Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats
Introduction
A major challenge in orthopaedic surgery is the treatment of implant-related infections [1], [2]. Incidence of postoperative infection after arthroplasty or fracture fixation is commonly low and ranges from 0.3 to 3% [3], [4], [5], [6]. The consequences for the patient, however, are tremendous including prolonged hospitalisation with pain and immobilisation, revision surgery and long-term antibiotic therapy [1], [7]. Infection rates depend on risk factors like diabetes, immunosuppression [8], etc. or open fracture in case of injury [9]. Especially in patients with a high-risk profile, suitable prophylactic efforts have to be taken to prevent infection [10], [11]. Modification of the titanium surface structure and antibacterial drug delivery coating of orthopaedic implants are two options to prevent implant-associated infections. The only definite prophylaxis is winning “the race for the surface” [12] by the osteoblasts, since osseointegration prevents adhesion and colonisation by viable bacteria on the implant surface and, therefore, biofilm formation [13]. Recently, we reported a surface modification of titanium alloy implants by plasmachemical oxidation (PCO) that significantly enhances osseointegration [14]. This surface is thought to be useful in uncemented hip and knee replacements in the future.
The aim of the present study was to evaluate the combination of the osseointegrative effect of the PCO-modified implant surfaces with antibacterial gentamicin coatings in a well-established rat osteomyelitis model in vivo [15], [16].
We hypothesized, that gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats compared to an unmodified control.
Section snippets
Implants
40 custom TiAl6V4 rods (Königsee Implantate GmbH, Aschau, Germany), measuring 0.8 mm in diameter and 25 mm in length were used. The following surface modifications were performed for the verum-groups:
First, PCO was used to modify the surface of titanium alloy implants, as published before [14]. In brief, this technique increases the nm-thin passivity film of the titanium alloy implant to a ceramic coating of approximately 5 μm thickness by anodic oxidation during electrolysis accompanied by
Weight of implants and coatings
The mean weight of unprocessed titanium rods was 54.72 mg (±0.024). After PCO to process the bioactive TiOB surfaces, the mean weight increased to 55.29 mg (±0.029) (plus 0.57 mg ± 0.024). After coating with genta-SDS or genta-tan, the weight increased to 55.92 mg (±0.051) and 56.37 mg (±0.084) and respectively. On average, 0.590 mg (±0.036) of genta-SDS and 1.11 mg (±0.061) of genta-tan were deposited per implant.
Evaluation of gentamicin elution
The elution profile over time showed a burst elution within the first 24 h with a
Discussion
This animal model was highly valid and reproducible to evaluate implant-related osteomyelitis with an interobserver homogeneity for the histological and radiological score-analysis. No signs of infection were observed for any parameter in the negative controls (group A), whereas signs of infection were found for all parameters in the positive controls (group B), except 5 sterile swabs at the implant insertion point.
These results for our internal controls confirm the initial data of Lucke et al.
Conclusion
The results of this study demonstrate a high prophylactic effect on implant-related osteomyelitis by gentamicin-SDS and gentamicin-tannic acid coatings of titanium alloy implants. The coatings do not only reduce or suppress bacterial growth, but also prevent bacterial contamination. Suppressed bacterial growth may only delay the onset of implant related osteomyelitis, whereas prevention of implant contamination and biofilm formation by rapid osseointegration is the key for definitive infection
Acknowledgements
This work was supported by Thüringer Aufbaubank through a grant from the “Europäischer Fonds für regionale Entwicklung” [EFRE] (2008 VF 0048).
We thank Dr. G. Schneider, Mrs. K. Otto and Mrs. S. Voigt from the Biomaterials Lab of the Department of Otorhinolaryngology of University Hospital Jena, Germany for the preparation of the histological specimen. Further we would like to thank Prof. T. Knösel, Department of Pathology, Ludwig-Maximilians-University of Munich, Germany for evaluating the
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