IN VITRO VASCULAR PERFUSION SYSTEM

体外血管灌注系统

• 批准号: 2867650
• 负责人: LAWRENCE A. BECK
• 金额: $ 9.95万
• 依托单位: TISSUE ENGINEERING SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 1999-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2867650
• 关键词: animal tissue; biomedical equipment development; blood vessels; cardiovascular system; drug screening /evaluation; fluid flow; light microscopy; morphology; perfusion; physiologic stressor; scanning electron microscopy; tissue /cell culture; transmission electron microscopy; vascular endothelium; vascular smooth muscle

Commercial opportunities exist in the cardiovascular drug, gene therapy, and device markets for a high-fidelity, predictive in vitro vascular model that can bridge the gap between high throughput screening and pre=clinical trials for cardiovascular drug discovery and gene therapy development. The goal of this proposal is to develop and validate design parameters for a unique vascular perfusion system to sustain intact vascular tissues for high fidelity in vitro modeling and testing. The system will provide an organ culture platform on which excised vascular tissue can be maintained under controlled in vitro conditions of shear stress and pulsatile pressure to generate results more predictive of in vivo responses. The Phase I study will be directed at designing a novel perfusion manifold system that allows for varied vessel sizes, is optimized for control and monitoring of desired flow (shear stress), pulse wave, and pH. Phase II will encompass optimization of system components including a variable pulse wave perfusion system and unitized nutrient and oxygenation flowpath with integral injection and non- invasive sampling. Appropriate sensor and feedback controls will be established to allow reproducibility, documentation, and quality assurance. PROPOSED COMMERCIAL APPLICATION: The vascular organ culture system will be commercialized for use as an in vitro tool for pre-clinical cardiovascular drug and gene therapy development as well as basic research. Example target applications include: cellular and molecular dysfunction in atherosclerosis, gene therapy vector development, and cardiovascular drug discovery.

在心血管药物、基因治疗和器械市场中存在高保真、预测性体外血管模型的商业机会，该模型可以弥合心血管药物发现和基因治疗开发的高通量筛选和临床前试验之间的差距。本提案的目标是开发和验证独特血管灌注系统的设计参数，以维持完整的血管组织，用于高保真度体外建模和测试。该系统将提供器官培养平台，在该平台上，切除的血管组织可以在剪切应力和脉动压力的受控体外条件下保持，以产生更能预测体内反应的结果。第一阶段研究将致力于设计一种新型灌注歧管系统，该系统允许不同的血管尺寸，并针对所需流量（剪切应力）、脉搏波和pH值的控制和监测进行了优化。第二阶段将包括系统组件的优化，包括可变脉搏波灌注系统和具有整体注射和非侵入性采样的单元化营养和氧合流路。将建立适当的传感器和反馈控制，以实现再现性、记录和质量保证。拟定商业应用：该血管器官培养系统将商业化，用作临床前心血管药物和基因治疗开发以及基础研究的体外工具。目标应用的例子包括：动脉粥样硬化中的细胞和分子功能障碍，基因治疗载体开发和心血管药物发现。