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: 7668120
• 负责人: Bartley P GriffIth
• 金额: $ 7.5万
• 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/7668120
• 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）：本提案的目标是在新方法中结合联合收割机生物医学学科，以设计可穿戴式人工泵肺（APL）。APL将提供急性和慢性肺衰竭成人的全部呼吸需求。这种复杂的装置理想地与生物工程研究伙伴关系倡议有关，因为它需要以下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）上的应用; 5）传感器和反馈控制; 6）基于HFM的原型的快速原型和制造，和7）临床上扎根的生物界面。这项工作应该会产生一个关键的设备，就像20年前引入早期心室辅助设备治疗心力衰竭一样，开始为那些患有病态，急性和慢性肺部疾病的人提供新的治疗选择。就像心脏病的血泵一样，我们相信机械氧合将适合作为长期使用的工具或优选用于恢复和修复方案的新兴范例，包括组织工程和干细胞移植方案。本课题的具体目标是：1）利用基于计算流体力学（CFD）的多学科建模方法，对人工泵肺（APL）的功能和流场相关生物相容性进行设计和分析。APL的功能将包括其在20~75 mmHg压力下以3 ~ 6升/分钟泵送血液的能力，以及在5升/分钟血流下以250 ml/分钟输送氧气/二氧化碳的能力。将通过改进流路几何形状来优化流场生物相容性，包括限制停滞、溶血和血小板活化和沉积; 2）验证APL设计在使用甘油/水溶液的循环流动回路中的计算预测的流动特性，并评估APL在使用新鲜绵羊血的循环回路中的功能和流场生物相容性，和8小时体内动物研究。3)通过修饰APL器械的血液接触聚合物表面，减少体外和体内血小板活化和血栓形成。将肝素粘合的有效性和耐久性与非肝素基血液相容性表面涂层进行比较。将确定改性对耐等离子体中空纤维膜（PRHFM）的气体传递的相对影响。4)进行长期（30天）绵羊体内实验，以评估APL器械的长期功能、生物相容性和耐久性及其对动物的影响。