surface modification using silica xerogel-chitosan hybrid containing biologically active agents for a bone implant

Abstract

Hybrid coating composed of silica xerogel and chitosan on bone implantable substances was examined as novel surface treatment for the delivery of biologically active agents. Silica xerogel was chosen because of its high surface area and its good bioactivity. Chitosan provides mechanical stability and contributes to control the release rate of the biologically active agents. Thus, the hybrid coatings with various contents of chitosan (0, 30, 50, 70, 100 vol.%) were fabricated through a sol-gel process at room-temperature, and the performance of the hybrid coatings for the biomolecules delivery was investigated by examining their biological properties. When the chitosan composition was 30 %, the hybrid coatings were physically and mechanically stable. The coating layers became more hydrophilic with increasing silica xerogel content, reflecting their good cell affinity such as cell adhesion and migration. Moreover, the alkaline phosphate activity of cells was significantly higher on the hybrid coatings (especially with 30 % chitosan in the hybrid) than on titanium substrates or pure chitosan coatings. The hybrid coatings with various biomolecules were prepared in situ at ambient temperature. Vancomycin and bone morphogenic protein 2 (BMP2) were incorporated into the hybrid coating as the delivered biomolecules. The release of the biomolecules, observed in phosphate buffer solution (PBS) at 37 ℃, was strongly dependent on the composition of the coating material. In this process, each biomolecules had a different release profile. Furthermore, through in vitro tests (in terms of antimicrobial activity and cell differentiation levels for vancomycin and BMP2, respectively), the hybrid coating (containing 30 % of chitosan) was confirmed that the incorporated biomolecules in the hybrid retained their biological activities without any denaturation and enhanced their biological properties. The 30 % chitosan hybrid coating containing BMP2 was also applied on the porous hydroxyapatite scaffold and investigated in terms of biological properties and in vivo performance. The cell differentiation level of the hybrid coating with BMP2 was higher compared to that of the hydroxyapatite substrates. The hybrid coating allowed a comparatively linear release behavior of BMP2 for 42 days. The in vivo study in a rabbit calvarial model was performed and the hybrid coating with BMP2 was compared to a pure porous hydroxyapatite scaffold. New bone formation ratio was evaluated by histomorphometry analysis. In this study, the hybrid coating with BMP2 was successfully applied to the porous hydroxyapatite scaffold and showed a significantly higher value of bone regeneration compared to those of porous hydroxyapatite scaffolds.