Cardiac Microtissue Force System for Preclinical Drug Screening and Toxicity Asse

描述(申请人提供)：Innoolign 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，使用的技术允许创建微型人体组织结构并测量其生物力学活性。这项第一阶段SBIR建议的目标是确定以一种新颖的高通量格式使用这些被称为心脏微管的工程3D人体心脏微组织的微加工阵列来评估药物的心脏毒性的可行性。心脏毒性是新药和生物药物开发中的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完全预测药物开发过程中潜在的心脏安全问题。组织工程学的最新进展表明，体外培养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。心脏微管的特点是对齐的心脏微组织固定在微型制造的悬臂梁上。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。目标1的目标是在工程化心脏微组织中展示一致和可重复性的生理相关生物力学反应。在AIM 2上的研究将评估当使用一组已知的心脏调节剂治疗时，心脏微管预测收缩能力变化的能力。这些研究将为心脏微管的进一步商业化开发奠定基础，使其成为一种用于评估药物化合物心脏毒性的高通量体外三维心脏微组织测试系统。

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.