PMMA-based Bone Cement Research Articles

PMMA bone cement containing a quaternary amine comonomer with potential antibacterial properties

An iodinated quaternary amine dimethacrylate monomer was synthesized and incorporated as a comonomer in acrylic bone cements. Bone cement is used in orthopaedic surgery and imparting antibacterial properties to the cement can be beneficial in the lowering of bacterial infection post surgery. PMMA based bone cements were modified by copolymerising the monomer methylmethacrylate (MMA) with a quaternary amine dimethacrylate by using the redox initiator activator system as used for curing commercial bone cements. The cements were prepared using the commercial PMMA bone cement CMW and the liquid component was modified with the amine to render antimicrobial properties to the cement. The physical, mechanical, and antimicrobial properties of the modified cements were evaluated; in addition, the viability of the cement to function as a orthopaedic cement was also established, especially with an advantage of it being radiopaque, due to the inclusion of the iodine containing quaternary amine. The cytotoxicity of the modified cements were tested using a human cell model and the results indicated that the cells remained metabolically active and proliferated when placed in direct contact with the experimental cement specimens. The cements and their eluants did not evoke any cytotoxic response.

New Radio-opaque Acrylic Bone Cements. I. The Synthesis of Bromine Containing Methacrylates

In this work, results are presented concerning the synthesis and characterization (FTIR, 1H-NMR, 13C-NMR) of two bromine containing monomers: 2-(2-bromoisobutyryloxy) ethyl methacrylate (BIEM) and 2-(2-bromopropionyloxy) ethyl methacrylate (BPEM). The synthesis of these monomers has been made with the aim to use them as radio-opaque agents in the composition of PMMA-based bone cements. Copolymers were synthesized by free radical polymerization, using methyl methacrylate (MMA) and one of the bromine containing monomers in different concentrations. Copolymerizations were carried out directly in the thermostatic cell of an NMR spectrometer using deuterated benzene as solvent. The reactivity ratios of the copolymerization systems were determined by 1H NMR analysis.

Theoretical and Experimental Investigation of the Production of PMMA‐Based Bone Cement

AbstractPoly(methyl methacrylate) (PMMA)‐based polymers have been extensively used for manufacturing of artificial bone cements for treatment of osteoporosis. A typical bone cement recipe contains methyl methacrylate, which polymerizes in situ during cement application. An inherent problem of this reaction is the high amount of heat released during the cement preparation, which may lead to irreparable damage of living tissues. Optimization of PMMA‐based bone cement (PMMABC) recipes is thus an important step towards safe and reliable clinical usage of these materials. A theoretical and experimental investigation is performed here to unveil the influence of some preparation variables on the production of PMMABC and to allow for future optimization of the PMMABC recipe. It is shown that the degree of mixing of the components of the recipe plays a fundamental role on the development of the temperature profile. For this reason, the PMMABC obtained with the in‐situ blending of PMMA and barium sulfate during the suspension polymerization leads to much better homogeneity of the final test pieces and improved control of the temperature profile.

Development of Novel Bioactive PMMA-Based Bone Cement and its In Vitro and In Vivo Evaluation

In order to overcome the disadvantage of commercialized PMMA bone cement, we have developed novel PMMA-based bone cement(7P3S) reinforced by 30 wt.% of bioactive CaO-SiO2 gel powders to induce the bioactivity as well as to increase mechanical property for the PMMA bone cement. The novel 7P3S bone cement hardened after mixing for about 7 minutes. For in vitro evaluation, apatite forming ability of it was investigated using SBF. When the novel 7P3S bone cement was soaked into SBF, it formed apatite on its surfaces within 1 week Furthermore; there is no decrease in its compressive strength within 9 weeks soaking in SBF. It is though that hardly decrease in compressive strength of 7P3S bone cement in SBF is due to the relative small amount of gel powder or its spherical shape and monosize. In vivo evaluation of the novel 7P3S bone cement was carried out using rabbit. After implantion into rabbit tibia for several periods, the interface between novel bone cement and natural bone was evaluated by CT images. According to the results, the novel bone cement directly contact to the natural bone without fibrous tissue after implantation for 4 weeks. This results indicates that the newly developed 7P3S bone cement can bond to the living bone and also be effectively used as bioactive bone cement without decrease in mechanical property.

