Keith Cook’s research focuses on applying engineering to critical care medicine. This research melds mechanical, chemical, and material science concepts toward the development of artificial and tissue-based lungs, pulmonary drug delivery, and the computational modeling and prevention of coagulation in medical devices.
- 01 Faculty
- 02 Projects
- 03 Research team
- 04 Publications
- 05 Media mentions
Current research projects in his group include thoracic artificial lungs, biofabricated tissue-based lungs, new biomaterial approaches for reducing coagulation at artificial surfaces, and perfluorocarbon emulsions for pulmonary drug delivery. Of note, his laboratory was the first to produce 24-hour, one-week, and 30-day in vivo studies of thoracic artificial lungs, and his group is working on an artificial lung intended as destination therapy for years of respiratory support. Professor Cook currently serves as the Faculty Director of the Bioengineered Organs Initiative at CMU and is a fellow of the American Institute for Medical and Biological Engineering.
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Keith Cook’s research interests include: artificial lungs; hemodynamics; pulmonary drug delivery; liquid ventilation; right ventricular function; and critical care medicine.
Our laboratory works on the fabrication of lungs composed of 100% biological materials. These lungs have a scaffold consisting of collagen I that is then seeded with endothelial cells on the blood channels and epithelial cells on the airways. Current work focuses on optimizing the gas exchange membranes, evaluating their performance, computational lung design, and developing manufacturing methods for a human booster lung.
Destination therapy artificial lungs
Only a small fraction of patients who need a lung transplant will ever be placed on the waiting list. Thus, our group is developing permanent means of respiratory support for patients with chronic lung disease. To achieve this, we need to expand the useful lifetime of artificial lungs to allow permanent, home-based support. Projects in this area include development of compact, highly biocompatible artificial lungs; various means to slow blood clotting within these devices; and biofabricated, tissue-based lungs.
Pulmonary drug delivery using perfluorocarbon emulsions
In many lung diseases, direct delivery of inhaled drugs to the lungs is desired, but the diseased airways are blocked by mucus or inflammatory exudates. To overcome this issue, our group emulsifies drugs within perfluorocarbon liquids (PFCs) and delivers these emulsions to the lungs. When instilled in the lung, PFC emulsions penetrate down to the alveolar level, wash out harmful fluids, open airways, provide normal or even enhanced gas exchange, and hasten lung recovery. Current applications include severe respiratory infections and acute lung injury.
Blood-biomaterial interactions: surface coatings, pharmaceuticals, and modeling
Blood begins to clot instantly whenever it touches an artificial material. Over time, this causes failure of numerous blood bearing medical devices, including catheters, grafts, and various artificial organs. Our group works to develop various approaches to passivate biomaterial surfaces in these devices and thus slow coagulation, but without using systemic anticoagulants that can cause bleeding. We are currently exploring the use of zwitterionic surface coatings, surface nitric oxide flux, and highly selective inhibitors of the intrinsic branch of the coagulation cascade.
- Research interests
- Biofabrication of tissue-engineered lungs for long-term, respiratory support
- Research interests
- permanent artificial lung support
- Research interests
- biofabricated lungs
- Research interests
- Destination therapy artificial lungs; surface coatings and systemic anticoagulation to prevent clot formation; preclinical research with chronic sheep model
- Research interests
- artificial kidney redesign
- Research interests
- temporary liver support using artificial lung technologies
- Research interests
- liver defatting optimization using organdies
2018 - Present
- Orizondo RA, Nelson DL, Fabiilli ML, Cook KE. Effects of fluorosurfactant structure and concentration on drug availability and biocompatibility in water-in-perfluorocarbon emulsions for pulmonary drug delivery. Journal of Colloid and Polymer Science, 295 (12): 2413–2422, 2017.
- Nelson DL, Zhao Y, Fabiilli ML, Cook KE. In vitro evaluation of lysophosphatidic acid delivery via perfluorocarbon emulsions to enhance alveolar epithelial repair. Colloids and Surfaces B: Biointerfaces, 169: 411-417, 2018.
