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In this study, polymethylmethacrylate-based composite cements containing 40-55.6 wt% micron-sized titania (titanium oxide) particles were developed, and their mechanical, setting, and biological properties evaluated. Three types of composite cement containing 40, 50, and 55.6 wt% silanized titania were designated ST2-40c, ST2-50c, and ST2-56c, respectively. In animal experiments, ST2-50c and ST2-56c were implanted into rat tibiae and solidified in situ. An affinity index was used to evaluate osteoconductivity. Compressive and bending strength of ST2-56c was 147.7+/-3.2 and 69.3+/-7.4; those of the other cements exceeded 100 MPa and 50 MPa, respectively. The affinity indices of ST2-56c were 42.1+/-12.9 at six weeks and 53.4+/-16.6 at 12 weeks, and were significantly higher than for ST2-50c and a commercial PMMA bone cement within 12 weeks. Our data indicate that bone cement containing micron-sized titania particles can be applied to prosthesis fixation as well as vertebroplasty, and ST2-56c is a good candidate cement.

Three types of bioactive polymethylmethacrylate (PMMA)-based bone cement containing nano-sized titania (TiO2) particles were prepared, and their mechanical properties and osteoconductivity are evaluated. The three types of bioactive bone cement were T50c, ST50c, and ST60c, which contained 50 wt% TiO2, and 50 and 60 wt% silanized TiO2, respectively. Commercially available PMMA cement (PMMAc) was used as a control. The cements were inserted into rat tibiae and allowed to solidify in situ. After 6 and 12 weeks, tibiae were removed for evaluation of osteoconductivity using scanning electron microscopy (SEM), contact microradiography (CMR), and Giemsa surface staining. SEM revealed that ST60c and ST50c were directly apposed to bone while T50c and PMMAc were not. The osteoconduction of ST60c was significantly better than that of the other cements at each time interval, and the osteoconduction of T50c was no better than that of PMMAc. The compressive strength of ST60c was equivalent to that of PMMAc. These results show that ST60c is a promising material for use as a bone substitute.

Time-dependent strength behavior was investigated for bisphenol-a-glycidyl methacrylate/triethylene glycol dimethacrylate (Bis-GMA/TEGDMA) resin cements combined with glass-ceramic A-W filler treated with various kinds of silane coupling agents. The fracture strength of the composite resin cements was measured by three-point bending as a function of stressing rate in a simulated body fluid (SBF), and thereby the stress-corrosion susceptibility constant was evaluated. The fracture strength was found to depend on the kind of coupling agent used. For the present Bis-GMA/TEGDMA resin, the silane coupling agents without hydrophilic amine groups can be used to obtain good adhesion between resin and A-W filler owing to their nature of co-polymerizing with the resin. On the other hand, all the composite resin cements showed nearly the same degree of stress-corrosion susceptibility whether the A-W fillers were treated or untreated with silane coupling agents. This means that the stress-corrosion susceptibility of the present composite cements is predominantly affected by that of the matrix resin. Thus, the microcrack formation and growth at the resin matrix near particle - resin interface were thought to determine overall time-dependent strength behavior of the composite cements.

The degradation of a new bioactive bone cement (GBC), comprised of an inorganic filler (bioactive MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass beads) and an organic matrix [high-molecular-weight polymethyl methacrylate (PMMA)], was evaluated in an in vivo aging test. Hardened rectangular specimens (20 x 4 x 3 mm) were prepared from two GBC formulations (containing 50% w/w [GBC50] or 60% w/w [GBC60] bioactive beads) and a conventional PMMA bone cement control (CMW-1). Initial bending strengths were measured with the use of the three-point bending method. Specimens of all three cements were then implanted into the dorsal subcutaneous tissue of rats, removed after 3, 6, or 12 months, and tested for bending strength. The bending strengths (MPa) of GBC50 at baseline (0 months), 3, 6, and 12 months were 136 +/- 1, 119 +/- 3, 106 +/- 5 and 104 +/- 5, respectively. Corresponding values were 138 +/- 3, 120 +/- 3, 110 +/- 2 and 109 +/- 5 for GBC60, and 106 +/- 5, 97 +/- 5, 92 +/- 4 and 88 +/- 4 for CMW-1. Although the bending strengths of all three cements decreased significantly from 0 to 6 months, those of GBC50 and GBC60 did not change significantly thereafter, whereas that of CMW-1 declined significantly between 6 and 12 months. Thus, degradation of GBC50 and GBC60 does not appear to continue after 6 months, whereas CMW-1 degrades progressively over 12 months. Moreover, the bending strengths of GBC50 and GBC60 (especially GBC60) were significantly higher than that of CMW-1 throughout. It is believed that GBC60 is strong enough for use under weight-bearing conditions and that its mechanical strength is retained in vivo; however, its dynamic fatigue behavior will need assessment before application in the clinical setting., (Copyright 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 68B: 132-139, 2004)

A new bioactive bone cement (designated GBC), which is a polymethyl methacrylate- (PMMA-) based composite consisting of bioactive glass beads as an inorganic filler and high-molecular-weight PMMA (hPMMA) as an organic matrix, has been developed. The bioactive glass beads consist of MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass. The purpose of the present study was to evaluate the effect of CaF(2) on osteoconductivity and to evaluate the degree of cement degradation with time. Three different types of cement were prepared. GBC(F +), which has been previously described, consisted of CaF(2)-containing bioactive glass beads and hPMMA. GBC(F -) consisted of CaF(2)-free bioactive glass beads and hPMMA. The third cement was hPMMA itself (as a reference material). These three types of cement were packed into the intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index calculated as the length of bone in direct contact with the cement surface expressed as a percentage of the total length of the cement surface. Rats were killed at 4, 8, 25, and 52 weeks after implantation, and the affinity index was calculated for each type of cement at each time point. Histologically, new bone had formed along the surface of both GBC(F +) and GBC(F -) within 4 weeks, whereas hPMMA had little contact with bone, and an intervening soft tissue layer between bone and cement was detected. No significant difference in affinity index was found between GBC(F +) and GBC(F -) at any of the time points studied, although GBC(F -) showed higher affinity indices than GBC(F +) at 8, 25, and 52 weeks. The affinity indices for GBC(F +) and GBC(F -) were significantly higher than those for hPMMA at all time points. With GBC(F +) and GBC(F -), significant increases in the affinity indices were found as the implantation period increased, and the affinity index values at 52 weeks reached more than 70%. In hPMMA, no significant increase in affinity index was observed up to 52 weeks, and the value at 52 weeks was less than 30%. Although no significant difference in affinity index was found between GBC(F +) and GBC(F -), GBC(F -) is conclusively better than GBC(F +) because diseases such as chronic fluorosis might be caused by CaF(2)-containing glass beads. Regarding the cement degradation of both GBC(F +) and GBC(F -), the degree of the degradation at 25 weeks was the same as that at 52 weeks. Therefore, the cement degradation does not appear to proceed rapidly. Further studies are needed to better understand the degradation process., (Copyright 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 65B: 262-271, 2003)

We have developed two types of polymethylmethacrylate (PMMA)-based bioactive bone cements containing bioactive glass beads (designated GBC) or apatite-wollastonite containing glass-ceramic powder (designated AWC) as the filler. A new method was used to evaluate the bone-cement interfacial strength of these bioactive bone cements. Two types of bioactive bone cements (GBC and AWC) and PMMA cement (CMW-1) were put in a frame attached to the smooth tibial metaphyseal cortex of the rabbit and polymerized in situ. The load required to detach the cement from the bone was measured at 4, 8, and 16 weeks after implantation. The interfacial tensile strength of GBC and AWC showed significantly higher values than PMMA cement from 4 weeks, and increased with time. For GBC, strength reached a maximum value of 12.39 +/- 1.79 kgf 16 weeks after implantation. Histological examination of rabbit tibiae up to 16 weeks demonstrated no intervening layer between the bioactive bone cements and the bone, whereas fibrous tissue was observed at the interface between the PMMA cement and the bone. From this study, we conclude that PMMA-based bioactive bone cements have a relatively higher adhesiveness at the interface than the conventionally used PMMA cement, showing potential as a promising alternative., (Copyright 2002 Wiley Periodicals, Inc.)

