Ex vivo characterization of a microfabricated artificial lung

微型人工肺的离体表征

• 批准号: 8088739
• 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/8088739
• 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; 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. PUBLIC HEALTH RELEVANCE: Chronic obstructive pulmonary disease (COPD) affects approximately 16% of the veteran population. COPD is now the fourth most prevalent disease in the VA population and one of the most costly to the VA health care system. Over 500,000 service-connected respiratory disabilities have been diagnosed in veterans and 6.5% of all Gulf War service-connected disabilities are respiratory system related. Operation Enduring Freedom and Operation Iraqi Freedom Veterans have been exposed to chemicals known to cause acute and chronic respiratory conditions including CARC paint and chromium dust. Over 2.3 million veterans reported having some form of "lung trouble" in the 2001 National Survey of Veterans. This project has the potential to revolutionize the rehabilitation of veterans suffering from acute and chronic lung diseases through the development of a truly portable, biocompatible, artificial lung capable of short and long term respiratory support.

描述（由申请人提供）： 项目概要/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、生物相容性人工肺，能够进行短期和长期呼吸支持，改善患有急性和慢性肺部疾病的退伍军人的康复。目前的人工肺设备已显示出从肺部疾病康复的希望;然而，需要在气体交换，生物相容性和便携性方面取得重大进展，以充分发挥其潜力。当前Merit审查提案的目的是实现长期目标的一个步骤，其目的是充分表征微制造人工肺的离体气体交换性能和寿命，其特征尺寸和生理特性接近人类肺，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Merit审查研究为将这种稳健的技术转化为临床环境提供基础。该项目的目标将在三个方面实现。在第一个目标，人工肺的血液通道高度小至10 5 m和气体扩散膜薄至8 5 m，将构建和测试与人类全血，以首次，评估小型化的影响，对气体交换效率。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显著潜力，第二个目标将研究具有已知可改善血液相容性的合成或生物形式的PDMS基底的功能化，并在体外测试功能化。在第三个目标中，目标1中优化的设计参数和目标2中优化的抗血栓改性将被集成以开发表面改性的微机械人工肺原型，以改善血液相容性，减少血栓形成，并增加设备寿命。原型将使用人全血进行离体测试。这些目标的完成将导致表征的性能极限的微制造，血液相容性，人工肺的特征尺寸和生理特性，是第一次，接近那些在人类肺部。在这项研究的结论，我们将很好地定位，通过其在针对退伍军人肺康复的特定系统中的应用，将该技术转化为临床环境。 公共卫生关系： 慢性阻塞性肺疾病（COPD）影响了大约16%的退伍军人。COPD现在是退伍军人管理局人口中第四常见的疾病，也是退伍军人管理局医疗保健系统成本最高的疾病之一。在退伍军人中诊断出超过50万例与服务有关的呼吸系统残疾，6.5%的海湾战争与服务有关的残疾与呼吸系统有关。持久自由行动和伊拉克自由行动退伍军人暴露于已知会引起急性和慢性呼吸道疾病的化学品，包括CARC油漆和铬尘。在2001年全国退伍军人调查中，超过230万退伍军人报告患有某种形式的“肺病”。该项目有可能通过开发一种真正便携、生物相容、能够提供短期和长期呼吸支持的人工肺，彻底改变患有急性和慢性肺部疾病的退伍军人的康复。