Alumina powder/Bis-GMA composite: effect of filler content on mechanical properties and osteoconductivity

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.     

PMMA-based bioactive cement: effect of CaF2 on osteoconductivity and histological change with time

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.     

Mechanical properties and osteoconductivity of new bioactive composites consisting of partially crystallized glass beads and poly(methyl methacrylate)

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.     

Bone-bonding behavior of alumina bead composite.

Previously we developed an alumina bead composite (ABC) consisting of alumina bead powder (AL-P) and bisphenol-alpha-glycidyl methacrylate (Bis-GMA)-based resin and reported its excellent osteoconductivity in rat tibiae. In the present study, are evaluated histologically and mechanically the effect of alumina crystallinity on the osteoconductivity and bone-bonding strength of the composite. AL-P was manufactured by fusing crushed alpha-alumina powder and quenching it. The AL-P was composed mainly of amorphous and delta-crystal phases of alumina. Its average particle size was 3.5 microm, and it took a spherical form. Another composite (alpha ALC), filled with pure alpha-alumina powder (alpha AL-P), was used as a referential material. The proportion of powder added to each composite was 70% w/w. Mechanical testing of ABC and alpha ALC indicated that they would be strong enough for use under weight-bearing conditions. The affinity indices for ABC, determined using male Wistar rat tibiae, were significantly higher than those for alpha ALC (p < 0.0001) up to 8 weeks. Composite plates (15 x 10 x 2 mm) that had an uncured surface layer on one side were made in situ in a rectangular mold. One of the plates was implanted into the proximal metaphysis of the tibia of a male Japanese white rabbit, and the failure load was measured by a detaching test 10 weeks after implantation. The failure loads for ABC on its uncured surface [1.91+/-1.23 kgf (n = 8)] were significantly higher than those for alpha ALC on its uncured surface [0.35+/-0.33 kgf (n = 8); (p < 0.0001)], and they also were significantly higher than those for ABC on the other (cured surface) side (p < 0.0001). Histological examinations using rabbit tibiae revealed bone ingrowth into the composite only on the uncured surface of ABC. This study revealed that the amorphous phase of alumina and formation of an uncured surface layer are needed for the osteoconductive and bone-bonding ability of ABC. ABC shows promise as a basis for the development of a highly osteoconductive and mechanically strong biomaterial.     

Effects of apatite and wollastonite containing glass-ceramic powder and two types of alumina powder in composites on osteoblastic differentiation of bone marrow cells

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.     

Ultrastructure of the interface between alumina bead composite and bone

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.     

The biocompatibility and osteoconductivity of a cement containing beta-TCP for use in vertebroplasty

A new composite bone cement designated "G2B1" was developed for percutaneous transpedicular vertebroplasty. G2B1 contains beta tricalcium phosphate particles and methylmethacrylate-methylacrylate copolymer as the powder components, and methylmethacrylate, urethane dimethacrylate, and tetrahydrofurfuryl methacrylate as the liquid components. Biocompatibility and osteoconductivity were evaluated using scanning electron microscopy, contact microradiography, and Giemsa surface staining 4, 8, 12, 26, and 52 weeks after implantation into rat tibiae. To evaluate osteoconductivity, affinity indices (%) were calculated. Scanning electron microscopy and contact microradiography revealed that bone contact with G2B1 was attained within 4 weeks (affinity index: 50.2 +/- 11.8 at 4 weeks) and at most of the margin within 26 weeks (affinity index: 87.4 +/- 7.2 at 26 weeks). Specifically, G2B1 contacted bone via a wide calcium-phosphate-rich layer, and its degradation started within 8 weeks, mainly in the marginal area. Giemsa surface staining showed that there was almost no inflammatory reaction around the G2B1. These results indicate that G2B1 is a biocompatible and osteoconductive bone cement.     

Bioactive polymethyl methacrylate-based bone cement: comparison of glass beads, apatite- and wollastonite-containing glass-ceramic, and hydroxyapatite fillers on mechanical and biological properties

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.     

Bioactive bone cement: Effect of silane treatment on mechanical properties and osteoconductivity

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.     

