130,000 Americans die from chronic respiratory disease every year. Currently, several means of respiratory support are being examined as a bridge to lung transplantation, but the duration of support is limited and incapable to provide destination therapy. Thus, our group has been developing compliant, thoracic artificial lungs (cTALs) for this purpose. cTALs are attached directly to the pulmonary circulation and thus require no auxiliary pump or large extracorporeal circuit. cTALs provide full respiratory support, can eliminate pulmonary hypertension if necessary, and cause minimal hematological changes. Our current cTAL can arterialize over 7 L/min of venous blood and has a blood flow resistance less than half of a normal healthy lung. Moreover, a single, uncoated cTAL can be used for 14 days with little to no clot formation. Thus, there is also no change in blood flow resistance and no organ dysfunction due to thromboemboli. The goal for this proposal is to build upon these positive results and expand the safe use of cTALs to beyond two months without replacement and several years with regular, elective device replacement. This would allow the cTAL to be used as destination therapy for a larger group of chronic lung disease patients. To achieve this, we will first optimize the fiber bundle surface area to blood volume ratio (SA:V) to minimize clot formation. Second, we will create a cTAL with endothelial-like, surface-focused anticoagulation (SFA) by combining two promising approaches: ultra-low protein-adsorption poly(carboxybetaine) (pCB) surface coatings and surface nitric oxide (NO) flux. Preliminary in vitro data indicates this combination can completely eliminate platelet binding to the biomaterial surface for at least 8 hours and should, therefore, markedly reduce coagulation during long-term use. The following studies are planned to further develop this approach. First, we will optimize the pCB coatings for artificial lung surfaces. Second, 4 hour rabbit studies with small scale artificial lungs will be performed to determine the effect of fiber bundle SA:V on platelet activation and clot formation. Third, 24 hour sheep experiments will be performed with full-sized, pCB-coated cTALs to determine an ideal NO sweep gas concentration that minimizes platelet adhesion and clot formation while keeping metHb < 5% of total hemoglobin. Lastly, two month sheep experiments will be performed to examine cTAL function with the optimized SA:V, pCB coating, and NO flux rate. At the conclusion of this research, the cTAL should be capable of greater than two months of clinical support without replacement and will pave the way toward artificial lungs capable of several years of support with elective replacement.

Public Health Relevance

The goal for this proposal is to reduce blood clot formation in artificial lungs via simultaneous use of two new means of anticoagulation. These means act only at the blood contact surfaces and thus do not cause patient bleeding. It is our hope this new technology would allow for respiratory support that lasts for months to years.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL089043-07
Application #
9013492
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Harabin, Andrea L
Project Start
2007-04-01
Project End
2018-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
7
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Carnegie-Mellon University
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Sundaram, Harihara S; Han, Xia; Nowinski, Ann K et al. (2014) Achieving One-step Surface Coating of Highly Hydrophilic Poly(Carboxybetaine Methacrylate) Polymers on Hydrophobic and Hydrophilic Surfaces. Adv Mater Interfaces 1:
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Schewe, Rebecca E; Scipione, Christopher N; Koch, Kelly L et al. (2012) In-parallel attachment of a low-resistance compliant thoracic artificial lung under rest and simulated exercise. Ann Thorac Surg 94:1688-94
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Akay, Begum; Foucher, Julie A; Camboni, Daniele et al. (2012) Hemodynamic design requirements for in-series thoracic artificial lung attachment in a model of pulmonary hypertension. ASAIO J 58:426-31
Schewe, Rebecca E; Khanafer, Khalil M; Arab, Aarthi et al. (2012) Design and in vitro assessment of an improved, low-resistance compliant thoracic artificial lung. ASAIO J 58:583-9

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