PMMA-based bone cements containing magnetite particles for the hyperthermia of cancer.

Polymethylmethacrylate-based cements containing magnetite (Fe(3)O(4)) particles were prepared and their structure and properties were investigated. The Fe(3)O(4) particles were uniformly dispersed in the cement matrix and constituted a maximum of 60 wt.% of the total weight of cement. The setting time of the cement increased and the maximum temperature during the setting reaction decreased with increasing Fe(3)O(4) content. The compressive strength of cement increased with increasing Fe(3)O(4) content. Cement with 50 wt.% Fe(3)O(4) particles generated heat in alternating magnetic fields of 300 and 120 Oe at a frequency of 100 kHz.

Preparation of bioactive titania films on titanium metal via anodic oxidation.

OBJECTIVES: To research the crystal structure and surface morphology of anodic films on titanium metal in different electrolytes under various electrochemical conditions and investigate the effect of the crystal structure of the oxide films on apatite-forming ability in simulated body fluid (SBF). METHODS: Titanium oxide films were prepared using an anodic oxidation method on the surface of titanium metal in four different electrolytes: sulfuric acid, acetic acid, phosphoric acid and sodium sulfate solutions with different voltages for 1 min at room temperature. RESULTS: Anodic films that consisted of rutile and/or anatase phases with porous structures were formed on titanium metal after anodizing in H(2)SO(4) and Na(2)SO(4) electrolytes, while amorphous titania films were produced after anodizing in CH(3)COOH and H(3)PO(4) electrolytes. Titanium metal with the anatase and/or rutile crystal structure films showed excellent apatite-forming ability and produced a compact apatite layer covering all the surface of titanium after soaking in SBF for 7d, but titanium metal with amorphous titania layers was not able to induce apatite formation. SIGNIFICANCE: The resultant apatite layer formed on titanium metal in SBF could enhance the bonding strength between living tissue and the implant. Anodic oxidation is believed to be an effective method for preparing bioactive titanium metal as an artificial bone substitute even under load-bearing conditions.

Induction of bioactivity on silicone elastomer by simultaneous irradiation of oxygen cluster and monomer ion beams.

Silicone elastomer substrates were irradiated with acceleration voltages ranging from 3 to 9 kV and doses ranging from 1 x 10(14) to 2.5 x 10(15) ions cm(-2) by the simultaneous use of oxygen cluster and monomer (O(2) CM) ion beams, and then soaking in CaCl(2) solution. The apatite-forming ability of the substrates was examined using a metastable calcium phosphate solution that had 1.5 times the ion concentrations of normal simulated body fluid (1.5SBF). Silicon oxide clusters (SiO(x)) were formed at the silicone elastomer surfaces and the hydrophilicity of the substrates was remarkably improved by the irradiation. The irradiated silicone elastomer substrates formed apatite in 1.5SBF, whereas unirradiated ones did not. These results suggest that irradiation using O(2) CM ion beams is effective for inducing an apatite-forming ability on silicone elastomer substrates.

Growth of a bonelike apatite on chitosan microparticles after a calcium silicate treatment.

Bioactive chitosan microparticles can be prepared successfully by treating them with a calcium silicate solution and then subsequently soaking them in simulated body fluid (SBF). Such a combination enables the development of bioactive microparticles that can be used for several applications in the medical field, including injectable biomaterial systems and tissue engineering carrier systems. Chitosan microparticles, 0.6microm in average size, were soaked either for 12h in fresh calcium silicate solution (condition I) or for 1h in calcium silicate solution that had been aged for 24h before use (condition II). Afterwards, they were dried in air at 60 degrees C for 24h. The samples were then soaked in SBF for 1, 3 and 7 days. After the condition I calcium silicate treatment and the subsequent soaking in SBF, the microparticles formed a dense apatite layer after only 7 days of immersion, which is believed to be due to the formation of silanol (Si-OH) groups effective for apatite formation. For condition II, the microparticles successfully formed an apatite layer on their surfaces in SBF within only 1 day of immersion.

Functionalization of different polymers with sulfonic groups as a way to coat them with a biomimetic apatite layer.

