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A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling

Nature Biotechnology volume 32, pages 1134–1140 (2014)Cite this article

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Abstract

Thrombosis and biofouling of extracorporeal circuits and indwelling medical devices cause significant morbidity and mortality worldwide. We apply a bioinspired, omniphobic coating to tubing and catheters and show that it completely repels blood and suppresses biofilm formation. The coating is a covalently tethered, flexible molecular layer of perfluorocarbon, which holds a thin liquid film of medical-grade perfluorocarbon on the surface. This coating prevents fibrin attachment, reduces platelet adhesion and activation, suppresses biofilm formation and is stable under blood flow in vitro. Surface-coated medical-grade tubing and catheters, assembled into arteriovenous shunts and implanted in pigs, remain patent for at least 8 h without anticoagulation. This surface-coating technology could reduce the use of anticoagulants in patients and help to prevent thrombotic occlusion and biofouling of medical devices.

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Figure 1: TLP-coated surfaces repel whole human blood.
Figure 2: Whole blood interactions with TLP surfaces.
Figure 3: Stability and thrombogenicity of TLP surfaces.
Figure 4: Thrombogenicity of TLP-coated circuits in a porcine arteriovenous shunt model.

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Acknowledgements

This work was supported by Defense Advanced Research Projects Agency grant N66001-11-1-4180 and contract HR0011-13-C-0025, and the Wyss Institute for Biologically Inspired Engineering at Harvard University. We thank D. Super, R. Cooper, E. Murray and J. Lee for phlebotomy, T. Ferrante for assistance with fluorescence microscopy, H. Kozakewich for assistance with histology evaluation and O. Ahanotu for assistance in preparing surfaces. Scanning electron microscopy and X-ray photoelectron spectroscopy were conducted at the Center for Nanoscale Systems at Harvard University, a member of the National Nanotechnology Infrastructure Network, which is supported by the National Science Foundation (ECS-0335765).

Author information

Author notes

  1. Benjamin D Hatton

    Present address: Present address: Department of Materials Science and Engineering, University of Toronto, Ontario, Canada.,

  2. Daniel C Leslie and Anna Waterhouse: These authors contributed equally to this work.

Authors and Affiliations

  1. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA

    Daniel C Leslie, Anna Waterhouse, Julia B Berthet, Thomas M Valentin, Alexander L Watters, Abhishek Jain, Philseok Kim, Benjamin D Hatton, Elana H Super, Caitlin Howell, Christopher P Johnson, Thy L Vu, Dana E Bolgen, Sami Rifai, Michael Aizenberg, Michael Super, Joanna Aizenberg & Donald E Ingber

  2. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA

    Daniel C Leslie, Philseok Kim, Benjamin D Hatton, Caitlin Howell, Christopher P Johnson, Thy L Vu, Joanna Aizenberg & Donald E Ingber

  3. Harvard Medical School, Boston, Massachusetts, USA

    Daniel C Leslie, Anna Waterhouse, Julia B Berthet, Thomas M Valentin, Alexander L Watters, Abhishek Jain, Anne R Hansen, Michael Super & Donald E Ingber

  4. Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA

    Daniel C Leslie, Abhishek Jain, Michael Super & Donald E Ingber

  5. Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts, USA

    Anna Waterhouse, Julia B Berthet & Anne R Hansen

  6. Animal Research, Boston Children's Hospital, Boston, Massachusetts, USA

    Arthur Nedder & Kathryn Donovan

  7. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA

    Joanna Aizenberg

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Contributions

D.C.L., A.W., J.B.B., T.M.V., A.L.W., A.J., M.A., M.S., J.A. and D.E.I. designed the research. D.C.L., A.W., J.B.B., T.M.V., A.L.W., A.J., P.K., B.D.H., E.H.S., D.E.B. and S.R. performed experiments. D.C.L., A.W., J.B.B., T.M.V., A.L.W., A.J., E.H.S., M.A., M.S., J.A. and D.E.I. analyzed data. C.H., C.P.J., T.L.V., M.A. and J.A. designed, performed and analyzed the PFD leaching study. D.C.L., A.W., J.B.B., A.N., K.D., D.E.B., A.R.H., M.S. and D.E.I. designed, performed and analyzed the in vivo study. D.C.L., A.W., A.L.W., M.A., M.S., J.A. and D.E.I. wrote the paper with input from all authors.

Corresponding author

Correspondence to Donald E Ingber.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–12, Supplementary Tables 1 and 2 and Supplementary Note 1 (PDF 1086 kb)

Supplementary Movie 1

Adhesion of human blood on untreated control acrylic. Movie of human whole blood anticoagulated with 3.2% sodium citrate)adhering to an uncoated control acrylic surface. (MOV 2345 kb)

Supplementary Movie 2

Repulsion of human blood by TLP acrylic. Movie of human whole blood (anticoagulated with 3.2% sodium citrate) repelled by a TLP acrylic surface. (MOV 1572 kb)

Supplementary Movie 3

Repulsion of human blood by TLP acrylic and polypropylene. Movie of TLP acrylic (left) and control acrylic (right) being immersed in human blood, showing no adhesion on TLP. The blood is then poured out of the TLP (left) and control (right) polypropylene (PP)tubes, again showing no adhesion of blood on the TLP surface. (MOV 62666 kb)

Supplementary Movie 4

Gecko maintains adhesion to a control acrylic cylinder as it is slowly tilted from horizontal to vertical. (MOV 10737 kb)

Supplementary Movie 5

Gecko fails to adhere to a TLP-coated acrylic cylinder as it is slowly tilted from horizontal to vertical. (MOV 6433 kb)

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Leslie, D., Waterhouse, A., Berthet, J. et al. A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling. Nat Biotechnol 32, 1134–1140 (2014). https://doi.org/10.1038/nbt.3020

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