- Comber EM, Palchesko RN, Nga WH, Ren X, Cook KE. De Novo Lung Biofabrication: Clinical Need, Construction Methods, and Design Strategy. Translational Research (formerly J.Lab.Clin.Med.) 211:1-18, 2019.
- Lai A, Demarest C, Do-Nguyen C, Ukita R, Skoog DJ, Carleton NM, Amoako KA, Montoya JP, Cook KE. 72-hour in vivo evaluation of nitric oxide generating artificial lung gas exchange fibers in sheep. Acta Biomaterialia 90: 122-131, 2019.
- Ukita R, Wu K, Lin X, Carleton NM, Naito N, Lai A, Do-Nguyen C, Demarest CT, Jiang S, Cook KE. Zwitterionic poly-carboxybetaine coating reduces artificial lung thrombosis in sheep and rabbits. ACTA Biomaterialia 92: 71-81, 2019.
- Belanger A, Decarmine A, Jiang S, Cook K, Amoako KA. Evaluating the Effect of Shear Stress on Graft-To Zwitterionic Polycarboxybetaine Coating Stability Using a Flow Cell. Langmuir 35:1984-1988, 2019.
- Ukita R, Potkay JA, Khanafer K, Cook KE. Advancing front oxygen transfer model for the design of microchannel artificial lungs. ASAIO Journal 66(9):1054-1062, 2020.
- Wilbs J., Kong X, Middendorp S.J., Prince R., Cooke A., Demarest C.T., Abdelhafez M.M., Roberts K, Umei N, Gonschorek P, Lamers C, Deyle K, Rieben R, Cook K.E., Angelillo-Scherrer A., Heinis C. Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs. Nature Communications, 11: 3890, 2020.
- Ukita R, Tipograf Y, Tumen A, Donocoff R, Stokes JW, Foley NM, Talackine J, Cardwell NL, Rosenzweig EB, Cook KE, Bacchetta M. Left Pulmonary Artery Ligation and Chronic Pulmonary Artery Banding Model for Inducing Right Ventricular — Pulmonary Hypertension in Sheep, ASAIO J. 67, e44-e48, 2021.
- DeBari MK, Nui X, Scott JV, Griffin MD, Pereira SR, Cook KE, Bin H, Abbott RD. Therapeutic Ultrasound Triggered Silk Scaffold Degradation. Advanced Healthcare Materials. 10, 2100048, 2021.
- Naito N, Ukita R, Wilbs J, Wu K, Lin X, Carleton NM, Roberts K, Jiang S, Heinis C, Cook KE. Combination of Polycarboxybetaine Coating and Factor XII Inhibitor Reduces Clot Formation While Preserving Normal Tissue Coagulation During Extracorporeal Life Support. Biomaterials 272, 120778, 2021.
- R. Ukita, Y. Tipograf, A. Tumen, R. Donocoff, J.W. Stokes, N.M. Foley, J. Talackine, N.L. Cardwell, E.B. Rosenzweig, K.E. Cook, M. Bacchetta. Progression toward decompensated right ventricular failure in the ovine pulmonary hypertension model, ASAIO J, accepted.
- Umei N, Lai A, Miller J, Shin S, Roberts K, AI-Qatarneh S, Ichiba S, Sakamoto A, Cook KE. Establishment and evaluation of a rat model of extracorporeal membrane oxygenation (ECMO) thrombosis using a 3D-printed mock-oxygenator. Journal of Translational Medicine, accepted.
2012 - 2017
- Schewe RE, Khanafer KM, Orizondo RA, Cook KE. Thoracic artificial lung impedance studies using computational fluid dynamics and in vitro models. Annals of Biomedical Engineering 40: 628-36, 2012.
- Pohlmann JR, Akay B, Camboni D, Koch KL, Mervak BM, Cook KE. A low mortality model of chronic pulmonary hypertension in sheep. Journal of Surgical Research 175, 44–48, 2012.