We developed new composites consisting of comparatively high molecular weight poly(methyl methacrylate) (hPMMA) and delta-alumina powder or alpha-alumina powder (designated delta-APC and alpha-APC, respectively) that allowed direct bone formation on their surfaces in vivo. delta-Alumina powder was manufactured by the fusing and quenching of pulverized alumina powder. It was composed mainly of delta-crystal phases of alumina. The purpose of this study was to evaluate the static mechanical properties and biological properties of these composites. The hPMMA itself was used as a reference material. The bending strength and Young's modulus of both delta-APC and alpha-APC were significantly higher than those of hPMMA, and the alumina composites are believed to be strong enough for use under weight-bearing conditions. The three types of composites were packed into the intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index. Rats were sacrificed 4 and 8 weeks after surgery. The affinity index, equal to the length of bone in direct contact with the composite surface and expressed as a percentage of the total length of the composite surface, was calculated for each composite at each interval. Histologically, new bone had formed along the surfaces of both delta-APC and alpha-APC within 4 weeks. The affinity indices for both delta-APC and alpha-APC increased significantly with time up to 8 weeks. At 8 weeks, the affinity index for delta-APC was significantly higher than the indices for alpha-APC and hPMMA. This study revealed that the excellent osteoconductivity of delta-APC was due to the delta-crystal phases of alumina and the high molecular weight of hPMMA. delta-APC shows promise as a base for developing a highly osteoconductive and mechanically strong biomaterial., (Copyright 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 585-591, 2002)

New bioactive composites consisting of partially crystallized glass beads as inorganic fillers and poly(methyl methacrylate) (PMMA) as an organic matrix were developed. Two kinds of partially crystallized glass beads, designated Cry820 and Cry850, were newly prepared by the heating of MgO-CaO-SiO(2)-P(2)O(5) glass at 820 and 850 degrees C, respectively. The glass beads were mixed with PMMA to form two new composites designated Cry820C and Cry850C, respectively. The goal of this study was to produce a highly osteoconductive and mechanically strong composite cement with these new fillers. A previously reported composite cement designated AWC, which was composed of apatite- and wollastonite-containing glass ceramic (AW-GC) as a powder filler and the same PMMA polymer used in the new composites, was used as a reference material. The quantity of filler added to each composite was 70 wt %. The bending strength of Cry820C was significantly higher than that of Cry850C. Composites were packed into intramedullary canals of rat tibiae to evaluate their osteoconductivity, as determined by an affinity index. The affinity index, which equaled the length of bone in direct contact with the composite surface expressed as a percentage of the total length of the composite surface, was calculated for each composite. The rats were euthanized at 4, 8, and 25 weeks after implantation. At each time interval studied, Cry820C showed a significantly higher affinity index than AWC up to 25 weeks after implantation. Cry850C showed a significantly higher affinity index than AWC up to 8 weeks and a higher affinity index than AWC at 25 weeks, although the difference was not significant. The values for each composite increased significantly with time up to 25 weeks. Our study revealed that the higher osteoconductivity of the new composites was due to the larger quantity of the glassy phase of the crystallized glass beads at the composite surface and the lower solubility of the PMMA powder to methyl methacrylate monomer. In addition, the spherical shape of the crystallized glass beads gave the new composites strong enough mechanical properties to be useful under weight-bearing conditions. The new composites show promise as alternatives, with improved properties, to conventional PMMA bone cement., (Copyright 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 556-563, 2002)

A new bioactive bone cement (designated GBC), which is a polymethyl methacrylate (PMMA)-based composite consisting of bioactive glass beads as an inorganic filler and high molecular-weight PMMA as an organic matrix, has been developed. The purpose of the present study was to evaluate the effect of the filler content on the mechanical properties and osteoconductivity of GBC, to decide the most suitable filler proportion, and to evaluate the degree of cement degradation with time. The bioactive beads, consisting of MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass, were added to the cement in various proportions (40-70 wt %). The bending strength of GBC did not differ among the proportions (approximately 136 MPa), but the elastic modulus of bending of GBC increased as the glass bead filler content increased (approximately 4.1-7.2 GPa). The all types of GBC were packed into the intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index calculated as the length of bone in direct contact with the cement surface expressed as a percentage of the total length of the cement surface. Rats were sacrificed at 4, 8, 25, and 39 weeks after implantation, and the affinity index was calculated for each type of GBC at each time point. Histologically, new bone had formed along the surface of all types of GBC within 4 weeks, even in GBC containing only 40 wt % of glass beads. The affinity indices of GBC tended to increase as the proportion of glass bead filler increased and as the implantation period increased. In GBC containing 60 or 70 wt % of glass beads, significant rapid increases in the affinity indices were found from 4 to 8 weeks, and the high values (approximately 70%) were maintained up to 39 weeks. A sign of glass bead degradation was observed at the bone-cement interface in the rat tibiae at 39 weeks. We conclude that, when mechanical properties and osteoconductivity are both taken into consideration, GBC containing 60 or 70 wt % of glass beads is the most suitable formulation, but that further studies are needed to investigate and overcome the degradation., (Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 59: 225-232, 2002)

A new bioactive bone cement, designated GBC, has been developed. It consists of polymethyl methacrylate (PMMA) as an organic matrix and bioactive glass beads as an inorganic filler. The bioactive beads, consisting of MgO--CaO--SiO(2)--P(2)O(5)--CaF(2) glass, have been newly designed, and a novel PMMA powder was selected. The purpose of the present study was to evaluate the effects on mechanical properties and osteoconductivity of adding a phosphoric ester (PE) monomer to the cement as an adhesion-promoting agent. Four kinds of cements were prepared: GBC, GBC with PE (designated GBC/PE), a cement consisting of the same PMMA used in GBC with apatite- and wollastonite-containing glass-ceramic (AW-GC) powder (designated AWC), and AWC with PE (designated AWC/PE). Each filler was added to the cement at 70 wt %. Adding PE to either GBC or AWC resulted in increases in the bending strength and decreases in the Young's modulus compared with the unmodified cements. Cements were packed into the intramedullar canals of rat tibiae to evaluate osteoconductivity as determined by an affinity index. Rats were sacrificed at 4 and 8 weeks after operation. The affinity index (length of bone in direct contact with the cement expressed as a percentage of the total length of the cement surface) was calculated for each cement. Adding PE to either GBC or AWC resulted in significant increases in the affinity index compared with the unmodified cements. The affinity index for GBC was significantly higher than that of AWC, and that for GBC/PE was also significantly higher than that of AWC/PE. The affinity indices for each cement increased significantly with time up to 8 weeks. Our study revealed that the higher osteoconductivity of GBC/PE was due to the large alkyl group in the PE monomer, to the hydrophilicity of the phosphoric acid in the PE monomer, and to the higher bioactivity of the bioactive glass beads at the cement surface. GBC/PE shows promise as an alternative bone cement with improved properties compared with conventional PMMA bone cement., (Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 56: 571--577, 2001)

A bioactive bone cement (designated GBC), consisting of bioactive glass beads as an inorganic filler and poly(methyl methacrylate) (PMMA) as an organic matrix, has been developed. The purpose of the present study was to examine the effect of the size of the glass beads added as a filler to GBC on its mechanical properties and osteoconductivity. Serial changes in GBC with time were also examined. Four different sizes of beads (mean diameters 4, 5, 9, and 13 microm) consisting of MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass were added to four GBC mixes in a proportion of 70 wt %. The bending strength of GBC increased as the mean size of the glass beads decreased. The four GBC mixes were packed into the intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index. Rats were sacrificed at 4 and 8 weeks after surgery. The affinity index, which equaled the length of bone in direct contact with the cement surface expressed as a percentage of the total length of the cement surface, was calculated for each cement at each interval. Histologically, new bone had formed along the surface of all types of GBC within 4 weeks. At each time interval, there was a trend for the affinity index of GBC to increase as the mean glass bead size decreased. The affinity indices for all types of GBC increased significantly with time up to 8 weeks. The handling properties of GBC were comparable to those of conventional PMMA bone cement. We concluded that, considering both mechanical properties and osteoconductivity, GBC made with smaller sized glass beads as filler was the most suitable cement. GBC shows promise as an alternative bone cement with improved properties compared to conventional PMMA bone cement., (Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 56: 452-458, 2001)

