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Carbonic anhydrase immobilized on hollow fiber membranes using glutaraldehyde activated chitosan for artificial lung applications

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Abstract

Extracorporeal CO2 removal from circulating blood is a promising therapeutic modality for the treatment of acute respiratory failure. The enzyme carbonic anhydrase accelerates CO2 removal within gas exchange devices by locally catalyzing HCO3 − into gaseous CO2 within the blood. In this work, we covalently immobilized carbonic anhydrase on the surface of polypropylene hollow fiber membranes using glutaraldehyde activated chitosan tethering to amplify the density of reactive amine functional groups for enzyme immobilization. XPS and a colorimetric amine assay confirmed higher amine densities on the chitosan coated fiber compared to control fiber. Chitosan/CA coated fibers exhibited accelerated CO2 removal in scaled-down gas exchange devices in buffer and blood (115 % enhancement vs. control, 37 % enhancement vs. control, respectively). Carbonic anhydrase immobilized directly on hollow fiber membranes without chitosan tethering resulted in no enhancement in CO2 removal. Additionally, fibers coated with chitosan/carbonic anhydrase demonstrated reduced platelet adhesion when exposed to blood compared to control and heparin coated fibers.

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Acknowledgments

Funding assistance for this work was provided by the National Institutes of Health: RO1HL70051 and T32HL07612403. The surface analysis experiments done at NESAC/BIO were supported by NIH Grant number EB-002027 from the National Institute of Biomedical Imaging and Bioengineering. The Postdoctoral Scholar appointment held by Dr. Jeremy Kimmel was supported by a Gift Award from ALung Technologies and the McGowan Institute for Regenerative Medicine. Recombinant human CA was kindly provided by Dr. David Silverman and Dr. Robert McKenna at the University of Florida.

Disclosures

W. J. Federspiel is a co-founder and shareholder in ALung Technologies.

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Authors and Affiliations

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

    J. D. Kimmel, D. T. Arazawa, S.-H. Ye, V. Shankarraman, W. R. Wagner & W. J. Federspiel

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

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

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

    W. R. Wagner & W. J. Federspiel

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

    W. J. Federspiel

  5. Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    S.-H. Ye, V. Shankarraman & W. R. Wagner

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  1. J. D. Kimmel
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  2. D. T. Arazawa
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  3. S.-H. Ye
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  4. V. Shankarraman
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  5. W. R. Wagner
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  6. W. J. Federspiel
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Corresponding author

Correspondence to W. J. Federspiel.

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Kimmel, J.D., Arazawa, D.T., Ye, SH. et al. Carbonic anhydrase immobilized on hollow fiber membranes using glutaraldehyde activated chitosan for artificial lung applications. J Mater Sci: Mater Med 24, 2611–2621 (2013). https://doi.org/10.1007/s10856-013-5006-2

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  • DOI: https://doi.org/10.1007/s10856-013-5006-2

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