Synthesis of bioactive PMMA bone cement via modification with methacryloxypropyltri- methoxysilane and calcium acetate

Bone cement consisting of polymethylmethacrylate (PMMA) powder and methylmethacrylate (MMA) liquid is clinically used for fixation of implants such as artificial hip joints. However, it does not show bone-bonding ability, i.e., bioactivity. The lack of bioactivity would be one of factors which cause loosening between the cement and the implant. The present authors recently showed the potential of bioactive PMMA-based bone cement through modification with γ -methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. In this study, the effects of the kinds of PMMA powder on setting time, apatite formation and compressive strength were investigated in a simulated body fluid (Kokubo solution). The cement modified with calcium acetate calcined at 220 ^∘C could set within 15 min when the PMMA powder had an average molecular weight of 100,000 or less. The addition of calcium acetate calcined at 120 ^∘C in the PMMA powder required a much longer period for setting. The modified cements formed an apatite layer after soaking in the Kokubo solution within 1 day for cement starting from PMMA powder with a molecular weight of 100,000 or less. Compressive strengths of the modified cements were more than 70 MPa for cements starting from 100,000 and 56,000 in molecular weight. After soaking in Kokubo solution for 7 days, the modified cement consisting of PMMA powder of 100,000 in molecular weight showed a smaller decrease in compressive strength than that consisting of 56,000 in molecular weight. These results indicate that bioactive PMMA cement can be produced with appropriate setting time and mechanical strength when PMMA powders with a suitable molecular weight are used. Such a type of design of bioactive PMMA bone cement leads to a novel development of bioactive material for bone substitutes.     

Synthesis of bioactive organic-inorganic nanohybrid for bone repair through sol-gel processing

So-called bioactive ceramics have been attractive because they form bone-like apatite on their surfaces to bond directly to living bone when implanted in bony defects. However, they are much more brittle and much less flexible than natural bone. Organic-inorganic hybrids consisting of flexible organic polymers and the essential constituents of the bioactive ceramics (i.e., Si-OH groups and Ca2+ ions) are useful as novel bone substitutes, because of their bioactivity and mechanical properties analogous to those of natural bone. In the present study, organic-inorganic nanohybrids were synthesized from hydroxyethylmethacrylate (HEMA) and methacryloxypropyltrimethoxysilane (MPS), as well as various calcium salts. Bioactivity of the synthesized hybrids was assessed in vitro by examining their acceptance of apatite deposition in simulated body fluid (Kokubo solution). The prepared hybrids formed apatite in Kokubo solution when they were modified with calcium chloride (CaCl2) at 5 or 10 mol% of the total of MPS and HEMA. Deposition of a kind of calcium phosphate was observed for the hybrids modified with calcium acetate (Ca(CH3COO)2), although it could not be identified with apatite. The addition of glycerol up to 10 mol% of the total of MPS and HEMA or water up to 20 mol% as plasticizers did not appreciably decrease the acceptance of apatite formation of the hybrids. These findings allow wide selectivity in the design of bioactive nanohybrids developed by organic modification of the Si-OH group and calcium ion through sol-gel processing. Such nanohybrids have potential as novel bone substitutes with both high bioactivity and high flexibility.     

Relationship between apatite-forming ability and mechanical properties of bioactive PMMA-based bone cement modified with calcium salts and alkoxysilane

Polymethylmethacrylate (PMMA)-based bone cement is used for the fixation of artificial joints in orthopaedics. However, the fixation is liable to loosen in the body, because the cement does not bond to living bone. So-called bioactive ceramics bond directly to living bone through the apatite layer formed on their surfaces in the body. We previously revealed that modification using γ-methacryloxypropyltrimethoxysilane (MPS) and water-soluble calcium salts such as calcium acetate and calcium hydroxide was effective for providing the PMMA-based bone cement with apatite-forming ability in a simulated body fluid (SBF, Kokubo solution) that closely reproduces the body environment. However, the effect of the chemical reaction forming the apatite on the mechanical properties of the cements has not been clarified. The present work aimed to investigate this issue from the viewpoint of the interface structure between the apatite and the cement. The surface of the cement modified with calcium acetate and MPS was fully covered with newly formed apatite after soaking in Kokubo solution within 7 days, while half of the surface area of the cement modified with calcium hydroxide and MPS was covered with the apatite. The bending strength of the modified cements decreased after soaking in Kokubo solution. Porous structure was observed in the region about 50–100 μm in depth from the top surface because of release of the Ca²⁺ ions by both modified cements after soaking in Kokubo solution. The decrease in bending strength of the modified cements could be attributed to the formation of the pores. In addition, the pores on the top surfaces of the cements were filled with the newly formed apatite. The apatite formation would be effective not only for bioactivity but also for decreasing the reduction of mechanical strength.     

