The influence of porosity on release profiles of antibiotics from calcium phosphate composites was investigated to optimize the duration of treatment. We hypothesized, that by the encapsulation of vancomycin-HCl into biodegradable microspheres prior admixing to calcium phosphate bone cement, the influence of porosity of the cement matrix on vancomycin release could be reduced. Encapsulation of vancomycin into a biodegradable poly(lactic co-glycolic acid) copolymer (PLGA) was performed by spray drying; drug-loaded microparticles were added to calcium phosphate cement (CPC) at different powder to liquid ratios (P/L), resulting in different porosities of the cement composites. The effect of differences in P/L ratio on drug release kinetics was compared for both the direct addition of vancomycin-HCl to the cement liquid and for cement composites modified with vancomycin-HCl-loaded microspheres. Scanning electron microscopy (SEM) was used to visualize surface and cross section morphology of the different composites. Brunauer, Emmett, and Teller-plots (BET) was used to determine the specific surface area and pore size distribution of these matrices. It could be clearly shown, that variations in P/L ratio influenced both the porosity of cement and vancomycin release profiles. Antibiotic activity during release study was successfully measured using an agar diffusion assay. However, vancomycin-HCl encapsulation into PLGA polymer microspheres decreased porosity influence of cement on drug release while maintaining antibiotic activity of the embedded substance.
Our aim was to study the suitability of the ex-vivo human trabecular bone bioreactor ZetOS to test the biocompatibility of calcium phosphate bone cement composites modified with spray dried, drug loaded microspheres. We hypothesized, that this bone bioreactor could be a promising alternative to in vivo assessment of biocompatibility in living human bone over a defined time period. Composites consisting of tetracycline loaded poly(lactic-co-glycolic acid) microspheres and calcium phosphate bone cement, were inserted into in vitro cultured human femora head trabecular bone and incubated over 30 days at 37°C in the incubation system. Different biocompatibility parameters, such as lactate dehydrogenase activity, alkaline phosphatase release and the expression of relevant cytokines, IL-1β, IL-6, and TNF-α, were measured in the incubation medium. No significant differences in alkaline phosphatase, osteocalcin, and lactate dehydrogenase activity were measured compared to control samples. Tetracycline was released from the microspheres, delivered and incorporated into newly formed bone. In this study we demonstrated that ex vivo biocompatibility testing using human trabecular bone in a bioreactor is a potential alternative to animal experiments since bone metabolism is still maintained in a physiological environment ex vivo.
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