Development of a Total Artificial Lung

描述(由申请人提供)：肺移植非常成功，但在列入名单和致命的肺衰竭之间的短时间内，供者的可获得性受到限制。这一问题变得更加严重，因为许多潜在的肺捐赠者不被接受，因为在没有机械支持的情况下，临界性肺功能在术后可能被证明是致命的。体外生命支持(ECLS)可以在数周内替代肺功能，但不是移植的合适桥梁。可以工作3-6个月的可植入的全人工肺(TAL)将使更多的患者成功地接受肺移植，就像脑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，以开发临床TAL。我们获得了生物工程研究伙伴关系(BRP)的资助，通过原型阶段设计和测试可植入的全人工肺(TAL)。我们已经完成了那个项目的目标。具体地说，我们开发了用于TAL设计的脉动流装置气体交换和血流动力学的计算机模型。我们已经设计、制造和测试了器件，产生了符合功能TAL规格的原型(“Biolung”)。我们开发了一种伺服调节系统，通过调节扫气流量来控制二氧化碳的清除。我们常规地将TAL植入健康绵羊体内7天，使我们能够确定在临床试验之前必须解决的剩余问题。这些问题是潜在的空气栓塞、抗凝和血栓形成，决定理想的附着模式和TAL血流速度，以及在30天的应用中的耐用性。在BRP更新的支持下，我们现在提出解决这些问题，目标是在五年内进入临床试验。我们的研究外科医生、生物工程师和产业界团队已经完成了这个项目的前半部分，并准备完成它。密歇根大学的这个研究团队包括罗伯特·巴特利特医学博士，他是一名临床医生兼研究员，以ECMO和呼吸衰竭方面的工作而闻名；基思·库克博士，生物医学工程师，在全人工肺的开发方面有13年的经验；乔纳森·哈夫特医学博士，他是心脏外科医生，在人工肺测试和临床心脏和肺移植方面有经验；罗纳德·赫施尔医学博士，临床医生，在先进的呼吸支持技术方面有15年的研究经验。此外，MC3公司的Scott Merz博士是一名生物医学工程师，在人工肺和其他心肺设备的开发方面拥有16年的经验。

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.