A novel bioactive bone cement (GBC) was developed with newly designed bioactive MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass beads as the inorganic filler and high molecular weight poly(methyl methacrylate) as the organic matrix. The purpose of this study was to examine the relationship between the amount of the silane coupling agent (gamma-methacryloxy propyl trimethoxy silane) used to treat the glass beads and the mechanical and biological properties of the resultant bone cement. Serial changes in the cement over time were also investigated. Five different kinds of cement, in which the glass beads were treated with different amounts of the coupling agent, were prepared. The quantities of the coupling agent were 0 (control), 0.1, 0.2, 0.5, and 1.0% (w/w) of the glass beads, and the cements were designated GBCs0, GBCs0.1, GBCs0.2, GBCs0.5, and GBCs1.0, respectively. After soaking in water at 75 degrees C for 5 days, GBCs0.1 and GBCs0.2 had significantly higher bending strengths than the other cements. Each GBC was packed into intramedullar canals of rat tibiae to evaluate osteoconductivity, as determined by affinity indices. Rats were killed 4 and 8 weeks after the operation. The affinity index was calculated for each GBC and equaled the length of bone in direct contact with the cement and was expressed as a percentage of the total length of the cement surface. Histologically, new bone had formed along all of the GBC surfaces within 4 weeks. At each time interval, a decreasing trend in the affinity index of GBC was found as the amount of the coupling agent increased. At 8 weeks, no significant change in the affinity index occurred when the amount of the coupling agent increased from 0 to 0.2%, whereas a significant decrease in the affinity index was observed when the amount of the coupling agent increased from 0 to 0.5 or 1.0%. The affinity indices for all the GBCs increased significantly up to 8 weeks. When both the mechanical properties and osteoconductivity were taken into consideration, GBCs0.1 and GBCs0.2 were the best cements, and they showed excellent osteoconductivity and strong enough mechanical properties for clinical use., (Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 55: 277-284, 2001)

Previously we developed a composite consisting of apatite and wollastonite containing glass-ceramic (AW-GC) powder and bisphenol-a-glycidyldimethacrylate (Bis-GMA)-based resin (designated AWC), and demonstrated that AWC showed direct contact with living bone. Another new composite consisting of mainly the delta-crystal phase of alumina bead powder and Bis-GMA-based resin (designated ABC) was developed. Although alumina ceramics are bioinert and a composite filled with the pure alpha-crystal phase of alumina powder (designated alphaALC) did not allow direct bone formation in vivo, ABC was shown to have excellent osteoconductivity. One purpose of this study was to investigate whether AW-GC powder in a composite promotes osteoblastic differentiation of rat bone marrow cells as AW-GC bulk did. Another purpose was to evaluate the effects of the delta-crystal phase of alumina powder in a composite on osteoblastic differentiation. In a cell culture with dexamethasone, alkaline phosphatase (AP) activity at both days 7 and 14, and the levels of osteocalcin mRNA and alpha1(I) collagen mRNA at day 14 and osteopontin mRNA at day 7, were highest on AWC, followed by ABC, and finally alphaALC. Scanning electron microscopy showed more abundant mineralized globules and a fibrous collagen matrix on AWC at day 14, followed by ABC. In a cell culture without dexamethasone, AP activity at both days 7 and 14, and the level of osteopontin mRNA at day 7, were higher on ABC than on any other composite, whereas osteocalcin mRNA could not be detected. These results indicate that AW-GC powder in a composite promotes osteoblastic differentiation of bone marrow cells intensively when supplemented with dexamethasone. The delta-crystal phase of alumina powder in a composite promotes greater osteoblastic differentiation than the alpha-crystal phase of alumina powder., (Copyright 2001 John Wiley & Sons, Inc.)

A new bioactive bone cement (designated GBC), consisting of bioactive glass beads as an inorganic filler and polymethylmethacrylate (PMMA) as an organic matrix, has been developed. The purpose of the present study was to examine the effect of the amount of glass bead filler added to GBC on its mechanical and biological properties, and to decide the most suitable content of filler. Serial changes in GBC with time were also examined. The newly designed bioactive beads, consisting of MgO-CaO-SiO2-P2O5-CaF2 glass, were added to the cement in the proportions 30, 40, 50, 60, and 70 wt %. These cements were designated GBC30, GBC40, GBC50, GBC60, and GBC70, respectively. The compressive strength and the elastic modulus of bending of GBC increased as the glass bead content increased. The various types of GBC were packed into the intramedullar canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index calculated as the length of bone in direct contact with the cement expressed as a percentage of the total length of the cement surface. Rats were killed at 4 and 8 weeks after the operation and the affinity index was calculated for each type of GBC. Histologically, new bone had formed along the surface of all types of GBC within 4 weeks, even in GBC30 containing only 30 wt % of glass beads. At each time interval studied, there was a trend for the affinity index of GBC to increase as the glass bead filler content increased. There was no significant increase of affinity index between GBC60 and GBC70. The affinity indices for all types of GBC increased significantly with time up to 8 weeks. The handling properties of GBC were comparable to those of conventional PMMA bone cement. We conclude that when mechanical properties and osteoconductivity are both taken into consideration, GBC60 is the most suitable formulation; it shows excellent osteoconductivity and sufficient mechanical strength for clinical use.

The purpose of this study was to elucidate the effect of amount of ceramic cement powder on drug release from bioactive bone cement. The associated bone-bonding strength was also investigated. The bioactive bone cement under investigation consisted of bisphenol-alpha-glycidyl methacrylate (Bis-GMA), triethylene-glycol dimethacrylate (TEGDMA) resin and a combination of apatite- and wollastonite-containing glass-ceramic (A-W GC) powder. A-W GC powder (50%, 70% and 80% w/w) containing 5% cephalexin (CEX) powder hardened within 5 min after mixing with Bis-GMA/TEGDMA resin. The compressive strength of the cement with or without drug increased with increasing the amount of ceramic powder. The compressive strength of the 80% ceramic cement without the incorporation of cephalexin was 194 MPa. This compressive strength was about 3 times higher than that for polymethylmethacrylate cement. After the cement was implanted in the proximal metaphysis of the tibiae of male rabbits, the failure load for the cement was found to increase with increasing of the amount of ceramic powder. This finding suggested that the cement formed a bonding with bone. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 weeks. Drug release profile followed the Higuchi equation initially, but not at later stages. The drug release rate increased with increasing amount of ceramic powder in the mixture. Since the pore volume of the cement increased with increasing of amount of ceramic powder, the drug diffused in the pores between the ceramics particle and polymer matrix. As hydroxyapatite precipitated on the cement surface, the drug release rate decreased, as observed at the later release stage. These results suggest that varying the amount of ceramic powder in the cement system could control the drug release rate from bioactive bone cement.