Acceleration of calcium phosphate formation on bioactive PMMA-based bone cement by controlling spatial design

Polymethylmethacrylate (PMMA)-based bone cement is widely used for the fixation of artificial joints. However, it is not considered a bioactive material because it lacks the ability to induce a direct bond with bone. In order to improve the long-term stability of cemented fixations, the development of bioactive bone cements is desirable. An essential requirement of a bioactive material includes the induction of bone-like apatite on its surface within the in vivo environment. Previously, we prepared bioactive PMMA-based bone cements by a modification with water-soluble calcium salts and alkoxysilane. Because spatial design may enhance apatite formation on bioactive material surfaces in vivo, we aimed to evaluate the effect of spatial design on apatite formation on modified PMMA-based bone cements in simulated body fluid (SBF). We found that an appropriate spatial design shortened the induction period for the apatite deposition on the modified bone cements. It is expected that osteoconduction would be enhanced in spontaneously created gap between the cement and the host bone leading to tight integration.     

In vitro study of nano-sized zinc doped bioactive glass

Surface reactivity in physiological fluid has been linked to bioactivity of a material. Past research has shown that bioactive glass containing zinc has the potential in bone regeneration field due to its enhanced bioactivity. However, results from literature are always contradictory. Therefore, in this study, surface reactivity of bioactive glass containing zinc was evaluated through the study of morphology and composition of apatite layer formed after immersion in simulated body fluid (SBF). Nano-sized bioactive glass with 5 and 10 mol% zinc were synthesized through quick alkali sol–gel method. The synthesized Zn–bioglass was characterized using field emission scanning electron microscope (FESEM), energy dispersive X-ray spectrometer (EDX), X-ray diffractometer (XRD) and Fourier transform infrared spectrometer (FTIR). Samples after SBF immersion were characterized using scanning electron microscope (SEM) and EDX. Morphological study through SEM showed the formation of spherical apatite particles with Ca/P ratio closer to 1.67 on the surface of 5 mol% Zn–bioglass. Whereas, the 10 mol% Zn–bioglass samples induced the formation of flake-like structure of calcite in addition to the spherical apatite particles with much higher Ca/P ratio. Our results suggest that the higher Zn content increases the bioactivity through the formation of bone-bonding calcite as well as the spherical apatite particles.     

Ultrasonic implantation of calcium metasilicate glass particles into PMMA

Polymer materials for clinical applications should be bioactive and have a bone-bonding ability. In order to provide poly(methyl methacrylate) (PMMA) with bioactivity, granules (<45 m) of a bioactive glass 50CaO·50SiO2 (mol %) were implanted into PMMA: they were suspended together with a piece of PMMA in a 40 tetrahydrofuran-60 ethanol (vol %) solution and ultrasonically agitated. The granules of <10 m in size were impregnated at 40–20 m depth below the substrate surface. Two types were detected on the PMMA surface: (a) a glass-granule layer on PMMA, and (b) an inner granule layer, a PMMA layer, and an outer granule layer on the PMMA. The bioactivity of the implanted PMMA substrates was examined in vitro with a simulated body fluid (Kokubo solution). Apatite was precipitated on all glass granules and the whole substrate surfaces within 1 d. After 4 h soaking in the Kokubo solution, aggregates of apatite particles appeared on the substrate surface, independently of those on the glass granules, and they grew and proliferated on the whole subtrate surface in 7 d. Silica gel islands on PMMA due to the silicate anions from the glass were considered to induce nucleation of the apatite particles.     

Apatite formation abilities and mechanical properties of hydroxyethylmethacrylate-based organic–inorganic hybrids incorporated with sulfonic groups and calcium ions

Apatite formation in the living body is an essential requirement for artificial materials to exhibit bone-bonding bioactivity. It has been recently revealed that sulfonic groups trigger apatite nucleation in a body environment. Organic–inorganic hybrids consisting of organic polymers and the sulfonic groups are therefore expected to be useful for preparation of novel bone-repairing materials exhibiting flexibility as well as bioactivity. In the present study, organic–inorganic hybrids were prepared from hydroxyethylmethacrylate (HEMA) in the presence of vinylsulfonic acid sodium salt (VSAS) and calcium chloride (CaCl₂). The bioactivities of the hybrids were assessed in vitro by examining the apatite formation in simulated body fluid (SBF, Kokubo solution). The hybrids deposited on the apatite after soaking in SBF within 7 days. Tensile strength measurements showed a tendency to increase with increases in VSAS and CaCl₂ content. It was assumed that this phenomenon was attributed to the formation of cross-linking in the hybrids.     