Covalent coupling of sulfonic group (-SO 3H) was attempted on different polymers to evaluate efficacy of this functional group in inducing nucleation of apatite in body environment, and thereupon to design a simple biomimetic process for preparing bonelike apatite-polymer composites. Substrates of polyethylene terephthalate (PET), polycaprolactam (Nylon 6), high molecular weight polyethylene (HMWPE) and ethylene-vinyl alcohol co-polymer (EVOH) were subjected to sulfonation by being soaked in sulfuric acid (H2SO4) or chlorosulfonic acid (ClSO 3H) with different concentrations. In order to incorporate calcium ions, the sulfonated substrates were soaked in saturated solution of calcium hydroxide (Ca(OH)2). The treated substrates were soaked in a simulated body fluid (SBF). Fourier transformed infrared spectroscopy, thin-film X-ray diffraction, and scanning electron microscopy showed that the sulfonation and subsequent Ca(OH)2 treatments allowed formation of -SO3H groups binding Ca2+ ions on the surface of HMWPE and EVOH, but not on PET and Nylon 6. The HMWPE and EVOH could thus form bonelike apatite layer on their surfaces in SBF within 7 d. These results indicate that the -SO3H groups are effective for inducing apatite nucleation, and thereby that surface sulfonation of polymers are effective pre-treatment method for preparing biomimetic apatite on their surfaces.

Surface structure and apatite-forming ability of polyethylene substrates irradiated by oxygen cluster ion beams.

Polyethylene (PE) substrates were irradiated at a dose of 1 x 10(15) ions/cm(2) by the simultaneous use of oxygen (O(2)) cluster and monomer ion beams. The acceleration voltage for the ion beams was varied from 3 to 9 kV. Unirradiated and irradiated PE substrates were soaked for 7 days in a metastable calcium phosphate solution (1.5SBF) that had 1.5 times the ion concentrations of a normal simulated body fluid. The irradiated PE substrates formed apatite on their surfaces, irrespective of the acceleration voltage, whereas unirradiated substrates did not form apatite. This is attributed to the formation of functional groups that are effective for apatite nucleation, such as --COOH groups, on the substrate surface by the simultaneous use of O(2) cluster and monomer ion beams. The apatite-forming ability of the irradiated PE substrates was improved greatly by a subsequent CaCl(2) solution treatment. This suggests that Ca(2+) ions introduced on the substrate surface by the CaCl(2) solution treatment accelerated the apatite nucleation. It is concluded that apatite-forming ability can be induced on the surface of PE by the simultaneous use of O(2) cluster and monomer ion beams.

Surface modification of organic polymers with bioactive titanium oxide without the aid of a silane-coupling agent.

Polyethylene (PE), polyethylene terephthalate (PET), ethylene-vinyl alcohol copolymer (EVOH), and poly(epsilon-caprolactam) (Nylon 6) were successfully modified with a thin crystalline titanium oxide layer on their surfaces by a simple dipping into a titanium alkoxide solution and a subsequent soak in hot HCl solution, without the aid of a silane-coupling agent. The surface modified polymers formed a bone-like apatite layer in a simulated body fluid (SBF) within a period of 2 days. PE, PET, and Nylon 6 formed an apatite layer faster and had a higher adhesive strength to the apatite. Three-dimensional fabrics with open spaces in various sizes containing such surface modified polymer fibers are expected to be useful as bone substitutes, since they may be able to form apatite on their constituent fibers in the living body, and thus, integrate with living bone.

Alkaline treatments to render starch-based biodegradable polymers self-mineralizable.

The present research aims to develop a new route for surface functionalization of biodegradable polymers. The method is based on a wet chemistry modification, resulting in etching and/or hydrolysis in order to increase the amount of polar groups, such as hydroxyl (--OH) and carboxylic (--COOH) groups on the surface of the polymer. The polymer used as substrate was a corn starch-ethylene vinyl alcohol biodegradable blend (SEVA-C). For that purpose it was used in two different types of activation: (a) calcium hydroxide solution [Ca(OH)(2)] and (b) sodium hydroxide solution (NaOH). These treatments lead to the formation carboxylic acid-rich SEVA-C surfaces. Then, the samples were soaked in simulated body fluid (SBF) for different time periods of time until 7 days. After 1 day in SBF, the surface of SEVA-C was fully covered with spherulite particles. As the soaking time increased, the particles increased and coalesced, leading to the formation of a dense and uniform layer. Furthermore, thin-film X-ray diffraction confirms that the layer formed on the surface of the polymer was an apatite-like layer. These results suggest that this rather simple treatment is a good method for surface functionalization and subsequent mineral nucleation and growth on biodegradable polymeric surfaces to be used for bone-related applications.

Bioactive bone cements containing nano-sized titania particles for use as bone substitutes.

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.

Apatite-forming ability of alginate fibers treated with calcium hydroxide solution.