Histomorphometric study on high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures

The purpose of this study was to investigate the bone-implant interface of high-strength hydroxyapatite (HA)/poly(L-lactide) (PLLA) composite rods. As reinforcing particles, two types of HA particles-calcined HA (c-HA) and uncalcined HA (u-HA)-were applied to allow comparison of their suitability as bioactive fillers. Four types of composites (c-HA30, c-HA40, u-HA30, and u-HA40), which contained 30 or 40% by weight of each HA particle, were used. Unfilled PLLA rods were used as controls. A hole was drilled in the distal femora of 50 rabbits, and a composite or unfilled PLLA rod was implanted in a press-fit manner. Two, 4, 8, and 25 weeks after implantation, the samples were examined histologically by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). An image analyzer was used for histomorphometric analysis of the bone-implant interface. An affinity index was calculated for each material; this was the length of bone directly apposed to the rods expressed as a percentage of the total length of the rod surface. In all the composites, histologic examination showed new bone formation at 2 weeks after implantation. The bone gradually grew along the composite surface. SEM showed direct bone contact with the composites without intervening fibrous tissue. During follow-up, the affinity indices of all the composite rods were significantly higher than those of the unfilled PLLA rods (p < 0.01; two-way ANOVA). The maximum affinity index (41%) was attained at 4 weeks in c-HA40 rods. In contrast, little bone contact was seen in unfilled PLLA rods. The only significant difference in affinity indices among the composites was that c-HA40 had a higher affinity index than u-HA40 (p < 0.05 at 4 weeks). No disintegration of rods or polymer debris, which could elicit inflammatory tissue reactions, was observed even at 25 weeks. Our results indicate that osteoconductive bone formation on composites could enhance the stability between bone and implant in fracture repair.     

Bioactive bone cement: effects of phosphoric ester monomer on mechanical properties and osteoconductivity

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.     

A new bioactive bone cement: effect of glass bead filler content on mechanical and biological properties.

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.     

Bioactive bone cement: effect of filler size on mechanical properties and osteoconductivity

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.     

Effect of bioactive filler content on mechanical properties and osteoconductivity of bioactive bone cement.

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.     

PMMA-based bioactive cement: effect of glass bead filler content and histological change with time.

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.     

A 12 month in vivo study on the response of bone to a hydroxyapatite-polymethylmethacrylate cranioplasty composite

We investigated the osteoconductivity and biocompatibility in vivo of a new hydroxyapatite-polymethylmethacrylate (HA-PMMA) composite developed for use as an implant material for cranioplasty, which is expected to have the good osteoconductivity of HA together with the strength and ease of handling of PMMA. The HA-PMMA composites were implanted in eight full-grown beagles and then 6, 12, 24 weeks and 1 year after implantation, the animals were sacrificed and the implanted materials removed along with the surrounding tissues. Extirpated specimens were studied using an optical microscope and micro-computed tomography (micro-CT). Fibrous connective tissue was prominent in the interface of the composite at 6 weeks. New bone formation was seen around the implant, 12 and 24 weeks after operation. At 1 year, new bone filled in the interface of the HA-PMMA composite and adhered to the surrounding autogenous bone. Mixing HA and PMMA did not interfere with the osteoconductivity of the HA component. In micro-CT findings, the new bone growing on the HA-PMMA composite could be seen attaching preferentially to HA particles exposed at the composite surface, rather than the PMMA. This study demonstrated that this HA-PMMA composite is a good candidate for cranial bone implants due to its good osteoconductivity and biocompatibility.     

Evaluation of cytocompatibility and bending modulus of nanoceramic/polymer composites

In an attempt to simulate the microstructure and mechanical properties of natural bone, novel nanoceramic/polymer composite formulations were fabricated and characterized with respect to their cytocompatibility and mechanical properties. The bending moduli of nanocomposite samples of either poly(L-lactic acid) (PLA) or poly(methyl methacrylate) (PMMA) with 30, 40, and 50 wt % of nanophase (<100 nm) alumina, hydroxyapatite, or titania loadings were significantly (p < 0.05) greater than those of pertinent composite formulations with conventional, coarser grained ceramics. The nanocomposite bending moduli were 1-2 orders of magnitude larger than those of the homogeneous, respective polymer. For example, compared with 0.06 GPa for the 100% PLA, the bending modulus of 50/50 nanophase alumina/PLA composites was 3.5 GPa. Osteoblast adhesion on the surfaces of the nanophase alumina/PLA composites increased as a function of the nanophase ceramic content. Most importantly, osteoblast adhesion on the 50/50 nanophase alumina/PLA substrates was similar to that observed on the 100% nanophase ceramic substrates. Similar trends of osteoblast adhesion were observed on the surfaces of the nanophase titania/polymer and nanophase hydroxyapaptite/polymer composites that were tested. In contrast, fibroblast adhesion on the nanophase composites was either similar or lower than that observed on the conventional composites with either PLA or PMMA and minimum on all tested neat nanophase substrates. The calcium content in the extracellular matrix of cultured osteoblasts was also enhanced on the nanoceramic/PLA composite substrates tested as a function of the nanophase ceramic loading and duration of cell culture. The results of the present in vitro study provide evidence that nanoceramic/polymer composite formulations are promising alternatives to conventional materials because they can potentially be designed to match the chemical, structural, and mechanical properties of bone tissue in order to overcome the limitations of the biomaterials currently used as bone prostheses.     

