Release of Antibiotics Out of a Moldable Collagen-β-Tricalciumphosphate-Composite Compared to Two Calcium Phosphate Granules

Abstract

Bacterial bone infections after revision surgeries and diseases, like osteomyelitis, are still a challenge with regard to surgical treatments. Local bone infections were treated with antibiotics directly or by controlled drug-releasing scaffolds, like polymethylmethacrylate (PMMA) spheres, which have to be removed at a later stage, but there is a risk of a bacterial contamination during the removement. Therefore, biomaterials loaded with antibiotics for controlled release could be the method of choice: The biomaterials degrade during the drug release, therefore, there is no need for a second surgery to remove the drug eluting agent. Even non-resorbable bone materials are available (e.g., hydroxyapatite (HA)) or resorbable bone graft materials (e.g., beta-tricalcium phosphate (β-TCP)) that will be replaced by newly formed bone. Composite materials with organic additives (e.g., collagen) supports the handling during surgery and enhances the drug loading capacity, as well as the drug releasing time. The purpose of this study was to investigate the loading capacity and the release rate of Vancomycin and Gentamicin on TCP and HA granules in the shape of a degradable scaffold compared to composite materials from TCP mixed with porcine collagen. Its antibacterial efficacy to a more elementary drug with eluting in aqueous solution was examined. The loading capacity of the biomaterials was measured and compared according to the Minimum Inhibition Concentration (MIC) and the Minimum Biofilm Eradication Concentration (MBEC) of a bacterial biofilm after 24 h aging. Antibiotic elution and concentration of gentamycin and vancomycin, as well as inhibition zones, were measured by using the Quantitative Microparticle Systems (QMS) immunoassays. The antibiotic concentration was determined by the automated Beckman Coulter (BC) chemistry device. For examination of the antibacterial activity, inhibition zone diameters were measured. Generally, the antibiotic release is more pronounced during the first couple of days than later. Both TCP granules and HA granules experienced a significantly decline of antibiotics release during the first three days. After the fourth day and beyond, the antibiotic release was below the detection threshold. The antibiotic release of the composite material TCP and porcine collagen declined less drastically and was still in the frame of the specification during the first nine days. There was no significant evidence of interaction effect between antibiotic and material, i.e., the fitted lines for Gentamycin and Vancomycin are almost parallel. During this first in vitro study, β-TCP-Collagen composites shows a significantly higher loading capacity and a steadily release of the antibiotics Gentamycin and Vancomycin, compared to the also used TCP and HA Granules.