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Topographical biomaterials instruct bacterial surface attachment and the in vivo host-pathogen response

Manuel Romero, Jeni Luckett, Grazziela Figueredo, Alessandro M. Carabelli, Aurélie Carlier, View ORCID ProfileAliaksei Vasilevich, Steven Vermeulen, David Scurr, Andrew L. Hook, Jean-Frédéric Dubern, David Winkler, Amir Ghaemmaghami, Jan de Boer, View ORCID ProfileMorgan R Alexander, View ORCID ProfilePaul Williams
doi: https://doi.org/10.1101/2020.10.10.328146
Manuel Romero
1National Biofilms Innovation Centre, Biodiscovery Institute and School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
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Jeni Luckett
1National Biofilms Innovation Centre, Biodiscovery Institute and School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
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Grazziela Figueredo
2School of Computer Science, University of Nottingham, Nottingham United Kingdom
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Alessandro M. Carabelli
3Advanced Materials and Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom
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Aurélie Carlier
4Laboratory for Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, the Netherlands
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Aliaksei Vasilevich
5BioInterface Science lab, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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  • ORCID record for Aliaksei Vasilevich
Steven Vermeulen
4Laboratory for Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, the Netherlands
5BioInterface Science lab, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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David Scurr
3Advanced Materials and Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom
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Andrew L. Hook
3Advanced Materials and Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom
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Jean-Frédéric Dubern
1National Biofilms Innovation Centre, Biodiscovery Institute and School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
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David Winkler
6Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Kingsbury Drive, Melbourne, Victoria 3086, Australia and Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia CSIRO Data61, Pullenvale, Australia
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Amir Ghaemmaghami
7School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
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Jan de Boer
5BioInterface Science lab, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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Morgan R Alexander
3Advanced Materials and Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom
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  • ORCID record for Morgan R Alexander
Paul Williams
1National Biofilms Innovation Centre, Biodiscovery Institute and School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
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  • For correspondence: paul.williams@nottingham.ac.uk
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ABSTRACT

The prevention of biofilm development on the surfaces of implanted medical devices is a global challenge for the healthcare sector. Bio-instructive materials that intrinsically prevent bacterial biofilm formation and drive an appropriate host immune response are required to reduce the burden of healthcare associated infections. Although bacterial surface attachment is sensitive to micro- and nano- surface topographies, its exploitation has been limited by the lack of unbiased high throughput biomaterial screens combined with model-based methods capable of generating correlations and predicting generic responses. Consequently, we sought to fill this knowledge gap by using polymer chips (TopoChips) incorporating 2,176 combinatorially generated micro-topographies. Specific surface topographies exerted a profound impact on bacterial pathogen attachment independent of surface chemistry. A strong correlation between local surface landscape, bacterial attachment and biofilm formation was established using machine learning methods to facilitate analysis of specific surface parameters for predicting attachment. In vitro, lead topographies prevented colonization by motile (Pseudomonas aeruginosa and Proteus mirabilis) and non-motile (Staphylococcus aureus and Acinetobacter baumannii) bacterial pathogens. In a murine foreign body infection model, specific anti-attachment topographies were shown to be refractory to P. aeruginosa colonization.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵† joint senior authors

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 10, 2020.
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Topographical biomaterials instruct bacterial surface attachment and the in vivo host-pathogen response
Manuel Romero, Jeni Luckett, Grazziela Figueredo, Alessandro M. Carabelli, Aurélie Carlier, Aliaksei Vasilevich, Steven Vermeulen, David Scurr, Andrew L. Hook, Jean-Frédéric Dubern, David Winkler, Amir Ghaemmaghami, Jan de Boer, Morgan R Alexander, Paul Williams
bioRxiv 2020.10.10.328146; doi: https://doi.org/10.1101/2020.10.10.328146
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Topographical biomaterials instruct bacterial surface attachment and the in vivo host-pathogen response
Manuel Romero, Jeni Luckett, Grazziela Figueredo, Alessandro M. Carabelli, Aurélie Carlier, Aliaksei Vasilevich, Steven Vermeulen, David Scurr, Andrew L. Hook, Jean-Frédéric Dubern, David Winkler, Amir Ghaemmaghami, Jan de Boer, Morgan R Alexander, Paul Williams
bioRxiv 2020.10.10.328146; doi: https://doi.org/10.1101/2020.10.10.328146

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