Ex vivo characterization of a microfabricated artificial lung

微型人工肺的离体表征

• 批准号: 8466807
• 负责人: Joseph Allen Potkay
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466807
• 关键词: Acute; Adhesions; Adsorption; Affect; Albumins; Biocompatible; Biocompatible Materials; Biological; Blood; Blood Platelets; Blood Proteins; Carbon Dioxide; Chemicals; Chromium; Chronic; Chronic Obstructive Airway Disease; Chronic lung disease; Clinical; Construction Materials; Development; Devices; Diagnosis; Diffusion; Disease; Dust; Edetic Acid; Endothelial Cells; Fibrinogen; Foundations; Freedom; Gases; Goals; Gulf War; Healthcare Systems; Height; Heparin; Human; In Vitro; Investigation; Laboratories; Length; Ligands; Lung; Lung diseases; Membrane; Methods; Metric; Miniaturization; Modality; Modification; Oxygen; Paint; Peptides; Performance; Permeability; Physiological; Polyethylene Glycols; Polymers; Population; Positioning Attribute; Property; Rehabilitation therapy; Reporting; Resistance; Respiratory System; Services; Silicones; Surface; Surveys; System; Technology; Testing; Theoretical model; Thick; Thrombosis; Time; Translating; Translations; Veterans; Whole Blood; Width; abstracting; artificial lung; base; biomaterial compatibility; design; disability; experience; improved; interfacial; macromolecule; operation; portability; prototype; pulmonary rehabilitation; respiratory; surface coating; technology development

DESCRIPTION (provided by applicant): Project Summary/Abstract The long-term goal of this technology development project is improve the rehabilitation of veterans suffering from acute and chronic lung diseases through the development of the first truly portable, biocompatible artificial lung capable of short and long term respiratory support. Current artificial lung devices have shown promise for rehabilitation from lung disease; however, significant advances in gas exchange, biocompatibility, and portability are required to fully realize their potential. The objective of the current Merit Review proposal, which is a step toward attainment of the long-term goal, is to fully characterize the ex vivo gas exchange properties and lifetimes of microfabricated artificial lungs with feature sizes and physiological properties approaching that of the human lung as a function of design parameters and biocompatible surface coatings. Thus, we expect this Merit Review study to provide the foundation for translation of this robust technology to the clinical setting. The project objectives will be achieved in three aims. In the first aim, artificial lungs with blood channel heights as small as 10 5m and gas diffusion membranes as thin as 8 5m will be constructed and tested with human whole blood in order to, for the first time, evaluate the impact of miniaturization on gas exchange efficiencies. Due to the microscale feature size of our artificial lung, and the significant potential for thrombogenesis limiting device performance, the second aim will investigate functionalization of PDMS substrates with synthetic or biological modalities that are known to improve hemocompatibility and test the functionalizations in vitro. In the third aim, the design parameters optimized in Aim 1 and the thromboresistant modification optimized in Aim 2 will be integrated to develop a surface-modified micromachined artificial lung prototype in order to improve hemocompatibility, reduce thrombosis, and increase device lifetime. The prototype will be tested ex vivo with human whole blood. The completion of these aims will result in the characterization of the performance limits of microfabricated, hemocompatible, artificial lungs with feature sizes and physiological properties that are, for the first time, approaching those in the human lung. At the conclusion of this study, we will be well positioned to translate the technology to the clinical setting through its application in specific systems targeted at veteran pulmonary rehabilitation.

描述（由申请人提供）： 项目摘要/摘要该技术开发项目的长期目标是通过开发能够短期和长期呼吸支持的第一个真正便携式，生物相容性的人工肺来改善患有急性和慢性肺部疾病的退伍军人的康复。当前的人工肺设备显示出有望从肺部疾病中康复。但是，需要大量的天然气交换，生物相容性和可移植性，以充分发挥其潜力。当前的优异审查提案的目的是实现长期目标的一步，是充分表征具有特征大小和生理特性的微型人工肺的离体气体交换特性和寿命，该特性接近人类肺部的目的是设计参数和生物兼容表面涂层的函数。因此，我们希望这项优异审查研究为将这种强大技术转换为临床环境提供了基础。项目目标将在三个目标中实现。在第一个目标中，将构造并用人类全血构建和测试的血通道高至10 5M的人造肺，而气体扩散膜将首次构建和测试，以评估微型化对气体交换效率的影响。由于我们人造肺的显微镜特征大小以及限制器件性能的显着潜力，第二个目标将研究具有合成或生物学方式的PDMS底物的功能化，这些底物已知可以改善血液相容性并在体外测试功能。在第三个目标中，在AIM 1中优化的设计参数和AIM 2中优化的动力抗性修饰将集成以开发表面修饰的微机械人工肺原型，以提高血栓形成，减少血栓形成并增加设备寿命。该原型将用人类全血离体测试。这些目的的完成将导致表征微生物，血液相容的，人造肺的性能限制，具有特征大小和生理特性，这是第一次接近人类肺中的肺部。在这项研究的结论中，我们将通过其在针对退伍军人肺部康复的特定系统中的应用将技术转化为临床环境。