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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL069420-10
Application #
8088153
Study Section
Special Emphasis Panel (ZRG1-RES-D (52))
Program Officer
Harabin, Andrea L
Project Start
2002-02-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2011
Total Cost
$997,603
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Surgery
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Major, Terry C; Handa, Hitesh; Brisbois, Elizabeth J et al. (2013) The mediation of platelet quiescence by NO-releasing polymers via cGMP-induced serine 239 phosphorylation of vasodilator-stimulated phosphoprotein. Biomaterials 34:8086-96
Handa, Hitesh; Brisbois, Elizabeth J; Major, Terry C et al. (2013) In vitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-oped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive. J Mater Chem B Mater Biol Med 1:3578-3587
Brisbois, Elizabeth J; Handa, Hitesh; Major, Terry C et al. (2013) Long-term nitric oxide release and elevated temperature stability with S-nitroso-N-acetylpenicillamine (SNAP)-doped Elast-eon E2As polymer. Biomaterials 34:6957-66
Amoako, Kagya A; Montoya, Patrick J; Major, Terry C et al. (2013) Fabrication and in vivo thrombogenicity testing of nitric oxide generating artificial lungs. J Biomed Mater Res A 101:3511-9
Camboni, Daniele; Rojas, Alvaro; Sassalos, Peter et al. (2013) Long-term animal model of venovenous extracorporeal membrane oxygenation with atrial septal defect as a bridge to lung transplantation. ASAIO J 59:558-63
Amoako, Kagya A; Archangeli, Christopher; Handa, Hitesh et al. (2012) Thromboresistance characterization of extruded nitric oxide-releasing silicone catheters. ASAIO J 58:238-46
Camboni, Daniele; Akay, Begum; Pohlmann, Joshua R et al. (2011) Veno-venous extracorporeal membrane oxygenation with interatrial shunting: a novel approach to lung transplantation for patients in right ventricular failure. J Thorac Cardiovasc Surg 141:537-42, 542.e1
Camboni, Daniele; Akay, Begum; Sassalos, Peter et al. (2011) Use of venovenous extracorporeal membrane oxygenation and an atrial septostomy for pulmonary and right ventricular failure. Ann Thorac Surg 91:144-9
Lin, Yu-Chun; Khanafer, Khalil M; Bartlett, Robert H et al. (2011) An Investigation of Pulsatile Flow Past Two Cylinders as a Model of Blood Flow in an Artificial Lung. Int J Heat Mass Transf 54:3191-3200
Major, Terry C; Brant, David O; Burney, Charles P et al. (2011) The hemocompatibility of a nitric oxide generating polymer that catalyzes S-nitrosothiol decomposition in an extracorporeal circulation model. Biomaterials 32:5957-69

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