- Chkourko HS, Guerrero-Serna G, Lin X, Dawish N, Pohlmann JR, Cook KE, Martens JR, Rothenberg E, Mussa H, Delmar M. Remodeling of mechanical junctions and of microtubule-associated proteins accompany cardiac connexin43 lateralization. Heart Rhythm 9: 1133-1140. 2012
- Akay B, Foucher JA, Camboni D, Koch KL, Kawatra A, Cook KE. Hemodynamic design requirements for in series thoracic artificial lung attachment in a model of pulmonary hypertension. ASAIO Journal 58: 426-31, 2012.
- Khanafer K, Cook KE, Marafie A. The role of porous media in modeling fluid flow within hollow fiber membranes of the total artificial lung (TAL). Journal of Porous Media 15: 113-122, 2012.
- Schewe RE, Scipione CN, Koch KL, Cook KE. In-parallel attachment of a low resistance compliant thoracic artificial lung under rest and simulated exercise. Annals of Thoracic Surgery 94: 1688-94, 2012.
- Schewe RE, Khanafer KM, Arab A, Mitchell JA, Skoog DJ, Cook KE. Design and in vitro assessment of a compliant thoracic artificial lung. ASAIO Journal 58: 583–589, 2012.
- Scipione CN, Schewe RE, Koch KL, Shaffer A, Iyengar A, Cook KE. Use of a low resistance compliant thoracic artificial lung in the pulmonary artery to pulmonary artery configuration. Journal of Thoracic and Cardiovascular Surgery 145:1660-6, 2013.
- Amoako KA, Montoya JP, Major TC, Handa H, Brant DO, Suhaib AB, Meyerhoff ME, Bartlett RH, Cook KE. Fabrication and in vivo thrombogenicity testing of nitric oxide generating artificial lungs. Journal of Biomedical Materials Research, Part A 101: 3511–3519, 2013.
- Camboni D, Rojas A, Sassalos P, Spurlock D, Koch KL, Menchak S, Singleton J, Boothman E, Haft JW, Bartlett RH, Cook KE. Long-term animal model of venovenous extracorporeal membrane oxygenation with atrial septal defect as a bridge to lung transplantation. ASAIO Journal 59(6):558-63, 2013.
- Orizondo RA, Babcock CI, Fabiilli ML, Fowlkes JB, Younger JG, Cook KE. Characterization of a reverse phase perfluorocarbon emulsion for the pulmonary delivery of tobramycin. Journal of Aerosolized Medicine and Pulmonary Drug Delivery, 27, 392–399, 2014.
- Biscotti MM, Vail E, Cook KE, Kachulis B, Rosenzweig EB, Bacchetta M. Extracorporeal membrane oxygenation with subclavian artery cannulation in awake patients with pulmonary hypertension. ASAIO Journal, 60(6):748-50, 2014.
- Gupta S, Amoako KA, Suhaib A, Cook KE. Multi-modal, surface focused anticoagulation using poly-2-methoxyethylacrylate polymer grafts and surface nitric oxide release. Advanced Materials Interfaces 1, 140012, 2014.
- Sundaram HS, Han X, Nowinski AK, Brault ND, Li Y, Ella-Menye JR, Amoaka KA, Cook KE, Patrick M, Senecal K, Jiang S. Achieving one-step surface coating of highly hydrophilic poly(carboxybetaine methacrylate) polymers on hydrophobic and hydrophilic surfaces. Advanced Materials Interfaces 1, 140071, 2014.
- Orizondo RA, Fabiilli ML, Morales MA, Cook KE. Effects of emulsion composition on pulmonary tobramycin delivery during antibacterial perfluorocarbon ventilation. Journal of Aerosolized Medicine and Pulmonary Drug Delivery 29:251-9, 2016.
- Amoako KA, Suhaib A, Sundaram HS, Jiang S, Cook KE. Multimodal, Biomaterial-Focused Anticoagulation Via Super-low Fouling Zwitterionic Functional Groups Coupled with Anti-Platelet Nitric Oxide Release. Advanced Materials Interfaces 3(6), 1500646, 2016.
- Hong D, Hung H, Wu K, Lin X, Sun F, Zhang P, Liu S, Cook KE, Jiang S. Achieving ultralow fouling under ambient conditions via Si-ARGET ATRP of carboxybetaine. ACS Appl. Mater. Interfaces, 2017, 9 (11), 9255–9259.
