Cardiac Microtissue Force System for Preclinical Drug Screening and Toxicity Asse

用于临床前药物筛选和毒性评估的心脏微组织力系统

• 批准号: 8590318
• 负责人: Michael Yang
• 金额: $ 19.64万
• 依托单位: INNOLIGN BIOMEDICAL, LLC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8590318
• 关键词: Achievement; Address; Adjuvant; Animals; Benchmarking; Biological Assay; Biological Products; Biomechanics; Cardiac; Cardiac Myocytes; Cardiotoxicity; Cells; Clinical; Data; Development; Devices; Drug Compounding; Drug Evaluation; Drug Industry; Drug Interactions; Drug toxicity; Economics; Electric Stimulation; Engineering; Feasibility Studies; Frequencies; Future; Goals; Heart; Human; Human Engineering; In Vitro; Industry; Measurement; Measures; Mechanical Stimulation; Metric; Microfabrication; Modeling; Neonatal; Organ; Output; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physiological; Pilot Projects; Preclinical Drug Evaluation; Predictive Value; Process; Rattus; Reporting; Reproducibility; Rest; Safety; Small Business Innovation Research Grant; Source; Staging; Stimulus; System; Techniques; Technology; Testing; Time; Tissue Engineering; Tissues; Toxicology; Ventricular; Work; base; cantilever; cell type; chronotropic; cost; cost effective; design; drug candidate; drug development; human embryonic stem cell; human tissue; improved; in vitro testing; in vivo; induced pluripotent stem cell; innovation; interest; meetings; mimetics; miniaturize; novel; pre-clinical; public health relevance; research and development; response; success

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.

描述（由申请人提供）：Innolign Biomedical开发了一种新型微组织系统，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I期SBIR提案的目标是建立使用这些工程化3D人类心脏微组织的微制造阵列的可行性，这些微制造阵列被称为MicroTug，以一种新型的高通量形式评估药物的心脏毒性。心脏毒性代表了新药和生物制药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性问题。组织工程的最新进展表明，离体工程化的人类心脏组织可用作候选药物化合物的安全性评估平台。MicroTug的特点是将对齐的心脏微组织锚定在微制造的杠杆上。这些杠杆报告由心脏微组织在真实的时间内产生的力，从而提供人类心脏生物力学功能的直接读数。目的1的目标是证明一致的和可重复的生理相关的生物力学反应，在工程化的心脏微组织。目标2中的研究将评价当使用一组已知心脏调节剂治疗时，EST-MicroTug预测收缩性变化的能力。这些研究将为MicroTug的进一步商业化开发奠定基础，MicroTug是一种高通量的体外3D心脏微组织测定系统，用于评估药物化合物的心脏毒性。