Bioactivity of metallic biomaterials with anatase layers deposited in acidic titanium tetrafluoride solution

A simple and versatile treatment was developed to provide various metallic biomaterials such as Ti, NiTi, Ta and SUS 316L stainless steel with in vitro bioactivity or ability to deposit carbonate-incorporated apatite in a simulated body fluid (Kokubo solution). A well-crystallized anatase layer deposited on the metallic biomaterials surfaces after soaking them at 60 degrees C for 24 h in an aqueous solution of titanium tetrafluoride (40 mM) whose pH was adjusted to 1.9 with HCl. The as-coated anatase layers did not deposit apatite. When heated at 300 degrees C they were so bioactive as to deposit apatite within 5 day(s) in the Kokubo solution. The trace amount of fluorine weakly bound in the as-coated anatase layers was suggested to be one of the factors that suppressed the bioactivity.     

Design of bioactive bone substitutes based on biomineralization process

A material able to form bone-like apatite on its surface in the living body bonds to living bone through the apatite layer. Functional groups such as Si-OH, Ti-OH, Zr-OH, Nb-OH and Ta-OH induce apatite formation in the living body. On the basis of these findings, various kinds of bioactive materials with different mechanical properties can be designed. For example, bioactive titanium metal, its alloys and tantalum metal can be obtained by forming a thin sodium titanate or tantalate layer on their surfaces by NaOH solution and heat treatments.Bioactive organic polymers can be obtained by forming a thin CaO–SiO₂ or TiO₂ layer on their surfaces by a sol–gel method. These bioactive materials are believed to be useful as unique bone substitutes.     

Bonding ability evaluation of bone cement on the cortical surface of rabbit’s tibia

A composite bone cement designated G2B1 that contains β tricalcium phosphate particles was developed as a bone substitute for percutaneous transpedicular vertebroplasty. In this study, both G2B1 and commercial PMMA bone cement (CMW1) were implanted into proximal tibiae of rabbits, and their bone-bonding strengths were evaluated at 4, 8, 12 and 16 weeks after implantation. Some of the specimens were evaluated histologically using Giemsa surface staining, contact microradiography (CMR) and scanning electron microscopy (SEM). Histological findings showed that G2B1 contacted bone directly without intervening soft tissue in the specimens at each time point, while there was always a soft tissue layer between CMW1 and bone. The bone-bonding strength of G2B1 was significantly higher than that of CMW1 at each time point, and significantly increased from 4 weeks to 8 and 12 weeks, while it decreased significantly from 12 weeks to 16 weeks. Bone remodeling of the cortex under the cement was observed especially for G2B1 and presumably influenced the bone bonding strength of the cement. The results indicate that G2B1 has bioactivity, and bone bonding strength of bioactive bone cements can be estimated fairly with this experimental model in the short term.     

Bioactivity of sol–gel derived organically modified silicates: Part I: In vitro examination

Bioactivity was investigated for several organically modified silicates (Ormosils) prepared through sol–gel processes. Ca(II)-free samples were biocompatible only, but Ca(II)containing samples were bioactive and deposited apatite during immersion in a simulated body fluid. The ease of silanol (Si–OH) group formation on the ormosils was considered a predominant factor controlling the bioactivity, while the effect of dissolved Ca(II) ions to increase the degree of supersaturation in the simulated body fluid is secondary.     

Preliminary investigation of bioactivity of nano biocomposite

Bioactive biomaterials can form a bone-like apatite layer on their surfaces in the body, which is critical to establishing bone bonding between bioactive materials and living tissue. At present study, the bone-like apatite formation in vitro and vivo on the surface of the nano apatite/polyamide composite was studied, and the bioactive composites implanted into the femora of rabbits were also investigated. The results revealed that the bone-like apatite containing carbonate can form on the surface of the biocomposite both in SBF and dorsal muscle of rabbits, and the composite would form directly combination with the natural bone without fibrous capsule tissue between implant and host bone tissue. All of these indicated that the nano biocomposites have excellent bioactivity and can be used for bone replacement.     

