Osteoinductive activity of biocompatible ceramic-BMP(Bone morphogenetic protein) complex. Part 2. Titania (TiO2)-BMP complex.

Bone morphogenetic protein (BMP) was combined with titania (TiO2) to develop a new biomaterial with osteogenetic properties. To evaluate titania as a base material of the titania-BMP complex, firstly the titania were implanted in the subcutaneous tissue of rats, and secondary osteoinductive activity of titania-BMP complex was examined in the heterotopie site.In the first experiment, titania particles (purity: 99.8%) were molded cylindrically, and sintered at 1, 450°C in an electric furnace. The cylindrical sintered titania were 2 mm in diameter and 6 mm in length. These titania were implanted in the dorsal subcutaneous tissue of wistar rats, and as controls titarium was implanted in the same manner. Five weeks after implantation, all the animals were sacrificed, then the tissue around the samples was excised. After fixation in 10% formalin, samples were removed, and the tissue was observed histomorphologically.In the second experiment, BMP was extracted from bovine bone by 6M Urea with 0.5 MCaCl2 using the procedure reported previously. In order tomake porous titania block, titania particles mixed with resin beads were molded spherically and sintered as described before. Five mg of BMP was hound on to porous titania by using 10μl of 10% gelatine solution. The complex was lyophilized and sterilized by EOG, then implanted in the thigh muscle pouch of ddy conventional mice which were sacrificed 4 weeks after implantation. As controls, BMP (5 mg)-gelatine pellets were implanted in the same way. In order to quantitate new bone formation, bone like deposit on soft X-ray films was analyzed by means of roentgenographic and computer image analysis. Furthermore undecalcified ground sections were examined by light microscopy.After 4 weeks of implantation, the titania were surrounded by thin fibrous tissue without inflammatory cells, as were the controls. All the titania-BMP complex induced new bone. On examining the subjects by computer image analysis, no significant differerce appeared between the implantation of titania-BMP complex and controls. In histomorphological observation, woven bone was seen around the titania and in the titania pores, where woven bonecontacted partially.These results suggest that titania has biocompatibility and does not suppress BMP activity. Moreover, titania-BMP complex could be clinically applied.