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Mechanical matching of implant to host minimises foreign body reaction

Alejandro Carnicer-Lombarte, Damiano G. Barone, Ivan B. Dimov, View ORCID ProfileRussell S. Hamilton, Malwina Prater, Xiaohui Zhao, Alexandra L. Rutz, George G. Malliaras, Stephanie P. Lacour, Clare E. Bryant, James W. Fawcett, View ORCID ProfileKristian Franze
doi: https://doi.org/10.1101/829648
Alejandro Carnicer-Lombarte
1John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK
2Department of Physiology Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK
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Damiano G. Barone
1John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK
3Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK
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Ivan B. Dimov
2Department of Physiology Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK
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Russell S. Hamilton
4Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK
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  • ORCID record for Russell S. Hamilton
Malwina Prater
4Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK
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Xiaohui Zhao
4Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK
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Alexandra L. Rutz
5Electrical Engineering Division, Department of Engineering, University of Cambridge, Cambridge CB3 0FA, UK
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George G. Malliaras
5Electrical Engineering Division, Department of Engineering, University of Cambridge, Cambridge CB3 0FA, UK
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Stephanie P. Lacour
6Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronics Interface, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1202 Geneva, Switzerland
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Clare E. Bryant
3Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK
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James W. Fawcett
1John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK
7Centre for Reconstructive Neuroscience, Institute for Experimental Medicine CAS, Prague, Czech Republic
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  • For correspondence: jf108@cam.ac.uk kf284@cam.ac.uk
Kristian Franze
2Department of Physiology Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK
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  • ORCID record for Kristian Franze
  • For correspondence: jf108@cam.ac.uk kf284@cam.ac.uk
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Abstract

Medical implants offer a unique and powerful therapeutic approach in many areas of medicine. However, their lifetime is often limited as they may cause a foreign body reaction (FBR) leading to their encapsulation by scar tissue1–4. Despite the importance of this process, how cells recognise implanted materials is still poorly understood5, 6. Here, we show how the mechanical mismatch between implants and host tissue leads to FBR. Fibroblasts and macrophages, which are both crucially involved in mediating FBR, became activated when cultured on materials just above the stiffness found in healthy tissue. Coating implants with a thin layer of hydrogel or silicone with a tissue-like elastic modulus of ∼1 kPa or below led to significantly reduced levels of inflammation and fibrosis after chronic implantation both in peripheral nerves and subcutaneously. This effect was linked to the nuclear localisation of the mechanosensitive transcriptional regulator YAP in vivo. Hence, we identify the mechanical mismatch between implant and tissue as a driver of FBR. Soft implant coatings matching the mechanical properties of host tissue minimized FBR and may be used as a novel therapeutic strategy to improve long-term biomedical implant stability without extensive modification of current implant manufacturing techniques, thus facilitating clinical translation.

One sentence summary Foreign body reaction to medical implants can be avoided by matching the stiffness of the implant surface to that of the host tissue.

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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 November 04, 2019.
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Mechanical matching of implant to host minimises foreign body reaction
Alejandro Carnicer-Lombarte, Damiano G. Barone, Ivan B. Dimov, Russell S. Hamilton, Malwina Prater, Xiaohui Zhao, Alexandra L. Rutz, George G. Malliaras, Stephanie P. Lacour, Clare E. Bryant, James W. Fawcett, Kristian Franze
bioRxiv 829648; doi: https://doi.org/10.1101/829648
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Mechanical matching of implant to host minimises foreign body reaction
Alejandro Carnicer-Lombarte, Damiano G. Barone, Ivan B. Dimov, Russell S. Hamilton, Malwina Prater, Xiaohui Zhao, Alexandra L. Rutz, George G. Malliaras, Stephanie P. Lacour, Clare E. Bryant, James W. Fawcett, Kristian Franze
bioRxiv 829648; doi: https://doi.org/10.1101/829648

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