Calcium alginate fibers were prepared by extruding an aqueous sodium alginate solution into an aqueous calcium chloride solution. The fibers were treated with a saturated aqueous calcium hydroxide solution for various periods and their apatite-forming ability was examined in a simulated body fluid (SBF). The calcium alginate fibers were treated with the aqueous calcium hydroxide solution for periods longer than five days formed apatite on their surfaces in SBF, and their apatite-forming ability improved with increasing calcium hydroxide treatment time. The amount of calcium ions released from the fibers also increased with increasing calcium hydroxide treatment time, resulting in acceleration of nucleation and growth of apatite on the fiber surfaces. The resultant apatite-alginate fiber composite is expected to be useful as a flexible bioactive bone-repairing material.

Bioactive metals: preparation and properties.

Some ceramics, such as Bioglass, sintered hydroxyapatite, and glass-ceramic A-W, spontaneously form a bone-like apatite layer on their surface in the living body, and bond to bone through the apatite layer. These materials are called bioactive ceramics, and are clinically important for use as bone-repairing materials. However, they cannot be used at high-load sites, such as is found in femoral and tibial bones, because their fracture toughness values are not as high as that of human cortical bone. Titanium metal and its alloys have high fracture toughness, and form a sodium titanate layer on its surface when soaked in a 5 M-NaOH solution at 60 degrees C for 24 h, followed by a heat treatment at 600 degrees C for 1 h. On moving toward the metal interior, the sodium titanate layer gradually changes into the pure metal within a distance of 1 microm from the surface. The mechanical strength of the titanium metal or a titanium alloy is not adversely affected by these chemical and thermal treatments. The titanium metal and its alloys resulting from the above treatment can release Na+ ions from its surface into a surrounding body fluid via an ion exchange reaction with H3O+ ions, resulting in many Ti-OH groups forming on its surface. These Ti-OH groups initially combine with Ca2+ ions to form amorphous calcium titanate in the body environment, and later the calcium titanate combines with phosphate ions to form amorphous calcium phosphate. The amorphous calcium phosphate eventually transforms into bone-like apatite, and by this process the titanium metals are soon tightly bonded to the surrounding living bone through the bone-like apatite layer. The treated metals have already been subjected to clinical trials for applications in artificial total hip joints. Metallic tantalum has also been found to bond to living bone after it has been subjected to the NaOH and heat treatment to form a sodium tantalate layer on its surface.

The mechanism of biomineralization of bone-like apatite on synthetic hydroxyapatite: an in vitro assessment.

The mechanism of biomineralization of bone-like apatite on synthetic hydroxyapatite (HA) has been investigated in vitro, in which the HA surface was surveyed as a function of soaking time in simulated body fluid (SBF). In terms of surface structure by transmission electron microscopy with energy-dispersive X-ray spectrometry, the HA whose Ca/P atomic ratio was 1.67 revealed three different characteristic soaking periods in SBF, i.e. the first soaking period, in which the HA surface increased the Ca/P ratio up to 1.83 to form an amorphous phase of Ca-rich calcium phosphate; the second soaking period, in which the HA surface decreased the Ca/P ratio up to 1.47 to form an amorphous phase of Ca-poor calcium phosphate; and the third soaking period, in which the HA surface gradually increased the Ca/P ratio up to 1.65 to eventually produce the bone-like nano-cerystallites of apatite, which grew forming complex crystal assemblies with a further increase in immersion time. Analysis using electrophoresis spectroscopy indicated that, immediately after immersion in SBF, the HA revealed a highly negative surface potential, which increased to reach a maximum positive value in the first soaking period. The surface potential then decreased to again reach a negative value in the second soaking period and thereafter converge to a constant negative value in the third soaking period. This implies that the HA induces biomineralization of apatite by smartly varying its surface potential to trigger an electrostatic interaction, first with positive calcium ions and second with negative phosphate ions in the SBF.

Mechanical properties of glass-ceramic A-W-polyethylene composites: effect of filler content and particle size.

Composites which comprise a bioactive filler and ductile polymer matrix are desirable as implant materials since both their biological and mechanical properties can be tailored for a given application. In the present study three-point bending was used to characterise biomedical materials composed of glass-ceramic apatite-wollastonite (A-W) particulate reinforced polyethylene (PE) (denoted as AWPEX). The effects of filler volume fraction, varied from 10 to 50 vol%, and average particle size, 4.4 and 6.7 microm, on the bending strength, yield strength, mode of fracture, Young's modulus and strain to failure were investigated. HAPEX, a commercially used composite of hydroxyapatite and polyethylene, with a 40 vol% filler content, was used for comparison. Increasing the filler content caused an increase in Young's modulus, yield strength and bending strength, and a decreased strain to failure. When filler particle size was increased, the Young's modulus, yield and bending strengths were found to be slightly reduced. A transition in fracture behaviour from ductile to brittle behaviour was observed in samples containing between 30 and 40 vol% filler.

