Factors Influencing the Injectability and Osteoconductive of the New Compositesof Calcium Sulfate - Based Bone Cement

Introduction: Injectable bone cements based on calcium sulfate and calcium phosphate are potential materials for bone void fillers. Calcium sulfate has been used for many years to produce materials for bone augmentation, and it continues to be the object of interest and research, because the calcium sulfate can be injected like a bone cement material into irregularly shaped bony defects. But this kind of material is too fast for the reconstruction of bony defects. The calcium sulfat e is easily absorbed in the body within 4-6 weeks (1). Calcium phosphate bioglass, has slowly resorption rate, good biocompatibility and can directly bond to bone. The bone-bioglass bonding ability of the former is attributed to the formation of bone-like apatite layer on its surfaces in the living body (2). However, almost all of the bioactive glass-based materials contained large amount of SiO2. It will be more acceptable that the silica-free calcium phosphate bio-glass as a bone substitute. Calcium phosphate glass-based materials without silica contaminations had shown a high potential for implantation due to their chemical composition closed to nature bones. The calcium glasses contained TiO2 (TCPG) cannot be accurately shaped into the bony defects by themselves. The combination of these two mentioned materials, calcium sulfates and calcium glass contain TiO2 (TCPG); can overcome their drawbacks and the limits of their application. These cements are usually injected into the bony defect s through injector. Therefore, it is important to control the parameters such as working time and setting time. In this study, we synthesized the bio -glass by heating the calcium phosphate powder with titanium ions added instead of silica. Different of liquid/powder (L/P) ratios were used the to control the setting time in this study. Physical and mechanical properties were analyzed to evaluate qualities of calcium phosphate glass with titanium ions added. We also investigate the biodegradation behavior of this composite by assessing osteoconductive effect and bone remolding process in a rabbit model. Materials and Methods : Reagent grade of hydro-phosphate acid, tricalcium phosphate and titanium dioxide powder were stirred thoroughly and heated in a platinum crucible at 1000oC. The melt was poured out in a mortar and quenched as the titanium contained calcium phosphate glass (TCPG). TCPG specimens were pulverized and screened to their particle sizes about 76 μm. Meanwhile, hemi hydrate of calcium sulfate (Merk) having same particle size of TCPG was mixed with TCPG in a Teflon container and formed as the composites cement. The cements specimens in different ratios of TCPG and water were stirred and injected into a 50 x 5 x 5 mm 3 mold. The setting time was defined by a Vicat needle (ASTM C191-92). The compressive strength of the cements was measured by using a Shimadzu AGS-500D universal testing machine. Adult New Zealand rabbits average weighed about 3.0 kilograms were used for in vivo study. The rabbits under operative procedures were anesthetized by intravenous injection of Rompun and Ketamin (1:1). Both hind limb were shaved and sterilized with Povidone-Iodine and prepared for surgery in an aseptic manner. The 10 mm depth and 5 mm diameter cylindrical bone voids were created over metaphysis of bilateral medial femoral condyle. The cements were loaded in a sterile 5 cc plastic syringe immediately after mixing. The rabbits were sacrificed at 4, 8, 12 weeks. The specimens were fixed in 70 per cent ethanol and embedded in methylmethacrylate. Sections stained with HE were evaluated with light microscopy. Results: Figure 1 showed the setting times of bone cements that are increased with the amount of TCPG added in the pure calcium sulfate substrate. Setting times of those cements are proportioned to the ratios of water mixing. The cement with 15 wt. % o TCPG having water ratio of 0.15 may obtain its setting time of 50mim. The setting time of the cement in water ratio of 0.2 was between ranges of 24 to 70 min. By increasing water ratio more than 0.3, the cements would set up to 240 min. The Compressive curve, measured from a universal testing machine, is shown in Figure 2 showed the compression strength of pure calcium sulfate is 21.53± 4.40 MPa while cements with addition of TCPG is decreased to 12.40 ± 2.69 MPa. Figure 2 illustrated the calcium sulfate with 15 wt. % of TCPG could obtain the optimal compressive strength. The in vivo results from figure 4-6 showed that there were no fibrous tissue between the material and host tissue had been found by using TCPG 15wt. % cements. At 4 weeks, figure 3 exhibited the evidence of filling material resorption and the invasion of vascular and new-bone formation. At 8 weeks, a large part of the bone void filler was absorbed and accompanies substitute of the new bone formation. At 12 weeks, pure calcium sulfate in the bone defect reached complete resorption with replacement of trabecular bone ingrowths. However, the (TCPG) in composites cement remained in new bone (Fig. 3).