New chemical treatment for bioactive titanium alloy with high corrosion resistance

It was recently claimed that titanium metal and its alloys can bond to the living bone, without being coated by apatite (VPS coatings), but by being chemically and heat-treated. The bioactivity of treated titanium is of interest because of the opportunity to obtain orthopaedic or dental implants presenting, at the same time, high toughness, strength and fatigue resistance as well as bone-bonding ability. The bioactive behaviour of the treated implants is due to the presence of a modified surface, which, during soaking in body fluid, promotes the precipitation of apatite. The apatite formed is strongly bonded to the substrate and promotes living bone bonding. In this work were characterised samples of Ti-6Al-7Nb alloy with surfaces presenting a different chemical and mechanical state. The aim of the research was twofold. The first objective was to characterise chemically and heat-treated samples with different surface topography, in order to define the best conditions for osteogenic integration. The second aim was to assess the corrosion behaviour of the bioactive implants, because they expose a microporous and quite thin modified surface layer. No-treated and passivated samples, with a surface state closed to that nowadays used on implants, were used as reference. The surface structure, morphology, electrochemical behaviour and bioactivity of the different samples were assessed by means of XRD, SEM-EDS, anodic polarizations, open circuit measurements and in-vitro tests. Results evidence that it is possible to modify the surface of the Ti-6Al-7Nb alloy in order to obtain the formation of a bioactive layer and that the substrate roughness influences the characteristics of the surface layer formed. It was also evidenced that the as treated surfaces present inadequate corrosion behaviour, so a new two-step chemical treatment has been developed in order to obtain a bioactive material with good corrosion resistance.     

Viscoelastic Properties and Bioactivity of Sol-Gel Derived Gelatin-Silicate Composites: Effects of the Incorporated Ca2+ Ions

Several gelatin-silicate composites, with or without incorporation of Ca2+ ions, were synthesized through set-gel processing starting from gelatin and 3- (glycidoxypropyl) trimethoxysilane. The structure around the Si atoms was similar for all the samples. The measurement of viscoelastic properties indicated that the glass transition temperature and activation energy decreased with the incorporation of Ca2+ ions. The Ca2+ ion-containing composites were bioactive as they spontaneously deposited apatite when soaked in a simulated body fluid of the Kokubo recipe.     

Microstructure and chemistry affects apatite nucleation on calcium phosphate bone graft substitutes

The bioactivity of calcium phosphate bone grafts of varying chemistry and strut-porosity was compared by determining the rate of formation of hydroxycarbonate apatite crystals on the material surface after being soaked in simulated body fluid for up to 30 days. Three groups of silicate-substituted hydroxyapatite material were tested, with each group comprising a different quantity of strut-porosity (23, 32, and 46 % volume). A commercially available porous β-tricalcium phosphate bone graft substitute was tested for comparison. Results indicate that strut-porosity of a material affects the potential for formation of a precursor to bone-like apatite and further confirms previous findings that β-tricalcium phosphate is less bioactive than hydroxyapatite.     

Enhancement of bonding strength by graded structure at interface between apatite layer and bioactive tantalum metal

Tantalum metal is a candidate for use as an implant material in high load-bearing bony defects, due to its attractive features such as high fracture toughness and high workability. This metal, however, does not have bone-bonding ability, i.e. bioactivity, and therefore the development of bioactive tantalum metal is highly desirable. It is known that the essential prerequisite for an artificial material to show bioactivity is to form a bonelike apatite layer on its surface in the body environment. The same type of apatite layer is formed in a simulated body fluid (SBF) with inorganic ion concentrations nearly equal to those of human blood plasma. The present authors previously showed that the apatite formation on tantalum metal in SBF was remarkably accelerated by treatment with 0.5 M-NaOH aqueous solution and subsequent firing at 300 °C, while untreated tantalum metal spontaneously formed the same apatite after a long soaking period. In the present study, the bonding strength of the apatite layer to the substrate was quantitatively evaluated in comparison with that to the untreated tantalum metal. Adhesive strength was measured as an estimation of bonding strength, and the surface microstructure of both the substrates was characterized in order to discuss the difference in the bonding strength in terms of surface structure. The apatite layer formed on the NaOH- and heat-treated tantalum metal shows higher adhesive strength than that formed on the untreated metal. The amorphous sodium tantalate layer formed on the tantalum metal by NaOH and heat treatments, has a smooth graded structure where its concentration gradually changes from the surface into the interior metal. Smooth graded structure with complex of apatite is constructed after soaking in SBF. The higher bonding strength of the apatite layer formed on the treated metal is attributed to its smooth graded structure.     