Bonding strength of the apatite layer formed on glass-ceramic apatite-wollastonite-polyethylene composites.

Bioactive glass-ceramic apatite-wollastonite (A-W) has been incorporated into polyethylene in particulate form to create new bioactive composites for potential maxillofacial applications. The effects of varying the volume fraction of glass-ceramic A-W filler and the glass-ceramic A-W particle size were investigated by measuring the bonding strength of the bonelike apatite layer formed on the surface of glass-ceramic A-W-polyethylene composites. The bonding strength was evaluated via a modified ASTM C-333 standard in which a tensile stress was applied to the substrate and the strength of the bioactive layer was compared with that formed on commercially available hydroxyapatite-polyethylene composite samples, HAPEX. The composites demonstrated greater bonding strength with increased filler content and reduced filler particle size (maximum 6.9 +/- 0.5 MPa) and a marginally greater bonding strength as compared with HAPEX (2.8 +/- 0.5 MPa), when glass-ceramic A-W-polyethylene composite samples with the same filler content were tested. The higher bonding strength of the apatite layer formed on the A-W-polyethylene composite samples suggests that, in addition to maxillofacial applications, these composites might also be utilized in applications involving higher levels of load bearing.

Apatite-forming ability of carboxyl group-containing polymer gels in a simulated body fluid.

Carboxymethylated chitin, gellan gum, and curdlan gels were soaked in a simulated body fluid (SBF) having ion concentrations nearly equal to those of human blood plasma. Some of the gels had been soaked in a saturated Ca(OH)(2) solution, while others had not. The carboxymethylated chitin and gellan gum gels have carboxyl groups, while the curdlan gel has hydroxyl groups. None of the gels formed apatite on their surfaces in the SBF when they had not been subjected to the Ca(OH)(2) treatment, whereas the carboxymethylated chitin and gellan gum gels formed apatite on their surfaces when they had been subjected to the Ca(OH)(2) treatment. The curdlan gel did not form an apatite deposit even after the Ca(OH)(2) treatment. Apatite formation on the carboxymethylated chitin and gellan gum gels was attributed to the catalytic effect of their carboxyl groups for apatite nucleation, and acceleration of apatite nucleation from released Ca(2+) ions. This result provides a guiding principle for obtaining apatite-organic polymer fiber composites. This composite is expected to have an analogous structure to that of natural bone.

Apatite-forming ability of glass-ceramic apatite-wollastonite - polyethylene composites: effect of filler content.

The bioactivity of a range of glass-ceramic apatite-wollastonite (A-W) - polyethylene composites (AWPEXs) with glass-ceramic A-W volume percentages ranging from 10 to 50, has been investigated in an acellular simulated body fluid (SBF) with ion concentrations similar to those of human blood plasma. The formation of a biologically active apatite layer on the composite surface after immersion in SBF was demonstrated by thin-film X-ray diffraction (TF-XRD) and field-emission scanning electron microscopy (FE-SEM). An apatite layer was formed on all the composites, with the rate of formation increasing with an increase in glass-ceramic A-W percentage. For composites with glass-ceramic A-W filler contents >or=30 vol %, the apatite layer was formed within 12 h of immersion, which is a comparable time for apatite formation on monolithic glass-ceramic A-W. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) demonstrated that the apatite formation on AWPEX samples with 50 vol % filler content occurred in a manner similar to that seen on pure glass-ceramic A-W, in that the calcium, silicon, and magnesium ion concentrations increased and, conversely, a decrease was observed in the phosphate ion concentration. These results indicate that a suitable in vitro response was achieved on a composite incorporating particulate glass-ceramic A-W with a particularly favorable response being observed on the AWPEX sample with 50 vol % filler content.

Apatite formation on CaO-free polydimethylsiloxane (PDMS)-TiO2 hybrids.

