New colloidal fabrication of bioceramics with controlled porosity for delivery of antibiotics

Bone tissue regeneration with bioceramics-based biomaterial can suffer from associated bone infections. The objective of this study was to develop new antibiotics drug delivery systems, composed of ceramics matrix with a controlled porosity aiming at releasing the antibiotics loaded in the matrix, in the bone implantation site and in a controlled way. Synthesis of the ceramics matrix is based on a colloidal approach. First, the heterocoagulation of hydroxyapatite nanoparticles (HA) and polymethylmethacrylate microspheres (PMMA) provides the control of the porosity in HA matrix. With constant size of microspheres and HA/PMMA ratio, the sintering temperature allows the modulation of interconnections porosity and volume. In this study, two sintering temperatures, resulting in two different porosities, are used. Secondly, porous biomaterials are loaded with tetracycline hydrochloride (antibiotics with large spectrum used in treatment of bone infections) by impregnation under vacuum. Control of the porous microstructure allows variation of the loaded quantity of antibiotics and of their release kinetics. The antibacterial properties of the ceramics loaded with antibiotics vary with the porous microstructure, both in terms of bacterial growth in the ceramic surroundings and of bacterial colonization of the ceramic surface. Protein adsorption from surroundings onto the ceramic surface varies depending on the porous structure, however without inducing significant changes of antibacterial properties. Unloaded and loaded porous bioceramics are biocompatible with pre-osteoblastic cells as shown by in vitro evaluation. The investigation of DDS with two different porosities demonstrated the possibility to control the antibiotics loaded quantity and the antibacterial efficiency by varying the matrix porosity. Release kinetics is also affected by changes in ceramic porosity but in a much more limited way.