Apatite wollastonite–poly methyl methacrylate bio-composites

Bio-composites consisting of sol–gel processed apatite wollastonite (AW) glass ceramics and poly methyl methacrylate (PMMA) were prepared by hot compaction method. Density of the composites decreased with increase in PMMA content, while, biaxial flexural strength (BFS) was 21 MPa for 20 wt.% PMMA and beyond which it decreased. A correlation between phase compositions of AW glass ceramics with BFS was attempted from the XRD results. In vitro bioactivity of the composites in a simulated body fluid (SBF) showed the formation of spherical globules on the surface within 7 days of soaking as observed by environmental SEM. Thin film XRD and EDX measurement confirmed these globules to be bone like apatite with Ca/P ratio 1.53 and FTIR measurement showed the corresponding peaks for phosphates. Results indicated the bone bonding ability of the composites by forming a surface apatite (calcium phosphate) layer in SBF and the growth increased with increase in soaking durations. ICP measurement of the remaining SBF after 7, 14 and 21 days soaking of samples was found to be in good agreement with the EDX analysis results.     

Bioactivity of gelatin coated magnetic iron oxide nanoparticles: in vitro evaluation

Current research explores formation of bone like apatite on gelatin coated magnetic iron oxide nanoparticles (GIOPs) to evaluate the bioactivity of the material. The GIOPs were soaked in simulated body fluid (SBF) and the apatite formation on the surface was investigated in regular interval of time. Fourier transform-infrared (FT-IR) and x-ray diffraction spectroscopic (XRD) analyses were done to investigate the chemical changes and field emission-scanning electron microscopic (FE-SEM) analysis was done to investigate the morphological changes occurring on the surface of the GIOPs after soaking in different time intervals. The kinetic studies of the apatite growth in SBF suggest that initially calcium and phosphorous ions were deposited to the surface of the GIOPs from the SBF leading to formation of amorphous Ca/P particles. Later, after 9 days of the incubation the amorphous particles were fused to form needle and blade like crystalline structures of bone like apatite.     

Apatite-forming ability of polyglutamic acid hydrogels in a body-simulating environment

Artificial joints can replace damaged joints provided the surrounding bone is sufficiently dense. However, elderly patients generally have reduced osteoporosis-associated bone density. Therefore, restitution of bone density is essential to ensure implantation. Injectable and resorbable bioactive fillers with bone-bonding ability (osteoconductivity) are promising, as osteoporosis can be reversed with minimal invasion. Osteoconduction occurs through the surface formation of biologically active hydroxyapatite via reactions with body fluids. Heterogeneous nucleation of the hydroxyapatite is catalysed by specific surface functional groups. In addition, release of Ca²⁺ ions into the surrounding fluids enhances apatite nucleation by increasing its degree of supersaturation. We tested injectable bioactive filler made from cross-linked polyglutamic acid (PGA). This has many carboxyl groups that facilitate apatite nucleation. An insoluble hydrogel can be formed by cross-linkage. We exposed PGA gels to a simulated body fluid for 7 days. Trace amounts of calcium phosphate were formed, but were not identified as bone-like apatite by X-ray diffraction. However, formation of a bone-like apatite layer was detected using pre-treatment with CaCl₂ solutions (>0.01 mol dm⁻³) dose dependently. Thus, this chemically cross-linked PGA gel could induce the heterogeneous nucleation of hydroxyapatite in a body environment, and this was enhanced by pre-treatment with CaCl₂.     

Chemical reaction of bioactive glass and glass-ceramics with a simulated body fluid

Glass-ceramic A-W containing crystalline apatite and wollastonite in an MgO-CaO-SiO₂ glassy matrix bonds to living bone through an apatite layer which is formed on its surface in the body. The parent glass G of glass-ceramic A-W and glass-ceramic A, which has the same composition as glass-ceramic A-W but contains only the apatite, also bond to living bone through the surface apatite layer, whereas glass-ceramic A-W(Al), which contains the apatite and wollastonite in an MgO-CaO-SiO₂-Al₂O₃ glassy matrix, neither forms the surface apatite layer nor bonds to living bone. In the present study, in order to reveal the mechanism of formation of the surface apatite layer, changes in ion concentrations of a simulated body fluid with immersion of these four kinds of glass and glass-ceramics were investigated. Bioactive glass G and glass-ceramics A and A-W all showed appreciable increases in Ca and Si concentrations, accompanied by an appreciable decrease in P concentration, whereas non-bioactive glass-ceramic A-W(Al) hardly showed any element concentration change. It was speculated from these results that dissolution of the Ca(II) and Si(IV) ions from bioactive glass and glass-ceramics plays an important role in forming the apatite layer on their surfaces in the body.