A new bioactive bone cement (designated GBC) consisting of polymethyl methacrylate (PMMA) as an organic matrix and bioactive glass beads as an inorganic filler has been developed. The bioactive beads, consisting of MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass, have been newly designed, and a novel PMMA powder was selected. The purpose of the present study was to compare this new bone cement GBC's mechanical properties in vitro and its osteoconductivity in vivo with cements consisting of the same matrix as GBC and either apatite- and wollastonite-containing glass-ceramic (AW-GC) powder (designated AWC) or sintered hydroxyapatite (HA) powder (HAC). Each filler added to the cements amounted to 70 wt %. The bending strength of GBC was significantly higher than that of AWC and HAC (p < 0.0001). Cements were packed into intramedullar canals of rat tibiae in order to evaluate osteoconductivity as determined by an affinity index. Rats were sacrificed at 2, 4, and 8 weeks after operation. An affinity index, which equaled the length of bone in direct contact with the cement expressed as a percentage of the total length of the cement surface, was calculated for each cement. At each time interval studied, GBC showed a significantly higher affinity index than AWC or HAC up to 8 weeks after implantation (p < 0.03). The value for GBC increased significantly with time up to 8 weeks (p < 0.006). The handling property of GBC was comparable with that of PMMA bone cement. Our study revealed that the higher osteoconductivity of GBC was due to the higher bioactivity of the bioactive glass beads at the cement surface and the lower solubility of the new PMMA powder to MMA monomer. In addition, it was found that the smaller spherical shape and glassy phase of the glass beads gave GBC strong enough mechanical properties to be useful under weight-bearing conditions. GBC shows promise as an alternative with improved properties to the conventionally used PMMA bone cement., (Copyright 2000 John Wiley & Sons, Inc.)

Three composites consisting of alumina powder dispersed in a bisphenol-a-glycidyl methacrylate (Bis-GMA) matrix were prepared and evaluated to assess the effect of alumina powder content on the mechanical properties and osteoconductivity of the composite. The alumina powder composites (APC) consisted of alumina powder (AL-P) as the inorganic filler dispersed in a Bis-GMA matrix that was solidified by a radical polymerization process. Prior to polymerization the AL-P was mixed with the monomers in proportions of 50%, 70%, and 80% by weight (APC50, APC70, and APC80). A fused silica-glass-filled composite containing 70% glass by weight (SGC70) was used as a control. The compressive and bending strengths, the elastic modulus in bending, and the bending strain of the composites increased as the AL-P content increased. We also evaluated the composites in vivo by implanting them into the medullary canals of rat tibiae. To compare the osteoconductivity of the composites, an affinity index was calculated for each composite; the affinity index equals the length of a bone in direct apposition to the composite and is expressed as a percentage of the total length of the composite surface. Microradiographic examination for periods of up to 26 weeks after implantation revealed that APC50, APC70, and APC80 all exhibited excellent osteoconductivity and made direct contact with the bone with no interposed soft tissues. However, the higher the AL-P content of the composite, the higher the osteoconductivity, especially at 4 weeks after the operation. Moreover, the amount of bone directly apposed to the composite surface increased with time. In contrast, little bone formation was seen on the surface of SGC70, even after 26 weeks. Observation by scanning electron microscope-energy dispersive X-ray microanalysis demonstrated that bone made direct contact with the APC surface through a layer containing calcium, phosphorus, and alumina powder. These results suggest that APC shows promise as a basis for developing mechanically strong and highly osteoconductive composites., (Copyright 2000 John Wiley & Sons, Inc.)

The fact that bisphenol-a-glycidyl methacrylate (bis-GMA)-based cements contain an uncured surface is believed to play an important role when determining the surface curing properties of the cements. Therefore, in the present study, the bone-bonding strength of cement plates having an uncured surface on one side and a cured surface on the other side has been evaluated. These cement plates were composites of a bis-GMA-based resin with either an apatite- and wollastonite-containing glass-ceramic (AW-GC) powder or a hydroxyapatite (HA) powder, respectively designated AWC and HAC. The amount of each of these powders in a composite cement was 70 wt %. We formulate the hypothesis that the uncured surface of a cement plate is bioactive having bone-bonding properties. The goal of the present study was to indicate the bone-bonding strength of the uncured surfaces of AWC and HAC and compare the strength with the respective cured surfaces by a detaching in vivo test, as well as to histologically examine the bone-cement interface. Each plate has been implanted into the tibiae of male Japanese white rabbits, taking care to retain the surface properties, and the so-called "failure load has been measured using a detaching test followed 8 weeks after implantation. The failure load for AWC-plates at the uncured surface (2.05 +/- 1.11 kgf, n = 8) was significantly higher than AWC at its cured surface side (0.28 +/- 0.64 kgf, n = 8). The failure load for HAC-plates at the uncured surfaces (1.40 +/- 0.68 kgf, n = 8) was significantly higher than HAC at its cured surface (0.00 +/- 0.00 kgf, n = 8). Failure loads for AWC at its uncured and cured surfaces were both higher than for HAC, although not significantly. Direct bone formation has been observed histologically for both AWC and HAC on the uncured surfaces, and a Ca-P-rich layer was observed only at the uncured surface of AWC. These findings strongly suggest that uncured surfaces are useful for exposing a bioactive filler on a surface of composites, being very effective in inducing bone bonding., (Copyright 2000 John Wiley & Sons, Inc.)

We developed a composite (ABC) consisting of alumina bead powder as an inorganic filler and bisphenol-a-glycidyl dimethacrylate (Bis-GMA)-based resin as an organic matrix. Alumina bead powder was manufactured by fusing crushed alpha-alumina powder and quenching it. The beads took a spherical form 3 microm in average diameter. The proportion of filler in the composites was 70% w/w. The composite was implanted into rat tibiae and cured in situ. Specimens were prepared 1, 2, 4, and 8 weeks after the operation and observed by transmission electron microscopy. The results were compared with those of a bone composite made of alpha-alumina powder (alpha-ALC). In ABC-implanted tibiae, the uncured surface layer of Bis-GMA-based resin was completely filled with newly formed bonelike tissue 2 weeks after implantation. The alumina bead fillers were surrounded by and in contact with bonelike tissue. No intervening soft tissue was seen. In alpha-ALC-implanted tibiae, a gap was always observed between the alpha-ALC and the bonelike tissue. These results indicate that the ABC has osteoconductivity, although the precise mechanism is still unclear., (Copyright 2000 John Wiley & Sons, Inc.)

We took three types of bioactive bone cement (designated AWC, HAC, and TCPC), each with a different bioactive filler, and evaluated the influence of each filler on the mechanical properties and osteoconductivity of the cement. The cements consisted of bisphenol-a-glycidyl methacrylate-based (Bis-GMA based) monomers as an organic matrix, with a bioactive filler of apatite/wollastonite containing glass-ceramic (AW-GC) or sintered hydroxyapatite (HA) or beta-tricalcium phosphate (beta-TCP) powder. Each filler was mixed with the monomers in proportions of 50, 70, and 80% (w/w), giving a total of nine cement subgroups. The nine subgroups were designated AWC50, AWC70, AWC80, HAC50, HAC70, HAC80, TCPC50, TCPC70, and TCPC80. The compressive and bending strengths of AWC were found to be higher than those of HAC and TCPC for all bioactive filler contents. We also evaluated the cements in vivo by packing them into the intramedullary canals of rat tibiae. To compare the osteoconductivity of the cements, an affinity index was calculated for each cement; it equaled the length of bone in direct apposition to the cement, expressed as a percentage of the total length of the cement surface. Microradiographic examination up to 26 weeks after implantation revealed that AWC showed a higher affinity index than HAC and TCPC for each filler content although the affinity indices of all nine subgroups (especially the AWC and HAC subgroups) increased with time. New bone had formed along the AWC surface within 4 weeks, even in the cement containing AW-GC filler at only 50% (w/w); observation of the cement-bone interfaces using a scanning electron microscope showed that all the cements had directly contacted the bone. At 4 weeks the AWC had bonded to the bone via a 10 micron-thick reactive layer; the width of the layer, in which partly degraded AW-GC particles were seen, became slightly thicker with time. On the other hand, in the HAC- and TCPC-implanted tibiae, some particles on the cement surface were surrounded by new bone and partly absorbed or degraded. The results suggest that the stronger bonding between the inorganic filler and the organic matrix in the AWC cements gave them better mechanical properties. The results also indicate that the higher osteoconductivity of AWC was caused by the higher reactivity of the AW-GC powder on the cement surface., (Copyright 1999 John Wiley & Sons, Inc.)