- Skoog DJ, Scipione CN, Pohlmann JR, Demos DS, Iyengar A, Schewe RE, Koch KL, Suhaib AB, Cook KE. 14 Day in vivo testing of a compliant thoracic artificial lung, ASAIO Journal 63:644–649, 2017.
2007 - 2011
- Sato H, Griffith GW, Hall CM, Toomasian JM, Hirschl RB, Bartlett RH, Cook KE. Seven day artificial lung testing in an in-parallel configuration. Annals of Thoracic Surgery 84: 988-994, 2007.
- Sato H, Hall CM, Lafayette NG, Pohlmann J, Padiyar N, Toomasian JM, Haft JW, Cook KE. Thirty-day, in parallel artificial lung testing in sheep. Annals of Thoracic Surgery 84: 1136-1143, 2007.
- Zierenberg JR, Fujioka H, Cook KE, Grotberg JB. Pulsatile flow and oxygen transport past cylindrical fiber arrays for an artificial lung: computational and experimental studies. Journal of Biomechanical Engineering 130, 31019-1-31019-12, 2008.
- Kuo AS, Perlman CE, Mockros LF, Cook KE. Pulmonic valve function during thoracic artificial lung attachment. ASAIO Journal 54: 197-202, 2008.
- Sato H, Hall CM, Griffith GW, Johnson KF, Mcgillicuddy JW, Bartlett RH, Cook KE. Large animal model of chronic pulmonary hypertension. ASAIO Journal 54, 396-400, 2008.
- Xu H, Reynolds MM, Cook KE, Toscano JP. 2-hydroxy-5-nitrobenzyl as a diazeniumdiolate protecting group: application in NO-releasing polymers with enhanced biocompatibility. Organic Letters 10: 4593–4596, 2008.
- Kim J, Sato H, Griffith GW, Cook KE. Cardiac output during high afterload artificial lung attachment. ASAIO Journal, ASAIO Journal 55: 73–77, 2009.
- Reoma JL, Rojas A, Kim AC, Khouri JS, Boothman E, Brown K, Grotberg J, Cook KE, Bartlett RH, Hirschl RB, Mychaliska GB. Development of an artificial placenta I: pumpless AV-ECLS in a neonatal sheep model, Journal of Pediatric Surgery 44: 53-9, 2009.
- LaFayette NG, Schewe RE, Montoya PJ, Cook KE. Performance of a Medarray silicone hollow fiber oxygenator. ASAIO Journal 55: 382-387, 2009.
- Reoma JL, Rojas A, Krause E, Obeid NR, Lafayette N, Cook KE, Punch JD, Bartlett RH. Lung physiology during ECMO resuscitation of DCD donors followed by in-vivo assessment of lung function. ASAIO Journal 55: 388-394, 2009.
- Pohlmann JR, Hampton C, Toomasian JM, Romeo A, Cook KE, Bartlett RH. The relationships between air exposure, negative pressure, and hemolysis. ASAIO Journal 55: 469-473, 2009.
- Obeid NR, Rojas A, Reoma JL, Cook KE, Bartlett RH, Punch JD. Organ donation after cardiac determination of death (DCDD): a swine model. ASAIO Journal 55:562–568, 2009.
- Kuo AS, Sato H, Reoma JL, Cook KE. Pulmonary system impedance and right ventricular function. Cardiovascular Engineering 9:153–160, 2009.
- Rojas A, Reoma JL, Krause E, Cook KE, Bartlett RH, Punch JD. Extracorporeal support improves donor renal graft function after cardiac death. American Journal of Transplantation 10: 1365-1374, 2010.
- Akay B, Reoma JL, Camboni D, Pohlmann JR, Albert JM, Kawatra A, Gouch AD, Bartlett RH, Cook KE. In parallel artificial lung attachment at high flows in normal and pulmonary hypertension models. Annals of Thoracic Surgery 90: 259–65, 2010.