Mechanical properties and biological behavior of carbon nanotube/polycarbosilane composites for implant materials

Multiwalled carbon nanotube/polycarbosilane (MWCNT/PCS) composites were fabricated by the spark plasma sintering (SPS) method. The MWCNT/PCS composites consisted of MWCNTs and nanosized SiC particles pyrolyzed from PCS and possessing good mechanical properties for bone tissue repair or dental implantation. The MWCNT/PCS composites were implanted in the subcutaneous tissue and femur of rats at 1 and 4 weeks after implantation. Histological investigations showed that there was little inflammatory response in the subcutaneous tissue, and newly formed bone tissue was observed in the femur. These results indicated that the MWCNT/PCS composite had little prophlogistic effect and good osteoconductivity. The study suggested the possibility that the MWCNT/PCS composite could be a candidate bone-substitute and dental-implant material in the future.     

Ultrastructure of the interface between bioactive composite and bone: comparison of apatite and wollastonite containing glass-ceramic filler with hydroxyapatite and beta-tricalcium phosphate fillers.

We have developed a bioactive bone cement that consists of apatite and wollastonite containing glass-ceramic (AW-GC) powder and bisphenol-a-glycidyl dimethacrylate (Bis-GMA)-based resin. In this study, we made three types of composite (designated AWC, HAC, and TCPC) consisting of AW-GC, hydroxyapatite (HA,) or beta-tricalcium phosphate (beta-TCP) powder as the inorganic filler and Bis-GMA-based resin as the organic matrix. The proportion by weight of the filler mixed into the cement was 70%. Rectangular plates (10 x 15 x 2 mm) of each composite were made and abraded with 2000 alumina powder. These composites were implanted into tibial metaphyses of rabbits. Specimens were prepared 10 and 25 weeks after implantation and examined using transmission electron microscopy (TEM). AWC was in direct contact with bone 10 weeks after implantation, and AW-GC particles were partially absorbed at the surface. HAC was in contact with partially mineralized extracellular matrix 10 weeks after implantation. In TCPC-implanted specimens, randomly oriented mineral was observed 10 weeks after implantation; however, collagenous extracellular matrix rarely was observed. In 25-week specimens, AW-GC particles were completely absorbed and replaced by new bone, and there was no intervening soft tissue. Both HAC and TCPC were in contact with bone at 25 weeks. These results indicate that AWC has higher bioactivity than either HAC or TCPC.     

The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration

Osteogenic agents, such as bone morphogenetic protein-2 (BMP-2), can stimulate the degradation as well as the formation of bone. Hence, they could impair the osteoconductivity of functionalized implant surfaces. We assessed the effects of BMP-2 and its mode of delivery on the osteoconductivity of dental implants with either a naked titanium surface or a calcium-phosphate-coated one. The naked titanium surface bore adsorbed BMP-2, whilst the coated one bore incorporated, adsorbed, or incorporated and adsorbed BMP-2. The implants were inserted into the maxillae of adult miniature pigs. The volume of bone deposited within a defined "osteoconductive" (peri-implant) space, and bone coverage of the implant surface delimiting this space, were estimated morphometrically 1-3 weeks later. After 3 weeks, the volume of bone deposited within the osteoconductive space was highest for coated and uncoated implants bearing no BMP-2, followed by coated implants bearing incorporated BMP-2; it was lowest for coated implants bearing only adsorbed BMP-2. Bone-interface coverage was highest for coated implants bearing no BMP-2, followed by coated implants bearing either incorporated, or incorporated and adsorbed BMP-2; it was lowest for uncoated implants bearing adsorbed BMP-2. Hence, the osteoconductivity of implant surfaces can be significantly modulated by BMP-2 and its mode of delivery.