We developed a bioactive bone cement that consists of apatite and wollastonite containing glass-ceramic (AW-GC) powder and bisphenol-a-glycidyl methacrylate (Bis-GMA) based resin. In this study, we made three types of cement (designated AWC, HAC, and TCPC) consisting of either AW-GC, hydroxyapatite (HA), or beta-tricalcium phosphate (beta-TCP) powder as the inorganic filler and Bis-GMA based resin as the organic matrix. These cements were implanted into rat tibiae and cured in situ. Specimens were prepared 1, 2, 4, and 8 weeks after the operation and observed using transmission electron microscopy. Each of the bone cements was in direct contact with the bone. In AWC-implanted tibiae, the uncured surface layer of Bis-GMA based resin was completely filled with newly formed bone-like tissue 2 weeks after implantation. The AW-GC particles were surrounded by bone and were in contact with bone through an apatite layer. No intervening soft tissue was seen. In HAC-implanted tibiae, it took 4 weeks for the uncured layer to completely fill with newly formed bonelike tissue. The HA particles were also in contact with bone through an apatite layer. In TCPC-implanted tibiae, it took 8 weeks for the uncured layer to fill with newly formed bone-like tissue. The new bone that formed on the TCPC was not as dense as that on the AWC or HAC, and an intervening apatite layer was not evident. Results indicated that AWC had higher bioactivity than either HAC or TCPC.

A study was conducted to evaluate the osteoconductivity and bone-bonding ability of two types of bioactive bone cement, both consisting of apatite and wollastonite containing glass-ceramic powder (AW-P), fused silica glass powder (SG-P), submicron fumed silica as an inorganic filler, and bisphenol-a-glycidyl methacrylate (Bis-GMA) based resin as an organic matrix. The cements had two kinds of formulas: one (dough-type cement; designated DTC) composed of 85% (w/w) filler and 15% resin, which was developed for fixation of the acetabular component in total hip arthroplasty and could be handled manually; and one (injection-type cement; designated ITC) composed of 79% (w/w) filler and 21% resin. ITC was developed for fixation of the femoral component and, because it had a lower viscosity than DTC, could be injected. The DTC and ITC both contained 73% AW-P, 25% SG-P, and 2% fumed silica in the weight ratio of the filler component. Two other types of cement, both of which consisted of 83.3% AW-P or SG-P, 1.7% fumed silica, and 15% resin, were used as reference material (designated AWC or SGC) for a detaching test. Following the packing of bone defects in the rat tibiae with either DTC or ITC, histological examination revealed that the DTC and ITC had both directly contacted the bone and were almost completely surrounded by bone by 16 weeks after the surgery and that no marked biodegradation had occurred at 52 weeks postimplantation. Rectangular plates (2 x 10 x 15 mm) of AWC, DTC, ITC, and SGC were implanted into the metaphysis of the tibia of male rabbits and the failure load was measured by a detaching test at 10 and 25 weeks after implantation. The failure loads of AWC, DTC, ITC, and SGC were 3.65, 2.21, 2.44, and 0.04 kgf at 10 weeks and 4.87, 2. 81, 2.82, and 0.13 kgf at 25 weeks, respectively. Observation of the bone-implant interface by scanning electron microscopy and energy dispersive X-ray microanalysis revealed that all the samples except SGC formed direct contact with the bone and that only AWC-implanted tibiae had a layer of a low calcium and phosphorus level at the bone-implant interface. Results showed that DTC and ITC have excellent osteoconductivity and bone-bonding ability under non-weight-bearing conditions., (Copyright 1999 John Wiley & Sons, Inc.)

Recently much attention has been paid to bioactive filler-resin composite cements because they can solidify in a few minutes to give high mechanical strengths and they can bond to living bone. In this study the dependence on resin of apatite-forming ability in simulated body fluid (SBF) was investigated for the composite cements of bioactive CaO-SiO2-P2O5-CaF2 glass with polymethyl methacrylate (PMMA) or bisphenol-a-glycidyl methacrylate/triethyleneglycol (Bis-GMA/TEGDMA) resin. The PMMA-containing composite cement did not show the apatite-forming ability in SBF because the reaction of the glass grains with SBF was inhibited due to the complete covering of the grains with PMMA. To the contrary, the Bis-GMA/TEGDMA-containing cement exhibited high apatite-forming ability in SBF; these monomers significantly dissolved from the composite surface into SBF, causing a direct exposure of the glass grains to SBF to convert into silica gel. It is assumed that thus formed silica gels, and the silicate ions that were dissolved and adsorbed onto the composite surface, induced the apatite nucleation between the spaces of the glass grains and on the composite surface, respectively. A continuous bone-like apatite layer was formed on the top surface of the glass-Bis-GMA/TEGDMA composite cement in a short period.

A study was conducted to compare the bone-bonding strengths of three types of bioactive bone cement, consisting of either apatite- and wollastonite-containing glass-ceramic (AW-GC) powder, hydroxyapatite (HA) powder, or beta-tricalcium phosphate (beta-TCP) powder as an inorganic filler and bisphenol-a-glycidyl methacrylate (Bis-GMA) based resin as an organic matrix. Seventy percent (w/w) filler was added to the cement. Rectangular plates (10 x 15 x 2 mm) of each cement were made and abraded with #2000 alumina powder. After soaking in simulated body fluid for 2 days, the AW cement (AWC) and HA cement (HAC) formed bonelike apatite over their entire surfaces, but the TCP cement (TCPC) did not. Plates of each type of cement were implanted into the tibial metaphyses of male Japanese white rabbits, and the failure loads were measured by a detaching test at 10 and 25 weeks after implantation. The failure loads of AWC, HAC, and TCPC were 3.95, 2.04, and 2.03 kgf at 10 weeks and 4.36, 3.45, and 3.10 kgf at 25 weeks, respectively. The failure loads of the AWC were significantly higher than those of the HAC and TCPC at 10 and 25 weeks. Histological examination by contact microradiogram and Giemsa surface staining of the bone-cement interface revealed that all the bioactive bone cements were in direct contact with bone. However, scanning electron microscopy and energy-dispersive X-ray microanalysis showed that only AWC had contacted to the bone via a Ca-P rich layer formed at the interface between the AW-GC powder and the bone, which might explain its high bone-bonding strength. Neither the HAC nor the TCPC contacted the bone through such a layer between each powder and the bone, although the HAC and TCPC directly contacted with bone. Our results indicate that all three types of abraded and prefabricated cement have bonding strength to bone, but AWC has superior bone-bonding strength compared to HAC and TCPC.

We introduced an inhibitor to the polymerization reaction of bioactive bone cement (AWC) consisting of MgO-CaO-SiO2-P2O5-CaF2 apatite and wollastonite containing glass-ceramic powder and bisphenol-alpha-glycidyl methacrylate based resin, together with an increased amount of accelerator but without any prolongation of its setting time in order to improve the degree of polymerization and decrease the amount of incompletely polymerized monomers on the cement surface. A comparison was made between the AWC containing the inhibitor [AWC(I+)] and the AWC without it [AWC(I-)] with regard to setting parameters, mechanical properties, and surface reactivity in vitro and in vivo. The proportion of glass-ceramic powder added to the AWC was 70% (w/w). The total amount of heat generation and the peak temperature of the AWC(I+) during polymerization were slightly greater than those of the AWC(I-). The mechanical strength of AWC(I+) was higher than that of the AWC(I-) under wet conditions. In simulated body fluid, the width of the Ca-P rich layer on the surface of the AWC(I+) was less than that on the AWC(I-) after 28 days of immersion, although the rate of apatite formation on the top surface of the AWC(I+) was almost identical to that on the AWC(I-) surface. Histological examination using rat tibiae up to 26 weeks revealed that the bioactivity of the AWC(I+) was equivalent to that of the AWC(I-). Scanning electron microscopy and energy-dispersive X-ray microanalysis demonstrated that the Ca-P rich layer in the AWC(I+) was significantly narrower than that in the AWC(I-) at the same time points. These results indicate that introduction of the inhibitor improved the mechanical properties of the AWC and made the Ca-P rich layer narrower, but it had no adverse effect on bioactivity.

