options are lacking in throughput and representation of native tissue environmentsThis proposal uses magneticD bioprinting to createD in vitro culture models that mimic native tissueThe principle behind magneticD bioprinting is the magnetization of cells and their printing using magnetic forcesThis method is rapid and easy to useand escapes the technical issue of otherD culture models that limit its use for high throughput screeningIn Phase Ia general toxicity assaythe BiO Assaywas developed using magneticallyD bioprinted spheroidsThis Phase II builds on that successby developing this cytotoxic assay for cardiomyocytes and hepatocytesthen further developing tissue specific functional assays to determine the effect of compounds on tissue functionFor cardiomyocytesa beating assay will be developed to assay a compound s effect on beatingwhile for hepatocytesan assay for cytochrome Pinduction inhibition will be developed to assay a compound s effect on metabolismIn combination with other assayssuch as LC MS and fluorescent calcium signaling assaysour assays will offer high content and high throughput solutions to study both cytotoxicity and functional toxicityThis work aids NIEHS in its goal of finding in vitro solutions for toxicity screening that are high throughput and representative of native tissue environmentsThe end result of this proposed work is a full suite of assays to study a compound s cardiotoxic and hepatotoxic effects