Development of a Total Artificial Lung

描述（由申请人提供）：肺移植非常成功，但在上市和致命性肺衰竭之间的短暂窗口期间受到捐赠者可用性的限制。这个问题变得更加严重，因为许多潜在的肺捐献者不被接受，因为在没有机械支持的术后期间，临界肺功能可能会致命。体外生命支持 (ECLS) 可以替代肺功能数周，但并不是移植的适当桥梁。可以发挥3-6个月功能的植入式全人工肺（TAL）将使更多患者能够成功进行肺移植，就像心室辅助装置已应用于心力衰竭和移植一样。 2001 年，我们开始了一个为期十年的项目来开发临床 TAL。我们获得了生物工程研究合作伙伴 (BRP) 资助，用于设计和测试可植入全人工肺 (TAL) 的原型阶段。我们已经完成了该项目的目标。具体来说，我们开发了装置气体交换和脉动流血流动力学的计算机模型，以应用于 TAL 设计。我们设计、制造和测试了设备，产生了符合功能性 TAL 规格的原型（“Biolung”）。我们开发了伺服调节系统，通过调节吹扫气流量来控制二氧化碳清除。我们通常将 TAL 植入健康羊体内 7 天，以便我们在临床试验前找出必须解决的剩余问题。这些问题包括空气栓塞、抗凝和血栓形成的可能性，决定理想的附着方式和 TAL 血流速率，以及 30 天应用的耐久性。在BRP更新的支持下，我们现在建议解决这些问题，目标是在五年内进行临床试验。我们的研究外科医生、生物工程师和工业界团队已经完成了该项目的前半部分，并准备将其完成。这个来自密歇根大学的研究团队包括医学博士罗伯特·巴特利特 (Robert Bartlett)，他是一位临床医生兼研究员，因其在 ECMO 和呼吸衰竭方面的工作而闻名。 Keith Cook 博士，生物医学工程师，拥有 13 年全人工肺开发经验； Jonathan Haft，医学博士，心脏外科医生，在人工肺测试和临床心肺移植方面拥有丰富经验； Ronald Hirschl 医学博士是一名临床医生，在先进呼吸支持技术方面拥有 15 年的研究经验。此外，MC3, Inc. 的 Scott Merz 博士是一位生物医学工程师，在开发人工肺和其他心肺设备方面拥有 16 年经验。

DESCRIPTION (provided by applicant): Lung transplantation is very successful but limited by availability of donors during the short window between listing and fatal lung failure. This problem is worsened because many potential lung donors are not accepted as borderline lung function might prove fatal in the postoperative period without mechanical support. Extracorporeal Life Support (ECLS) can replace lung function for weeks but is not an appropriate bridge to transplantation. An implantable, total artificial lung (TAL) that could function for 3-6 months would allow more patients to undergo successful lung transplantation, just as the ventricular assist device has been applied to cardiac failure and transplantation. In 2001, we began a ten year project to develop a clinical TAL. We were awarded a bioengineering research partnership (BRP) grant to design and test an implantable total artificial lung (TAL) through the prototype stage. We have completed the goals of that project. Specifically we have developed computer models of device gas exchange and hemodynamics with pulsatile flow to apply to TAL design. We have designed, fabricated, and tested devices, resulting in a prototype (the "Biolung") which meets the specifications for a functional TAL. We developed a servoregulation system to control CO2 clearance by regulating the sweep gas flow. We have routinely implanted the TAL into healthy sheep for 7 days, allowing us to identify the remaining problems which must be solved before clinical trials. These problems are the potential for air embolism, anticoagulation and thrombosis, determining the ideal mode of attachment and TAL blood flow rate, and durability in a 30 day application. With support from renewal of the BRP, we now propose to solve those problems, with the goal of proceeding to clinical trials in five years. Our team of research surgeons, bioengineers, and industry has completed the first half of this project and is ready to bring it to completion. This research team from the University of Michigan includes Robert Bartlett, M.D., a clinician-researcher renowned for his work in ECMO and respiratory failure; Keith Cook, Ph.D., a biomedical engineer with 13 years of experience in the development of total artificial lungs; Jonathan Haft, M.D., a cardiac surgeon with experience in artificial lung testing and clinical heart and lung transplantation; and Ronald Hirschl, M.D., a clinician with 15 years of investigative experience in advanced respiratory support techniques. In addition, Scott Merz, Ph.D., of MC3, Inc., is a biomedical engineer with 16 years experience in the developing artificial lungs and other cardiopulmonary devices.