We examined the influence of the proportion of glass-ceramic powder in a bioactive bone cement of our formula on the bone-bonding ability of cement. Changes in cement bonding with time also were examined. The bioactive bone cement consisted of MgO-CaO-SiO2-P2O5-CaF2 glass-ceramic powder (AW-GC powder) and bisphenol-alpha-glycidyl methacrylate (Bis-GMA)-based resin. AW-GC powder was added to the cement as 0%, 30%, 50%, 70%, and 80% w/w. Rectangular plates (2 x 10 x 15 mm) of each cement with polished surfaces were implanted into the proximal metaphysis of the tibiae of male rabbits, and the failure load was measured by detaching tests 10 and 25 weeks after implantation. The failure loads of each cement were 0% = 0.03, 30% = 1.52, 50% = 2.67, 70% = 3.56, and 80% = 5.59 kg at 10 weeks, and 0% = 0.05, 30% = 1.68, 50% = 2.77, 70% = 3.80, and 80% = 6.37 kg at 25 weeks. Observation of the cement-bone interface revealed that all bioactive bone cements (30%-80%) formed direct contact with bone whereas intervening fibrous tissue was observed in all specimens of the 0% group. By scanning electron microscopy, all bioactive bone cements (30%-80% groups) showed direct contact with bone at the cement-bone interface. In the 0% group, direct contact with bone at the cement-bone interface was not observed. By electron-probe microanalysis, a Ca-P-rich layer was not detected at the cement-bone interfaces of the 30%-70% bioactive bone cements, but in some samples of the 80% cement specimens a thin Ca-P-rich layer (3 microns thick) was observed at the interface at 10 and 25 weeks after implantation. These results show that all of the bioactive bone cements tested had the ability to bond to bone and to function as bioactive composites of ceramics and polymers.

Three types of bioactive bone cement (designated AWC, HAC, and TCPC), each consisting of bisphenol-alpha-glycidyl methacrylate (Bis-GMA)-based resin and a bioactive filler of apatite and wollastonite containing glass-ceramic (AW-GC), sintered hydroxyapatite (HA), or beta-tricalcium phosphate (beta-TCP) powder were made in order to evaluate the influence of the bioactive filler on the mechanical and biological properties of bone cement. The proportion of filler added to the cements was 70% w/w. The compressive, bending, and tensile strengths and the fracture toughness of AWC were higher than HAC and TCPC under wet conditions. The cements were evaluated in vivo by packing them into the intramedullary canals of rat tibiae. An affinity index that equalled the length of bone in direct apposition to the cement was calculated for each cement and expressed as a percentage of the total length of the cement surface. Histological examination of rat tibiae up to 8 weeks after implantation revealed that AWC had higher bioactivity than HAC and TCPC. New bone had formed along the AWC surface within 2 weeks, and at 4 weeks newly formed bone surrounded the cement surface almost completely. In HAC- and TCPC-implanted tibiae, immature bone had formed directly toward but not along the cement surface at 2 weeks. Observation of cement-bone interfaces showed that AWC had bonded to the bone via a so-called "Ca-P-rich layer"; the cement-bone interface remained stable, and the width of the CA-P-rich layer became thicker with time. On the other hand, in HAC- and TCPC-implanted tibiae, the cement surface fillers were surrounded by new bone and were absorbed gradually to become bone matrix. The cement-bone interfaces went inside the cement with time. Our results indicate that stronger interstitial bonding between the inorganic filler and the organic matrix resin in AWC lead to higher mechanical properties; results also indicate that the more stable cement-bone interface and higher bioactivity of AWC are due to early and uniform apatite formation on the cement surface.

A novel drug delivery system containing cephalexin (CEX) as a model drug using a new bioactive bone cement consisting of 15% bisphenol-alpha-glycidyl methacrylate (Bis-GMA), 15% triethylene-glycol dimethacrylate (TEGDMA) resin and 70% apatite- and wollastonite-containing glass-ceramic (A-W GC) powder was investigated. A-W GC powder containing CEX powder hardened within 5 min after mixing with Bis-GMA/TEGDMA resin, and furthermore its compressive strength was expected to be higher than that of polymethylmethacrylate cement. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 weeks. The drug release rate increased with increasing amount of CEX in the mixture. All of the drug release profiles followed the Higuchi equation at the initial stage, but not at later stages. As hydroxyapatite was precipitated out on the cement surface, the drug release rate decreased. These results suggest that the CEX release rate from bioactive bone cement could be controlled by varying the amount of drug in the cement system.

Silica glass powder (SG-P) made by a fusing-quenching method was added as a second filler to a bioactive bone cement consisting of MgO-CaO-SiO2-P2O5-CaF2 apatite and wollastonite containing glass-ceramic powder (AW-P) and bisphenol-a-glycidyl methacrylate (Bis-GMA)-based resin, to achieve a higher mechanical strength and better handling properties in use. Five types of cement were used, containing different weight ratios of AW-P/SG-P (Group 1 = 100/0; Group 2 = 75/25; Group 3 = 50/50; Group 4 = 25/75; and Group 5 = 0/100) as filler, to evaluate the effect of SG-P content on the biological, mechanical, and handling properties. The total proportion of filler added to the cements was 85% w/w. The compressive, bending, and tensile strengths and fracture toughness of the cements increased with SG-P content. The viscosity of cements also increased with SG-P content, and every cement could be handled manually. The cements were evaluated in vivo by packing the intramedullary canals of rat tibiae. An affinity index was calculated for each cement; this was the length of bone directly apposed to cement expressed as a percentage of the total length of the cement surface. Histological examination of implanted tibiae for up to 26 weeks showed that the affinity indices decreased with SG-P content and that those of all the cement groups increased with time. At 26 weeks, Groups 1 and 2 had almost identical affnity indices (79% and 75%; no significant difference) but those of the other groups remained at <50%. Group 2 had better mechanical and handling properties than Group 1, and an SG-P content in the filler of no more than 25% w/w did not interfere strongly with the bioactivity of the cement.

The bone bonding ability of three types of bioactive bone cement A, B, and C consisting of glass or glass ceramic powder and bisphenol-alpha-glycidyl methacrylate resin was evaluated. Type A contained MgO-CaO-SiO2-P2O5-CaF2 glass powder; Type B, MgO-CaO-SiO2-P2O5-CaF2 glass ceramic powder; and Type C, MgO free CaO-SiO2-P2O5-CaF2 glass powder. Rectangular plates (2 x 10 x 15 mm) of Types A, B, C, and polymethylmethacrylate cements were implanted into the tibial metaphyses of male rabbits and the failure load measured by mechanical failure testing (detaching test) 10 and 25 weeks after implantation. The failure loads of Types A, B, C, and polymethylmethacrylate cements were respectively, 29.52, 41.48, 28.22, and 0.29 N at 10 weeks and 33.42, 41.27, 33.64, and 0.20 N at 25 weeks. Examination of the bone cement interface revealed that all the bioactive bone cements achieved direct bone contact with the bone. These results showed that all three types of bioactive bone cement have the ability to bond to bone, and the cement containing glass ceramic powder revealed higher bonding strength than did those containing glass powder.

Our previous study showed that titanium metal forms a bonelike apatite layer on its surface in simulated body fluid when it was subjected to NaOH and heat treatments to form a sodium titanate hydrogel or amorphous sodium titanate surface layer. In the present study, bonding strength of the apatite layer formed on the titanium metals to the substrates were examined under tensile stress, in comparison with those of the apatite layers formed on Bioglass 45S5-type glass, dense sintered hydroxyapatite, and glass-ceramic A-W, which are already clinically used. The NaOH-treated titanium metals showed higher bonding strength of the apatite layer to the substrates, which was maximized by heat treatments at 500 and 600 degrees C, than all the examined bioactive ceramics. It is believed that bioactive metals thus obtained are useful as bone substitutes, even under load-bearing conditions.

