Antimicrobial Formulations of Absorbable Bone Substitute Materials as Drug Carriers Based on Calcium Sulfate

Abstract

c Substitution of bones is a well-established, necessary procedure to treat bone defects in trauma and orthopedic surgeries. For prevention or treatment of perioperative infection, the implantation of resorbable bone substitute materials carrying antibiotics is a necessary treatment. In this study, we investigated the newly formulated calcium-based resorbable bone substitute materials containing either gentamicin (CaSO 4 -G [Herafill-G]), vancomycin (CaSO 4 -V), or tobramycin (Osteoset). We characterized the released antibiotic concentration per unit. Bone substitute materials were implanted in bones of rabbits via a standardized surgical procedure. Clinical parameters and levels of the antibiotic-releasing materials in serum were determined. Local concentrations of antibiotics were measured using antimicrobial tests of bone tissue. Aminoglycoside release kinetics in vitro per square millimeter of bead surface showed the most prolonged release for gentamicin, followed by vancomycin and, with the fastest release, tobramycin. In vivo level in serum detected over 28 days was highest for gentamicin at 0.42 g/ml, followed by vancomycin at 0.11 g/ml and tobramycin at 0.04 g/ml. The clinical parameters indicated high biocompatibility for materials used. None of the rabbits subjected to the procedure showed any adverse reaction. The highest availability of antibiotics at 14.8 g/g on day 1 in the cortical tibia ex vivo was demonstrated for gentamicin, decreasing within 14 days. In the medulla, vancomycin showed a high level at 444 g/g on day 1, decreasing continuously over 14 days, whereas gentamicin decreased faster within the initial 3 days. The compared antibiotic formulations varied significantly in release kinetics in serum as well as locally in medulla and cortex.

Size matters: Effect of granule size of the bone graft substitute (Herafill®) on bone healing using Masquelet's induced membrane in a critical size defect model in the rat's femur

“…Currently Herafill® is mainly used as a carrier for antibiotics (Coraça‐Huber et al, ). Possible indications contain the treatment of osteomyelitis (Franceschini, Di Matteo, Bösebeck, Büchner, & Vogt, ; Gramlich, Walter, Gils, & Hoffmann, ), perioperative infections (Pförringer et al, ) as well as periprosthetic joint infections (Marczak, Synder, Sibiński, Okoń, & Kowalczewski, ). In a clinical trial using Herafill® as biomaterial for the treatment of osteomyelitis, it showed excellent properties as a carrier for antibiotics in the context of septic indications, but also inducing new bone formation (Seyler et al, ).…”

Influence of Absorbable Calcium Sulfate-Based Bone Substitute Materials on Human Haemostasis—In Vitro Biological Behavior of Antibiotic Loaded Implants

“…Internal use of calcium sulfate (CS), also known as plaster of Paris, has been employed for bone reconstruction for more than a century [ 1 ]. While offering high biocompatibility, its influence on coagulation by dissociation has been discussed, but not examined thoroughly to date [ 9 ].…”

“…In this study, two formulations which are commercially available in Germany, as well as a third, prospective formulation containing vancomycin to address MRSA-infections, were compared, regarding their specific effects on blood coagulation after implantation [ 1 ]. The blood coagulation cascade requires calcium ions, and efficiently acts on the activation of platelets [ 2 ].…”

Fabrication of apatite-coated gypsum granules and histological evaluation using rabbits

“…Calcium sulfate has a long history of clinical use as a bone substitute because of its bioresorbable and Ca 2+ releasing properties. In recent studies, the potential for calcium sulfate as a vehicle for local delivery of drugs such as antibiotics and growth factors has been investigated [27][28][29][30][31]. Although calcium sulfate has unique properties suitable for a bone augmentation material, the problems of rapid resorption remain.…”