- Pohlmann JR, Brant DO, Daul MA, Reoma JL, Kim AC, Johnson KJ, Bartlett RH, Cook KE, Hirschl RB. Total liquid ventilation provides superior respiratory support to conventional mechanical ventilation in a large animal model of severe respiratory failure. ASAIO Journal, 57:1-8, 2011.
- Camboni D, Akay B, Sassalos P, Toomasian JM, Haft JW, Bartlett RH, Cook KE. Use of venovenous extracorporeal membrane oxygenation and an atrial septostomy for pulmonary and right ventricular failure. Annals of Thoracic Surgery 91:144-149, 2011.
- Camboni D, Akay B, Pohlmann JR, Koch KL, Haft JW, Bartlett RH, Cook KE. Veno-venous extracorporeal membrane oxygenation with interatrial shunting: A novel approach to lung transplantation for patients in right ventricular failure. Journal of Thoracic and Cardiovascular Surgery 141:537-42, 2011.
- Rojas-Pena A, Koch KL, Hall CM, Bergin IL, Cook KE. Quantification of thermal spread and burst pressure during endoscopic vessel harvesting (EVH). Journal of Thoracic and Cardiovascular Surgery, 142: 203-208, 2011.
- Rojas A, Hall CM, Cook KE, Bartlett RH, Arenas JD, Punch JD. Timing of heparin and reperfusion temperature during procurement of organs with extracorporeal support in donors after circulatory determination of death. ASAIO Journal 57:368-74, 2011.
- Amoako KA, Cook KE. Nitric oxide-generating silicone as a blood-contacting biomaterial. ASAIO Journal, 57:539–544, 2011.
Prior to 2007
- Vaslef SN, Cook KE, Leonard RJ, Mockros LF, Anderson RW. Design and evaluation of a new, low pressure loss, implantable artificial lung. ASAIO Journal 40: M522-M526, 1994.
- Vaslef SN, Mockros LF, Cook KE, Leonard RJ, Sung JC, Anderson RW. Computer-assisted design of an implantable intrathoracic artificial lung. Artificial Organs 18: 813-817, 1994.
- Cook KE, Makarewicz AJ, Backer CL, Mockros LF, Przybylo HJ, Crawford S.E., Leonard RJ, Mavroudis C. Testing of an intrathoracic artificial lung in a pig model. ASAIO Journal 42: M604-M609, 1996.
- Hocking LM, Debler WR, Cook KE. The growth of leading-edge distortions on a viscous sheet. Physics of Fluids 11: 307-313, 1999.
- Boschetti F, Perlman CE, Cook KE, Mockros LF. Hemodynamic effects of attachment modes and device design of a thoracic artificial lung. ASAIO Journal 46: 42-48, 2000.
- Zwischenberger JB, Anderson CM, Cook KE, Lick SD, Mockros LF, Bartlett RH. Development of an artificial lung: challenges and progress. ASAIO Journal 47: 316-20, 2001.
- Dodge-Khatami A, Backer CL, Holinger LD, Mavroudis C, Cook KE, Crawford SE. Healing of a free tracheal autograft is enhanced by topical VEGF in an experimental rabbit model. Journal of Thoracic and Cardiovascular Surgery 122: 554-561, 2001.
- Cook KE, Maxhimer J, Leonard DJ, Mavroudis C, Backer CL, Mockros LF. Platelet and leukocyte activation and design consequences for thoracic artificial lungs. ASAIO Journal 48: 620-630, 2002.
- Zias EA, Mavroudis C, Cook KE, Makarewicz AJ, Backer CL, Hernandez JM. The effect of pulmonary circulation hemodynamics on right ventricular unloading via the bidirectional Glenn shunt: implications for congenitally corrected transposition repair. Seminars in Thoracic & Cardiovascular Surgery. Pediatric Cardiac Surgery Annual 6:27-32, 2003.
- Boschetti F, Cook KE, Perlman CE, Mockros LF. Blood flow pulsatility effects on oxygen transfer in artificial lungs. ASAIO Journal 49: 678-686, 2003.