The in vivo and in vitro drug release profiles from a self-setting bioactive CaO-SiO2-P2O5 glass bone cement containing indomethacin as a model drug were investigated. The cement containing 2% and 5% indomethacin (IMC) powder hardened within 5 min after mixing with ammonium phosphate buffer. After setting, in vitro drug release from drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for two weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite during the drug release test in SBF. An IMC-loaded cement device (2% and 5% drug) was implanted in the subcutaneous tissue on the back of rats. The in vivo IMC release from the cement increased and attained maximum levels (Cmax of 2% and 5% drug-loaded cements was 0.27 and 3.37 micrograms/ml, respectively) at Tmax, 3 and 0.5 d, respectively, upon subcutaneous (s.c.) administration in rats. This suggested that the s.c. administration of the cement provided IMC release for a much longer period than s.c. administration of the solution, and the plasma IMC concentration was dependent on the drug concentration in the cement. The plasma IMC concentration and the area under the curve from 2% and 5% IMC-loaded cements in rats were dependent on the concentration of IMC in the cements. The in vivo IMC concentration in plasma obtained by the deconvolution method was much lower than that delivered in SBF in vitro. Scanning electron microscopy and photomicrographs of cross sections showed that the bioactive bone cement had excellent biocompatibility with the surrounding soft tissues.

In this study two types of bioactive bone cement containing either MgO-CaO-SiO2-P2O5-CaF2 glass (type A) or glass-ceramic powder (type B) were made to evaluate the effect of the crystalline phases on their mechanical and biological properties. Type A bone cement was produced from glass powder and bisphenol-a-glycidyl methacrylate (BIS-GMA) resin, and type B from glass-ceramic powder containing apatite and wollastonite crystals and BIS-GMA resin. Glass or glass-ceramic powder (30, 50, 70, and 80 by wt %) was added to the cement. The compressive strength of type A (153-180 MPa) and B (167-194 MPa) cement were more than twice that of conventional polymethylmethacrylate (PMMA) cement (68 MPa). Histological examination of rat tibiae showed that all the bioactive cements formed direct contact with the bone. A reactive layer was seen at the bone-cement interface. In specimens with type A cement the reactive layer consisted of two layers, a radiopaque outer layer (Ca-P-rich layer) and a relatively radiolucent inner layer (low-calcium-level layer). With type B cement, although the Ca-P-rich layer was seen, the radiolucent inner layer was absent. Up to 26 weeks there was progressive bone formation around each cement (70 wt %) and no evidence of biodegradation. The mechanical and biological properties of the cements were compared with those of a previously reported bone cement containing MgO-free CaO-SiO2-P2O5-CaF2 glass powder (designated type C).

Silica gel has been reported to induce apatite nucleation on its surface in vitro and it can act as a stimulant that induces formation of chemical apatite (Ca-P) layers on the surfaces of bioactive glass-ceramics. In this study, apatite formation in response to and the bone-bonding behavior of silica gels implanted in the tibiae of mature rabbits were studied. Implants were made from three silica gels treated at 400, 800, and 1000 degrees C, and the effects of such heat treatment on the above parameters were investigated. The silica gel was made by hydrolysis and polycondensation of tetraethoxysilane in aqueous solution containing polyethylene glycol. Rectangular implants (15 mm x 10 mm x 2 mm) of each heat-treated silica gel were implanted into both tibial bones of mature male rabbits, which were killed 4 or 8 weeks after implantation, and the tibiae containing the implants were dissected out. The bone-implant interfaces were investigated using Giemsa surface staining, contact microradiography, scanning electron microscopy-electron probe microanalysis, and X-ray diffraction. Histologically, no bonding of bone to any of the silica gels was observed at any time postimplantation. Soft tissue was observed at the bone-silica gel interface, but there were no giant foreign body or inflammatory cells. A Ca-P-rich layer was observed only on small areas of the surfaces of the silica gels treated at 400 and 800 degrees C 4 and 8 weeks after implantation. X-ray diffraction analysis confirmed the presence of hydroxyapatite in these Ca-P-rich layers.(ABSTRACT TRUNCATED AT 250 WORDS)

A study was conducted to examine the influence of the amount of glass powder added to a bioactive bone cement of our formula on its mechanical and biologic properties. Serial changes in the cement with time were also examined. The bioactive bone cement consisted of CaO-SiO2-P2O5-CaF2 glass powder and bisphenol-a-glycidyl methacrylate resin. Glass powder was added to the cement in 30, 50, 70, and 80% weight ratios. The compressive strengths of the resulting cements (171-239 MPa) were more than double that of polymethylmethacrylate cement (68 MPa). Histologic examination of rat tibiae bearing artificial defects packed with each bioactive cement showed direct bone contact 4 weeks after surgery. The cement with a higher percentage of glass powder showed better direct formation of bone around its periphery with a thicker reactive layer. Under scanning electron microscopic observation, the reactive layer showed increased levels of calcium and phosphorus. Examination of histologic changes up to 26 weeks showed progressive bone formation around the cement and no sign of biodegradation.

A novel device consisting of Eudragit-coated cephalexin as a model drug and a self-setting bioactive cement based upon CaO-SiO2-P2O5 glass was investigated. The glass cement hardened within 5 min of mixing with a phosphate buffer. After setting, in vitro drug release from homogeneous or heterogeneous drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for over 2 weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite and decreased in volume by about 5% during drug release in SBF. Consequently, 30% of the loaded drug was initially released from the homogeneous cement system, and thereafter it was released more slowly. Since the heterogeneous system consisting of the cement and a 50% polymer coated, drug-loaded pellet avoided this drug's burst, the drug was released over a longer period than that in the homogeneous system. The heterogeneous system released the polymer-coated drug very slowly, because it completely avoided the initial burst, and sustained the release over a long period.

We have developed a bioactive bone cement consisting of silane-treated CaO-SiO 2-P 2O 5-CaF 2 glass powder as the filling particles and bisphenol-a-glycidyl methacrylate (BIS-GMA) diluted with triethylene-glycol dimethacrylate (TEGDMA) as the organic matrix. Histological examination demonstrated direct bonding between the cement and bone along the circumference of the cement at 4 weeks after implantation in rat tibia. The compressive strength and toughness of the cement were two and four times greater than those of polymethylmethacrylate (PMMA) cement, respectively. The inflammatory reaction of the skin caused by the new cement was not as intense as that for PMMA 3 days after subcutaneous implantation. This new cement may be applicable as a bioactive bone cement with high mechanical strength.

The interface between bone and a bioactive glass cement--a mixture of bioactive glass powder and ammonium phosphate solution, previously reported on by the authors--was evaluated quantitatively and histologically. The materials tested were (1) the original bioactive glass cement (BCI cement); (2) an improved type of bioactive glass cement (BCII cement); (3) polymethylmethacrylate (PMMA) bone cement; and (4) a bioactive, apatite-wollastonite-containing, glass ceramic (A-WGC). Hardened cylindrical specimens of each cement were inserted loosely into canine femora and the interfacial shear strengths were measured using a push-out test. The interfacial strength values of the bioactive glass cements increased with prolonged implantation time. At each postimplantation time studied (8, 12, and 24 weeks), the interfacial strength value of BCI cement did not differ significantly from that of A-WGC. BCII cement interfacial strength was greater than that of BCI cement, whereas the interfacial strength of PMMA bone cement remained at a very low level throughout the study. Histological examinations revealed that direct bonding of both bioactive glass cements to bone had occurred without pathologic degradation. After 24 weeks, the defects between the bone and the bioactive glass cements had been filled with mature lamellar bone. Because the bioactive glass cement system developed by the authors, especially BCII cement, shows excellent osteoconductivity and bonds to bone tightly, we consider it to be a promising material for fixing prostheses into bone.

