Friedrich-Alexander-Universität Erlangen-Nürnberg
Calcium phosphate cements (CPCs) are established for bone repair. Addition of antibiotics is a promising approach to prevent or treat bone infections by local drug administration [1].
In this study, three different apatite-forming CPCs based on clinically approved cements were investigated: TTCP cement (73 wt.% tetracalcium phosphate (TTCP) and 27 wt.% dicalcium phosphate anhydrate (DCPA)), Biocement D (61 wt.% α-tricalcium phosphate (α-TCP), 26 wt.% DCPA, 10 wt.% calcite, 3 wt.% apatite) and α-TCP cement (85 wt.% α-TCP, 12 wt.% calcite, 3 wt.% DCPA).
The cements were mixed with either pure Aqua ad iniectabilia, or solutions containing 40 mg/ml gentamicin respectively 50 mg/ml vancomycin. Initial and final setting times were determined by an Imeter (automated Gillmore needle device), while the change in quantitative phase composition during setting was assessed by in-situ X-ray diffraction (XRD), combined with Rietveld refinement and G-factor (external standard) method [2].
The setting times of all three cements were not affected by vancomycin, but significantly increased by gentamicin. The effect of the antibiotics on the setting reaction differed depending on the cement type. In the TTCP cement, TTCP and DCPA dissolution as well as apatite formation were retarded by gentamicin, while vancomycin had no effect. Apatite formation was retarded by both vancomycin and gentamicin in Biocement D, while it was not affected by any of the antibiotics in the α-TCP cement.
In conclusion, it was proven that no effects on cement hardening need to be considered when vancomycin is added, though apatite formation might be affected in compositions like Biocement D. However, the considerable retarding effect of gentamicin needs to be compensated. Applicable gentamicin-modified cements might be achieved for instance by increasing the amount of accelerator (Na2HPO4).
[1] MP Ginebra et al. Adv Drug Deliv Rev 2012;64(12):1090-110.
[2] D Jansen et al. Cem Concr Res 2011;41: 602-608.
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