Development of an Artificial Pump-Lung for Respiratory Failure

开发治疗呼吸衰竭的人工泵肺

• 批准号: 7417972
• 负责人: Bartley P GriffIth
• 金额: $ 68.73万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-07 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7417972
• 关键词: Acute; Adult; Ally; Animals; Biomedical Engineering; Blood; Blood flow; Carbon Dioxide; Cell membrane; Characteristics; Chronic; Compatible; Complex; Deposition; Development; Devices; Discipline; Effectiveness; Engraftment; Failure; Feedback; Fiber; Gases; Glycerol; Goals; Heart Diseases; Heart failure; Hemolysis; Heparin; Hour; In Vitro; Liquid substance; Lung; Mechanics; Membrane; Modeling; Modification; Object Attachment; Oxygen; Oxygenators; Plant Roots; Plasma; Platelet Activation; Polymers; Pump; Pump lung; Recovery; Relative (related person); Research; Research Personnel; Resistance; Respiratory Failure; Scheme; Stem cells; Surface; Thrombosis; Tissue Engineering; Work; artificial lung; base; biomaterial compatibility; blood pump; day; design; in vivo; instrument; multidisciplinary; novel strategies; novel therapeutics; pressure; programs; prototype; repaired; research study; respiratory; sensor; surface coating; ventricular assist device; water solution

DESCRIPTION (provided by applicant): The goal of this proposal is to combine biomedical disciplines in new approaches in an effort to design a wearable artificial pump lung (APL). The APL will provide total respiratory needs of adults with acute and chronic lung failure. This complex device relates ideally to the bioengineering research partnership initiative as it requires expertise in the allied but distinct fields of 1) blood pump and oxygenator design; 2) transmembrane mass transfer; 3) complex modeling of flow field and gas exchange; 4) nonthrombogenic coatings and their application to durable polymer-based hollow fiber membranes (HFM); 5) sensors and feedback control; 6) rapid prototyping and fabrication of HFM-based prototypes, and 7) clinically rooted biologic interface. This work should result in a keystone device that will, like the introduction of early ventricular assist devices for heart failure 20 years earlier begin a new therapeutic option for those with morbid, acute, and chronic pulmonary illnesses. Like blood pumps for heart disease, we believe that mechanical oxygenation will fit into emerging paradigms as instruments for chronic use or preferably for recovery and repair scenarios that include schemes of tissue engineering and stem cell engraftment. The specific aims of this proposal are: 1) To use computational fluid dynamics (CFD) based multidisciplinary modeling to design and analyze the function and flow field related biocompatibility of the artificial pump-lung (APL). The function of the APL will include its ability to pump blood at 3 ~ 6 liters/minute against pressure of 20~75 mmHg and oxygen/carbon dioxide transfer of 250 ml/min at a blood flow of 5 liters/minute. Flow field biocompatibility optimization that includes limitation of stasis, hemolysis, and platelet activation and deposition will be developed by refinement of flow path geometry; 2) To validate the computationally predicted flow characteristics of the APL design in a circulatory flow loop using glycerol/water solution and to evaluate the function and flow field biocompatibility of the APL in a circulatory loop using fresh ovine blood, and 8 hour in-vivo animal studies. 3) To reduce in-vitro and in-vivo platelet activation and thrombosis by modifying blood contacting polymer surfaces of the APL device. Effectiveness and durability of heparin bonding will be compared to non heparin-based blood compatible surface coatings. The relative effects of the modifications on gas transfer of plasma resistant hollow fiber membranes (PRHFM) will be determined. 4) To perform chronic (30 day) in-vivo ovine experiments to assess the long-term function, biocompatibility and durability of the APL device and its effect on the animal.

描述（由申请人提供）：该提案的目标是将生物医学学科与新方法相结合，努力设计可穿戴式人工泵肺（APL）。 APL 将为患有急性和慢性肺衰竭的成人提供全部呼吸需求。这种复杂的设备非常适合生物工程研究合作伙伴计划，因为它需要相关但不同领域的专业知识：1）血泵和氧合器设计； 2）跨膜传质； 3）流场和气体交换的复杂建模； 4）非血栓形成涂层及其在耐用聚合物基中空纤维膜（HFM）中的应用； 5）传感器和反馈控制； 6) 基于 HFM 的原型的快速原型设计和制造，以及 7) 植根于临床的生物接口。这项工作应该会产生一种关键设备，就像 20 年前引入用于心力衰竭的早期心室辅助设备一样，为患有病态、急性和慢性肺部疾病的患者提供一种新的治疗选择。就像心脏病的血泵一样，我们相信机械氧合将适合新兴的范式，作为长期使用的工具，或者最好用于恢复和修复方案，包括组织工程和干细胞移植方案。该提案的具体目标是： 1）使用基于计算流体动力学（CFD）的多学科建模来设计和分析人工泵肺（APL）的功能和流场相关的生物相容性。 APL的功能包括能够在20~75毫米汞柱的压力下以3~6升/分钟的速度泵送血液，以及在5升/分钟的血流量下以250毫升/分钟的速度输送氧气/二氧化碳。将通过细化流路几何形状来开发流场生物相容性优化，包括限制停滞、溶血以及血小板活化和沉积； 2) 使用甘油/水溶液验证 APL 设计在循环流动回路中计算预测的流动特性，并使用新鲜羊血和 8 小时体内动物研究评估 APL 在循环回路中的功能和流场生物相容性。 3) 通过修改 APL 装置的血液接触聚合物表面来减少体外和体内血小板活化和血栓形成。肝素粘合的有效性和耐久性将与非肝素基血液相容性表面涂层进行比较。将确定修改对抗等离子中空纤维膜（PRHFM）气体传输的相对影响。 4) 进行长期（30天）绵羊体内实验，以评估APL装置的长期功能、生物相容性和耐久性及其对动物的影响。