Cardiac Microtissue Force System for Preclinical Drug Screening and Toxicity Asse

描述（由申请人提供）：Innolign Biomedical开发了一种新的微组织系统，用于评估潜在的药物心脏毒性，该系统使用的技术允许创建小型化的人体组织结构并测量其生物力学活性。这项I期SBIR提案的目标是建立使用这些被称为CardioMicroTug的工程3D人类心脏微组织微制造阵列的可行性，以一种新的高通量格式来评估药物的心脏毒性。心脏毒性在新药和生物制药开发中是一个重要的药物经济学问题，部分原因是目前的毒理学研究未能充分预测药物开发过程中潜在的心脏安全性问题。组织工程的最新进展表明，体外工程化的人心脏组织可以作为候选药物化合物的安全性评估平台。CardioMicroTug的特点是对齐心脏微组织锚定在微制造悬臂梁上。这些悬臂实时报告心脏微组织产生的力，从而提供人类心脏生物力学功能的直接读数。Aim 1的目标是在工程心脏微组织中证明一致和可重复的生理相关生物力学反应。Aim 2的研究将评估CardioMicroTug在使用一组已知心脏调节剂治疗时预测收缩性变化的能力。这些研究将为CardioMicroTug作为一种高通量体外3D心脏显微组织检测系统的进一步商业开发奠定基础，用于评估药物化合物的心脏毒性。

DESCRIPTION (provided by applicant): Innolign Biomedical has developed a novel microtissue system for assessing potential drug cardiotoxicities using technologies that allow for the creation of miniaturized human tissue constructs and the measurement their biomechanical activity. The goal of this Phase I SBIR proposal is to establish the feasibility of using these microfabricated arrays of engineered 3D human cardiac microtissues, termed CardioMicroTug, in a novel, high-throughput format for assessing cardiotoxicity of drugs. Cardiac toxicity represents a significant pharmaco-economic problem in the development of new drugs and biopharmaceuticals in part because current toxicological studies fail to fully predict potential cardiac safety issues during the drug development process. Recent advances in tissue engineering suggest that engineered human cardiac tissue ex vivo could be used as a safety assessment platform for candidate drug compounds. CardioMicroTug features aligned cardiac microtissues anchored to microfabricated cantilevers. These cantilevers report forces generated by the cardiac microtissues in real time, thereby providing a direct readout of human cardiac biomechanical function. The goals of Aim 1 are to demonstrate consistent and reproducible physiologically relevant biomechanical responses in engineered cardiac microtissues. Studies in Aim 2 will evaluate the capability of CardioMicroTug to predict changes in contractility when treated with a panel of known cardiac modulators. These studies will set the stage for further commercial development of CardioMicroTug as a high-throughput in vitro 3D cardiac microtissue assay system for assessing cardiotoxicities of pharmaceutical compounds.