- Griffith GW, Toomasian JM, Schreiner RJ, Dusset CM, Cook KE, Osterholtzer KR, Merz SI, Bartlett RH. Hematologic changes during short term tidal flow ECLS. Perfusion 19: 359-363, 2004.
- Toomasian JM, Schreiner RJ, Griffith GW, Meyers DE, Schmidt ME, Hagan SE, Bartlett RH, Cook KE.
- A polymethylpentene fiber gas exchanger for long-term extracorporeal life support. ASAIO Journal, 51: 390-397, 2005.
- Cook KE, Perlman CE, Seipelt R, Backer CL, Mavroudis C, Mockros LF. Hemodynamic and gas transfer properties of a compliant thoracic artificial lung. ASAIO Journal, 51: 404-411, 2005.
- Perlman CE, Cook KE, Seipelt R, Mavroudis C, Backer CL, Mockros LF. Hemodynamic consequences of artificial lung attachment in an in vivo porcine model, ASAIO Journal, 51: 412-425, 2005.
- Carroll CL, Backer CL, Mavroudis C, Cook KE, Goodman DM. Inhaled prostacyclin following surgical repair of congenital heart disease – a pilot study. Journal of Cardiac Surgery 20: 436-439, 2005.
- McGillicuddy JW, Chambers SD, Galligan DT, Hirschl RB, Bartlett RH, Cook KE. In vitro, fluid mechanical effects of thoracic artificial lung compliance. ASAIO Journal 51: 789-794, 2005.
- Sato H, McGillicuddy JW, Griffith GW, Cosnowski AM, Chambers SD, Hirschl RB, Bartlett RH, Cook KE. Effects of artificial lung compliance on in vivo pulmonary system hemodynamics. ASAIO Journal 52: 248-256, 2006.
An interdisciplinary team led by Keith Cook has been awarded $8.7 million dollars from the U.S. Army to create and integrate new technologies to sustain permanent at-home artificial lung support.
US Army CDMRP
Army grant bolsters ongoing artificialorgan research
BME’s Keith Cook, Jana Kainerstorfer, and Howie Choset, along with colleagues at Vanderbilt University and Cornell University, have been awarded an $8.7 million grant from theUS Army CDMRP program. The group is working to create and integrate technologies that enable artificial lungs to transition from temporary support in the ICU to permanent support at home.
Mayo Clinic and Carnegie Mellon University announced today a research agreement to transform organ transplantation. The institutions will bioengineer innovative approaches to address current barriers in organ transplantation.
Keith Cook has been selected to be the next head of the Biomedical Engineering Department (BME) at Carnegie Mellon University’s College of Engineering. The appointment takes effect immediately.
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U.S. Department of Defense
Army grant to fund development of PAS system
BME Interim Head Keith Cook has been awarded a $1.45 million grant from the U.S. Army Congressionally Directed Medical Research programs to develop a pulmonary assist system (PAS) to support military veterans and other patients with long-term, incurable lung disease for a period of months to years.
Rosalyn Abbott’s latest biomaterials research investigates the use of non-invasive, therapeutic ultrasound to trigger and adjust silk scaffold degradation post-implantation.
Biomedical Engineering’s Keith Cook has discovered a novel anticoagulation strategy to keep artificial lung devices from failing due to clot formation, without creating any negative side effects.
Cook featured about “RoboVentilator”
BME’sKeith Cookwas featured inVentureBeaton work to create a low-cost, modular ventilator. Lead by SCS’s Howie Choset, the “RoboVentilator” will help meet the high demand for ventilators exposed by the COVID-19 pandemic, in preparation for possible future respiratory disease outbreaks.
Personal protective equipment generally used in laboratories will aid front-line responders fighting COVID-19.
BME Ph.D. students Jacqueline Scott and Wai Hoe Ng won awards for presenting research at AHA’s 28th Annual Fellows Research Day.
BME Ph.D. students Jacqueline Scott and Wai Hoe Ng won awards for presenting research at AHA’s 28th Annual Fellows Research Day on January 17. Scott won first in clinical, and Ng won second in basic.
There are many ways to make a lung. With so many possible approaches, where do you even start? CMU Ph.D. student Erica Comber has the answer.