Development of an Artificial Pump-Lung for Respiratory Failure

描述(由申请人提供)：这项提案的目标是结合生物医学学科的新方法，努力设计一种可穿戴的人工泵肺(APL)。APL将为患有急性和慢性肺衰竭的成年人提供总的呼吸需求。这种复杂的设备非常适合生物工程研究伙伴计划，因为它需要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)非血栓涂层及其在耐用聚合物中空纤维膜(HFM)中的应用、5)传感器和反馈控制、6)基于HFM的原型的快速成型和制造以及7)临床植根生物界面等领域的专业知识。这项工作应该会产生一种Keystone设备，它将像20年前为心力衰竭引入早期心室辅助设备一样，为那些患有病态、急性和慢性肺部疾病的人开始一种新的治疗选择。就像心脏疾病的血泵一样，我们相信机械氧合将适合作为慢性使用的工具，或者更好地用于包括组织工程和干细胞植入方案的恢复和修复方案。该方案的具体目的是：1)利用基于计算流体力学(CFD)的多学科模型设计和分析人工泵-肺(APL)的功能和与流场相关的生物相容性。APL的功能将包括在20~75毫米汞柱的压力下以3~6升/分钟的速度泵血，以5升/分钟的血流量输送250毫升/分钟的氧气/二氧化碳。将通过改进流道几何形状来开发包括限制淤血、溶血和血小板激活和沉积在内的流场生物相容性优化；2)验证APL设计在使用甘油/水溶液的循环流环中的计算预测流动特性，并使用新鲜羊血进行APL在循环环路中的功能和流场生物兼容性评估，以及8小时的体内动物实验。3)通过对APL装置与血液接触的聚合物表面进行改性，减少体内和体外的血小板活化和血栓形成。肝素粘合的有效性和耐用性将与非肝素血液相容性表面涂层进行比较。测定了不同改性方法对中空纤维膜气体传递的相对影响。4)进行长期(30天)的绵羊体内实验，以评估APL装置的长期功能、生物相容性和耐用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.