Development of an Artificial Pump-Lung for Respiratory Failure

描述（由申请人提供）：本提案的目标是结合生物医学学科的新方法，努力设计可穿戴人工泵肺（APL）。APL将满足成人急性和慢性肺衰竭患者的全部呼吸需求。这种复杂的设备与生物工程研究合作计划非常相关，因为它需要血泵和氧合器设计等相关但不同领域的专业知识；2)跨膜传质；3)流场与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)传感器与反馈控制；6)基于hfm的原型快速成型和制造；7)临床扎根的生物界面。这项工作将产生一种关键装置，就像20年前引入早期心室辅助装置治疗心力衰竭一样，为那些患有病态、急性和慢性肺部疾病的人提供一种新的治疗选择。就像心脏疾病的血泵一样，我们相信机械氧合将适应新兴的范例，作为长期使用的工具，或者更好地用于恢复和修复方案，包括组织工程和干细胞植入方案。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，设计和分析人工泵肺（APL）的功能和流场相关生物相容性。APL的功能将包括在20~75 mmHg的压力下以3 ~ 6升/分钟的泵血能力和在5升/分钟的血流量下250毫升/分钟的氧/二氧化碳转移能力。流场生物相容性优化，包括限制停滞，溶血，血小板活化和沉积将通过改进流道几何形状发展；2)利用甘油/水溶液验证计算预测的APL设计在循环回路中的流动特性，并利用新鲜绵羊血液和8小时体内动物实验评估APL在循环回路中的功能和流场生物相容性。3)通过修饰APL装置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。肝素结合的有效性和耐久性将与非肝素基血液相容表面涂层进行比较。研究了改性对抗等离子体中空纤维膜（PRHFM）气体传递的相对影响。4)进行慢性（30天）羊体内实验，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。

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.