Accessible Requires Authentication Published by De Gruyter September 3, 2018

Biomimetic multilayer coatings deliver gentamicin and reduce implant-related osteomyelitis in rats

Steffi Grohmann, Manuela Menne, Diana Hesse, Sabine Bischoff, René Schiffner, Michael Diefenbeck and Klaus Liefeith

Abstract

Implant-related infections like periprosthetic joint infections (PJI) are still a challenging issue in orthopedic surgery. In this study, we present a prophylactic anti-infective approach based on a local delivery of the antibiotic gentamicin. The local delivery is achieved via a nanoscale polyelectrolyte multilayer (PEM) coating that leaves the bulk material properties of the implant unaffected while tuning the surface properties. The main components of the coating, i.e. polypeptides and sulfated glycosaminoglycans (sGAG) render this coating both biomimetic (matrix mimetic) and biodegradable. We show how adaptions in the conditions of the multilayer assembly process and the antibiotic loading process affect the amount of delivered gentamicin. The highest concentration of gentamicin could be loaded into films composed of polypeptide poly-glutamic acid when the pH of the loading solution was acidic. The concentration of gentamicin on the surface could be tailored with the number of deposited PEM layers. The resulting coatings reveal a bacteriotoxic effect on Staphylococcus cells but show no signs of cytotoxic effects on MC3T3-E1 osteoblasts. Moreover, when multilayer-coated titanium rods were implanted into contaminated medullae of rat tibiae, a reduction in the development of implant-related osteomyelitis was observed. This reduction was more pronounced for the multifunctional, matrix-mimetic heparin-based coatings that only deliver lower amounts of gentamicin.


*Corresponding author: Klaus Liefeith, Institute for Bioprocessing and Analytical Measurement Techniques (iba) e.V., Department of Biomaterials, 37308 Heilbad Heiligenstadt, Germany, Phone: +49-3606-671500, Fax: +49-3606-671200

Acknowledgments

We thank Dr. Maria Gall and Martin Stibaner (Institute for Laboratory Animal Science, University Hospital Jena) for their support in surgery and data collection, Dr. G. Schneider and Mrs. S. Voigt (Biomaterials Lab, Department of Otorhinolaryngology, University Hospital Jena, Germany) for the preparation of the histological specimen and Thomas Lehmann (Institute for Laboratory Animal Science, University Hospital Jena) for the statistical analyses.

  1. Research funding: This work was supported by the Federal Ministry of Education and Research of Germany (BMBF grant No 03WKCB01E).

  2. Conflicts of interest: The authors declare no conflicts of interest.

  3. Informed consent: Informed consent is not applicable.

  4. Ethical approval: The research related to the animal use complies with all the relevant national regulations and institutional policies. All experiments were approved by the Animal Care Committee of Thuringia (Reg. No. 02-062/13).

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Received: 2018-03-20
Accepted: 2018-07-16
Published Online: 2018-09-03
Published in Print: 2019-08-27

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