Polydimethylsiloxane (PDMS)-TiO(2) hybrids with PDMS (M=550)/tetraethylorthotitanate molar ratios at 0.27, 0.68 and 1.35, i.e. Si/Ti atomic ratios at 2, 5 and 10 (hybrids PD2, PD5 and PD10, respectively) were prepared by a sol-gel method. Hybrid PD2 formed many cracks. Hybrids PD5 and PD10 were subjected to hot-water treatment 80 degrees C for 7 d. Hybrid PD5 produced cracks, whereas hybrid PD10 was crack-free after the hot-water treatment. Hybrid PD10 took a homogeneous amorphous structure before the hot-water treatment, and precipitated anatase particles 10-20 nm in size after the hot-water treatment. Hybrid PD10 did not form apatite on its surface in a simulated body fluid before the hot-water treatment, but formed it after the hot-water treatment. The obtained hybrid showed elastic deformation as large as 200% after the hot-water treatment. This kind of hybrid could be useful as a new type of bone-repairing material.

Bioactivity and mechanical properties of polydimethylsiloxane (PDMS)-CaO-SiO2 hybrids with different calcium contents.

Polydimethylsiloxane (PDMS)-CaO-SiO(2) hybrids with starting compositions containing PDMS/(Si(OC(2)H(5))(4)+PDMS) weight ratio=0.30, H(2)O/Si(OC(2)H(5))(4) molar ratio=2, and Ca(NO(3))(2)/Si(OC(2)H(5))(4) molar ratios=0-0.2, were prepared by the sol-gel method. The apatite-forming ability of the hybrids increased with increasing calcium content in the Ca(NO(3))(2)/Si(OC(2)H(5))(4) molar ratio range 0-0.1. The hybrids with a Ca(NO(3))(2)/Si(OC(2)H(5))(4) molar ratio range 0.1-0.2 formed apatite on their surfaces in a simulated body fluid (SBF) within 12 h. The hybrid with a Ca(NO(3))(2)/Si(OC(2)H(5))(4) molar ratio of 0.10 showed an excellent apatite-forming ability in SBF with a low release of silicon into SBF. It also showed mechanical properties analogous to those of human cancellous bones. This hybrid is expected to be useful as a new type of bioactive material.

Effect of polyacrylic acid on the apatite formation of a bioactive ceramic in a simulated body fluid: fundamental examination of the possibility of obtaining bioactive glass-ionomer cements for orthopaedic use.

Glass-ionomer cements, which consist of CaO-Al2O3-SiO2-CaF2 glass powders and a polyalkenoic acid solution, such as polyacrylic acid (PAA), have been widely used in dentistry. They set rapidly without any shrinkage, the lack of temperature increase on reaction, and develop high mechanical strength. Therefore, if bioactive glass-ionomer cements can be obtained, such cements are expected to be useful as cements for fixing orthopaedic implants to the surrounding bone. In the present study, to examine the possibility of obtaining bioactive glass-ionomer cements, the effect of PAA on the apatite formation on bioactive ceramics in a simulated body fluid was investigated. It was revealed that presence of even a small quantity of PAA inhibits the apatite formation in the body environment. It is speculated that when glass-ionomer cements are implanted into the body, PAA can be released from the glass-ionomer cements and inhibits the apatite formation on their surfaces. It is reasonable to suppose that this will occur with any glass-ionomer cement that contains PAA. Therefore, it might be considered difficult to obtain bioactive glass-ionomer cements.

Process of calcification on artificial materials.

CaO, SiO2-based glasses form the bonelike apatite on their surfaces in an acellular simulated body fluid (SBF) with ion concentrations nearly equal to those of the human blood plasma. The apatite formation of the former glasses is attributed to the catalytic effect of the Si-OH groups, which are formed on their surfaces in SBF, for the apatite nucleation. The gels of SiO2, TiO2, ZrO2, Ta2O5, and Nb2O5 formed the apatite on their surfaces in SBF, but Al2O3 gel did not. This indicates that the Ti-OH, Zr-OH, Ta-OH, and Nb-OH groups besides the Si-OH groups are also effective for the apatite nucleation, but Al-OH groups are not effective. Apatite formation on self-assembled monolayer terminated with various functional groups in SBF showed that COOH and H2PO4 groups are also effective for the apatite nucleation. All these groups are negatively charged around pH 7.40. Their apatite nucleating ability is varied with their arrangements. Among the Ti-OH groups, those in anatase structure are most effective for the apatite nucleation. Transmission electron microscope attached with energy dispersive X-ray spectrometer showed that these functional groups induce the apatite nucleation not directly, but through formation of their calcium compounds and subsequent formation of amorphous calcium phosphate with low Ca/P atomic ratios.