Cardiopulmonary Organ Engineering

心肺器官工程

• 批准号: 6913498
• 负责人: WILLIAM R WAGNER
• 金额: $ 96.99万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6913498
• 关键词: biomaterial development /preparation; biomaterial evaluation; biomechanics; blood vessel prosthesis; cell differentiation; clinical research; confocal scanning microscopy; cow; elastomers; electron microscopy; human subject; immunocytochemistry; laboratory rat; medical implant science; myocardial ischemia /hypoxia; myocardium; respirators; stem cells; swine; tissue engineering; total artificial organ

DESCRIPTION (provided by applicant): The aim of this proposal is to design solutions for vascular, cardiac, and pulmonary organ failure by building interactive teams of researchers focused on specific aspects of cardiopulmonary organ engineering. Our efforts will encompass three projects: a tissue engineered blood vessel, a myocardial patch, and a biohybrid lung. The assembled research teams will function as cores of expertise that address common tasks associated with all three projects. Five research cores will be established in the following areas: 1) matrix synthesis and surface modification, 2) precursor cell isolation and characterization, 3) biomechanical testing and conditioning, 4) animal model development, and 5) construct assessment. For each of the three organ projects we have design objectives (Specific Aims) that will be achieved in the five-year period of proposed work: 1) Tissue engineered blood vessel - A biological blood vessel will be developed that achieves long-term potency in the rat model and is subsequently evaluated in the porcine model. The blood vessel will be a "biological equivalent" to autologous arteries from a mechanical and biofunctional perspective. During vessel development in vitro, specific mechanical training protocols that have been optimized to direct appropriate cell differentiation and expression of matrix components will be employed. 2) Myocardial patch - A process will be developed that allows the reconstruction of functional myocardium in ischemic or dysfunctional regions of the heart, This process will be characterized by the seeding of stem cells onto a bioerodible thermoplastic elastomer which has been designed to micromechanically transmit appropriate stresses to the stem cells during an in vitro seeding period and after placement within the diseased myocardium. Vascularization of this implanted construct will be achieved by surgical placement of omental tissue atop the placed myocardial patch. 3) Biohybrid lung - An oxygenator comprised of endothelialized microporous hollow fibers arranged in: plates and rotated to mix and pump the blood will serve as a biohyrid lung capable of providing gas exchange in a calf for 14 days. The hollow fibers will be surface modified to support the culture of autologous endothelial cells. The endothelial cells will act to reduce the anticoagulation requirements of the device while maintaining adequate fiber permeability.

描述（由申请人提供）：该提案的目的是通过建立针对心肺器官工程特定方面的研究人员的交互式研究团队来设计血管，心脏和肺部器官故障的解决方案。我们的努力将包括三个项目：组织工程血管，心肌斑块和生物杂化肺。组装的研究团队将充当专业知识的核心，以解决与所有三个项目相关的常见任务。将在以下区域中建立五个研究核心：1）基质合成和表面修饰，2）前体细胞分离和表征，3）生物力学测试和调节，4）动物模型开发，以及5）构造评估。对于三个器官项目中的每个项目，我们都有设计目标（特定目的），这些目标将在拟议的五年内实现：1）组织工程血管 - 将开发出生物血管，以实现长期的效力大鼠模型并随后在猪模型中评估。从机械和生物功能的角度来看，血管将是自体动脉的“生物学上”。在体外血管发育过程中，将采用已优化的特定机械训练方案，以指导基质组件的适当细胞分化和表达。 2）心肌斑 - 将开发一个过程，该过程允许在心脏的缺血性或功能失调区域重建功能性心肌，该过程的特征是干细胞的播种是在可生物适用的热塑性弹性体上的播种，该弹性剂旨在微机械旨在微机械传输适当的微机械传输在体外播种期间和在患病的心肌内放置后，对干细胞的压力。该植入构建体的血管形成将通过在放置的心肌斑块上的手术放置在手术上来实现。 3）生物杂化肺 - 一种充氧剂，由内皮化的微孔空心纤维组成：板和旋转以混合和泵送血液的氧化剂将作为能够在小牛中提供气体交换14天的生物hyriD肺。空心纤维将进行表面修饰，以支持自体内皮细胞的培养。内皮细胞将采取行动减少设备的抗凝要求，同时保持足够的纤维渗透性。