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第一个真正便携式、生物相容性的、能够提供短期和长期呼吸支持的人工肺，改善患有急性和慢性肺部疾病的退伍军人的康复。目前的人工肺装置已显示出对肺部疾病康复的希望。然而，要充分发挥其潜力，需要在气体交换、生物相容性和便携性方面取得重大进展。当前的优点审查提案的目标是实现长期目标的一步，是充分表征微制造人工肺的离体气体交换特性和寿命，其特征尺寸和生理特性接近人肺，作为设计参数和生物相容性表面涂层的函数。因此，我们期望这项优点审查研究能够为将这种强大的技术转化为临床环境奠定基础。该项目的目标将通过三个目标来实现。第一个目标是建造血道高度小至10·5m、气体扩散膜薄至8·5m的人工肺，并用人体全血进行测试，以便首次评估小型化对气体交换效率的影响。由于我们的人工肺的微尺度特征尺寸，以及血栓形成限制装置性能的巨大潜力，第二个目标将研究具有已知可改善血液相容性并在体外测试功能化的合成或生物模式的PDMS基底的功能化。第三个目标将整合目标1中优化的设计参数和目标2中优化的抗血栓修饰，开发表面修饰的微机械人工肺原型，以改善血液相容性，减少血栓形成，并延长装置寿命。该原型将用人类全血进行离体测试。这些目标的完成将导致对微加工、血液相容性人工肺的性能极限进行表征，其特征尺寸和生理特性将首次接近人肺的特征尺寸和生理特性。在这项研究结束时，我们将能够通过将其应用于针对退伍军人肺康复的特定系统，将该技术转化为临床环境。