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Kinetics of CO2 exchange with carbonic anhydrase immobilized on fiber membranes in artificial lungs

  • Clinical Applications of Biomaterials
  • Original Research
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Abstract

Artificial lung devices comprised of hollow fiber membranes (HFMs) coated with the enzyme carbonic anhydrase (CA), accelerate removal of carbon dioxide (CO2) from blood for the treatment of acute respiratory failure. While previous work demonstrated CA coatings increase HFM CO2 removal by 115 % in phosphate buffered saline (PBS), testing in blood revealed a 36 % increase compared to unmodified HFMs. In this work, we sought to characterize the CO2 mass transport processes within these biocatalytic devices which impede CA coating efficacy and develop approaches towards improving bioactive HFM efficiency. Aminated HFMs were sequentially reacted with glutaraldehyde (GA), chitosan, GA and afterwards incubated with a CA solution, covalently linking CA to the surface. Bioactive CA-HFMs were potted in model gas exchange devices (0.0119 m2) and tested for esterase activity and CO2 removal under various flow rates with PBS, whole blood, and solutions containing individual blood components (plasma albumin, red blood cells or free carbonic anhydrase). Results demonstrated that increasing the immobilized enzyme activity did not significantly impact CO2 removal rate, as the diffusional resistance from the liquid boundary layer is the primary impediment to CO2 transport by both unmodified and bioactive HFMs under clinically relevant conditions. Furthermore, endogenous CA within red blood cells competes with HFM immobilized CA to increase CO2 removal. Based on our findings, we propose a bicarbonate/CO2 disequilibrium hypothesis to describe performance of CA-modified devices in both buffer and blood. Improvement in CO2 removal rates using CA-modified devices in blood may be realized by maximizing bicarbonate/CO2 disequilibrium at the fiber surface via strategies such as blood acidification and active mixing within the device.

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Acknowledgments

This publication was made possible by Grant Numbers R01 HL70051 and R01 HL117637 from the National Institutes of Health, National Heart, Lung and Blood Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH. This work was also funded by research Grants from the Pennsylvania Department of Health (SAP #4100030667, #4100035341, and #4100041556). The author would like to thank Drs. Christopher D. Boone and Robert McKenna (Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610) for supplying the wild-type hCA II used in these experiments, that was funded in part from the National Institutes of Health (GM25154) award. We would like to recognize the University of Pittsburgh’s McGowan Institute for Regenerative Medicine for support of this study. Primary funding for David Arazawa was provided by the NIH Training Grant (T32-HL076124) at the University of Pittsburgh: Cardiovascular Bioengineering Training Program (CBTP).

Conflict of interest

W. J. Federspiel has an equity interest in Alung Technologies which has licensed portions of the technology described in this manuscript. For all other authors, there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

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Authors and Affiliations

  1. McGowan Institute for Regenerative Medicine, University of Pittsburgh, 3025 East Carson Street, Pittsburgh, PA, 15203, USA

    D. T. Arazawa, J. D. Kimmel & W. J. Federspiel

  2. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA

    D. T. Arazawa, J. D. Kimmel & W. J. Federspiel

  3. Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA

    W. J. Federspiel

  4. Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    W. J. Federspiel

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  1. D. T. Arazawa
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  2. J. D. Kimmel
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  3. W. J. Federspiel
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Correspondence to W. J. Federspiel.

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Arazawa, D.T., Kimmel, J.D. & Federspiel, W.J. Kinetics of CO2 exchange with carbonic anhydrase immobilized on fiber membranes in artificial lungs. J Mater Sci: Mater Med 26, 193 (2015). https://doi.org/10.1007/s10856-015-5525-0

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  • DOI: https://doi.org/10.1007/s10856-015-5525-0

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