Glass-ceramics containing crystalline oxy-fluoroapatite (Ca10(PO4)6(O,F2)) and wollastonite (CaSiO3) (designated AWGC) are reported to have a fairly high mechanical strength as well as the capability of forming a chemical bond with bone tissue. The chemical composition is MgO 4.6, CaO 44.9, SiO2 34.2, P2O5 16.3, and CaF2 0.5 in weight ratio. In this study the influence of substituting B2O3 for CaF2 on the bonding behaviour of glass-ceramics containing apatite and wollastonite to bone tissue was investigated. Two kinds of glass-ceramics containing apatite and wollastonite were prepared. CaF2 0.5 was replaced with B2O3 at 0.5 and 2.0 in weight ratio (designated AWGC-0.5B and AWGC-2.0B). Rectangular ceramic plates (15 x 10 x 2 mm, abraded with No. 2000 alumina powder) were implanted into a rabbit tibia. The failure load, when an implant detached from the bone, or the bone itself broke, was measured. The failure load of AWGC-0.5B was 8.00 +/- 1.82 kg at 10 weeks after implantation and 8.16 +/- 1.36 kg at 25 weeks after implantation. The failure load of AWGC-2B was 8.08 +/- 1.70 kg at 10 weeks after implantation and 9.92 +/- 2.46 kg at 25 weeks after implantation. None of the loads for the two kinds of glass-ceramics decreased as time passed. Giemsa surface staining and contact microradiography revealed direct bonding between glass-ceramics and bone. SEM-EPMA showed a calcium-phosphorus rich layer (reaction zone) at the interface of ceramics and bone tissue. The thickness of the reaction zone was 10 to -15 microns and did not increase as time passed.(ABSTRACT TRUNCATED AT 250 WORDS)

We have developed a bioactive bone cement using CaO-SiO 2-P 2O 5-CaF 2 glass powders and ammonium phosphate solution, and investigated its histological and mechanical characteristics in vivo. A bone defect was drilled in proximal metaphysis of the rat tibia and filled with the bioactive bone cement in paste form or polymethylmethacrylate (PMMA) bone cement in the dough state. The cements were allowed to harden in situ. Histological examination demonstrated direct bonding between the new cement and bone by 4 weeks. The bioactive bone cement did not degrade up to 24 weeks postimplantation. The inflammatory reaction to the bioactive bone cement was less intense than the reaction induced by PMMA. Changes in the mechanical properties of the cement in vivo were studied by implanting hardened cylindrical specimens of both types of cement into the hindlimb muscles of rats for 12 weeks. The compressive strength of the bioactive cement increased significantly after implantation, and reached 68 MPa in 1 week and 73 MPa in 4 weeks. These values were comparable to those of PMMA, and were maintained up to 12 weeks after implantation. This bioactive bone cement hardens in situ within a few minutes with negligible rise of temperature and can be easily handled as a paste for filling bone cavities of different shapes. In addition, this cement has good osteoconductive and bone bonding potential and fairly high mechanical strength. Therefore, this new cement could be used both as a bioactive bone cement and bone defect filler.

It has been proposed that the formation of a surface apatite layer in vivo on surface active ceramics is an essential condition for chemical bonding between ceramics and bone tissue. To clarify the difference in bone-bonding mechanisms between surface active ceramics and bioresorbable ceramics, two experiments were performed using plates of dense beta-tricalcium phosphate (beta-TCP). First, plates of beta-TCP were implanted subcutaneously in rats for 8 weeks. Surface change due to bioresorption was observed with scanning electron microscopy. Formation of the apatite layer on the surface was investigated using thin-film x-ray diffraction and Fourier transform infrared reflection spectroscopy. Second, plates of beta-TCP were implanted in tibiae of rabbits for 8 and 25 weeks and subjected to the detaching test to measure bone-bonding strength. beta-TCP bonded strongly to bone. Undecalcified sections of the interface of bone and beta-TCP were examined with SEM-EPMA. However, by physicochemical methods, no formation of surface apatite layer was observed. These results suggest that beta-TCP bonds to bone through microanchoring between bone and rough surface of resorbed beta-TCP.

Glass plates of the chemical composition: CaO (29.0), SiO 2 (31.0), Fe 2O 3 (40.0), B 2O 3 (3.0), P 2O 5 (3.0) in weight ratio were heated to 1050 degrees C at a rate of 5 degrees C/min and then cooled to laboratory temperature. The resulting glass-ceramic containing magnetite and wollastonite crystals showed high-saturation magnetization. The bonding ability of this new glass-ceramic to bone tissue was evaluated using rabbit tibiae, and compared with glass of the same composition. This glass-ceramic formed a Ca, P-rich layer on its surface and bonded tightly with bone within 8 weeks of implantation. However, the glass did not form this Ca, P-rich layer, nor had it bonded with bone at 25 weeks. The bone-heating ability of this glass-ceramic was investigated by applying a max. 300-Oe, 100-kHz magnetic field. The granules of the glass-ceramic filled in the rabbit tibiae heated the whole surrounding bone to more than 42 degrees C and maintained this temperature for 30 min. Bioactive ceramics reinforce the mechanical strength of bone tissue. Furthermore, this heat-generating bioactive glass-ceramic can be used for hyperthermic treatment of bone tumors.

Bioactive glass powder (AW-G) was made into a rigid compound by mixing with ammonium hydrogen phosphate and was evaluated as a bone-defect filler. The proximal metaphysis of the rat tibia was drilled and packed with (a) polymethyl-methacrylate (PMMA) bone cement, (b) AW-G powder, (c) AW-G powder with ammonium hydrogen phosphate (AW-G)-(A-P), or (d) nothing, as a control. The animals, with different implantation periods up to 24 weeks, were sacrificed and the defective sites were histologically analyzed. The results revealed direct bonding between the bone tissue and the (AW-G)-(A-P). The general inflammatory reaction of (AW-G)-(A-P) was less than that of PMMA bone cement. The compressive strength of (AW-G)-(A-P) implanted subcutaneously into rats was measured chronologically and deterioration did not occur during a period of 24 weeks. The rigidity increased to 1.6 times 6 months after implantation as compared with the initial value. This compound can be used as paste and is transformed into a rigid compound in about 4 min without noticeable elevation of the temperature. Thus, this (AW-G)-(A-P) composite can be used as a bone defect filler, and there is a possibility that it can even be used as a bone cement if higher rigidity can be attained.

In this study, it was found that a Ca-P layer and a Si layer were formed on the interface of the mother glass of apatite-wollastonite containing glass-ceramics (designated AW) and bone tissue. The dissolution of Si, Ca, and P from glass (MgO-CaO-SiO2-P2O5-CaF2) is necessary to form a chemical film (a Si layer and a Ca-P layer). The three kinds of glasses used were 1) a mirror surface of the mother glass (MgO 4.6, CaO 44.9, SiO2 34.2, P2O5 16.3, CaF 0.5 weight ratio) of AW (designated G-AW (mirror], 2) an abraded surface of G-AW (designated G-AW (#2000)), 3) a mirror surface SiO2 glass (designated G-Si, 100% SiO2). The glass plates (15 mm x 10 mm x 2 mm) were implanted into the metaphysis of tibia of mature male rabbits for 10 and 25 weeks. The failure load, when an implant detached from the bone or when the bone itself broke, was measured by a detaching test and the interface of glass/bone was observed by SEM-EPMA. Failure loads in G-Si, G-AW (mirror), and G-AW (#2000) 10 weeks after implantation were 0.18 +/- 0.24, 3.06 +/- 1.29, and 2.94 +/- 1.77 kg, respectively. Those in G-Si, G-AW (mirror), and G-AW (#2000) 25 weeks after implantation were 1.30 +/- 1.18, 3.88 +/- 1.06, and 3.55 +/- 1.51, respectively. The failure loads in G-Si vs. G-AW (mirror) and those in G-Si vs. G-AW (#2000) differed significantly (P less than 0.01). There were no significant differences in the failure load according to the surface roughness of G-AW. As shown by SEM-EPMA observation, a Si layer next to G was adjacent to a Ca-P layer next to the bone. The chemical film showed no increase in thickness as time passed. A Ca-P layer did not form on the interface of Si-G and bone.