Mechanical and histological evaluation of a PMMA-based bone cement modified with γ-methacryloxypropyltrimethoxysilane and calcium acetate

Polymethylmethacrylate (PMMA) bone cement is widely used for prosthetic fixation in orthopaedic surgery; however, the interface between bone and cement is a weak zone. We developed a bioactive PMMA cement through modification with γ-methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. The purpose of this study was to compare the handling, mechanical and histological properties of the modified bone cement with those of the conventional cement. The modified specimens exhibited higher bonding strength between bone and implant. Histological observation and micro-focus X-ray computed tomogram (micro-CT) images showed that the modified cement exhibited osteoconduction, which the conventional PMMA bone cement lacked. The modification was found to be effective in enabling osteoconduction with PMMA bone cement, thus providing stable fixation for a long period after implantation.

DMTA analysis for long-term mechanical behaviour prediction of PMMA-based bone cements

Poly(methyl methacrylate) (PMMA) is commonly used as acrylic bone cement to fix bone implants. In vivo degradation of bone cement may lead to a decrease in mechanical properties and result in aseptic loosening. Creeping can promote failure of the implant. This study used dynamic mechanical thermal analysis (DMTA) equipment, in the 0.01 to 50 Hz frequency range, to investigate the dynamic viscoelastic relaxation characteristics of CMW™, PROFIT QUIRÚRGICO and PALACOS PMMA-based bone cements. Their initial moduli were measured as 2450, 1850 and 1710 MPa, respectively. Relaxation master curves displayed similar features. The DMTA temperature range was between 20 and 75°C. Predictions for long-term relaxation moduli were analyzed and compared against published experimental data. The comparison revealed that master curves obtain using the time-temperature-superposition principle (TTSP) present a much slower relaxation modulus compared to long-term experimental data above 1000 s. However, extrapolations based on a time-power law applied to isothermal experimental data allow better long-term predictions.

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 gamma-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 degrees 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 degrees 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.

In Vitro Aging Test for Bioactive PMMA-Based Bone Cement Using Simulated Body Fluid

Novel PMMA-based bone cement using bioactive sol-gel derived CaO-SiO2 powder in order to induce bioactivity as well as to increase its mechanical property. The novel PMMA-based bone cements formed apatite on their surfaces in Simulated Body Fluid(SBF). In the present study, a change in mechanical property of the cement was evaluated using SBF. Before soaking in SBF, its compressive strength showed 80.6±2.1MPa. After soaking in SBF for 2 weeks, 8weeks and 9 weeks, its compressive strength were changed to 83.6±1.6MPa, 87.3±2.4MPa and 85.6±1.8MPa, respectively. It is clear that from the above result, there is no decrease in its compressive strength within 9 weeks soaking in SBF. That it hardly decreases in compressive strength of 7P3S bone cement in SBF is due to the relative small amount of gel powder or its spherical shape and monosize. Therefore, the newly developed PMMA-based cement can bond to the living bone and also be effectively used as bioactive bone cement without decrease in mechanical property.

Static and fatigue mechanical behavior of bone cement with elevated barium sulfate content for treatment of vertebral compression fractures

The use of bone cement to treat vertebral compression fractures in a percutaneous manner requires placement of the cement under fluoroscopic image guidance. To enhance visualization of the flow during injection and to monitor and prevent leakage beyond the confines of the vertebral body, the orthopedic community has described increasing the amount of radiopacifier in the bone cement. In this study, static tensile and compressive testing, as well as fully reversed fatigue testing, was performed on three PMMA-based bone cements. Cements tested were Simplex ®P with 10% barium sulfate (Stryker Orthopedics, Mahwah, NJ) which served as a control; Simplex ®P with 36% barium sulfate prepared according to the clinical recommendation of Theodorou et al.; and KyphX HV-R with 30% barium sulfate (Kyphon Inc., Sunnyvale, CA). Static tensile and compressive testing was performed in accordance with ASTM F451-99a. Fatigue testing was conducted in accordance with ASTM F2118-01a under fully reversed, ±10-, ±15-, and ±20-MPa stress ranges. Survival analysis was performed using three-parameter Weibull modeling techniques. KyphX HV-R was found to have comparable static mechanical properties and significantly greater fatigue life than either of the two control materials evaluated in the present study. The static tensile and compressive strengths for all three PMMA-based bone cements were found to be an order of magnitude greater than the expected stress levels within a treated vertebral body. The static and fatigue testing data collected in this study indicate that bone cement can be designed with barium sulfate levels sufficiently high to permit fluoroscopic visualization while retaining the overall mechanical profile of a conventional bone cement under typical in vivo loading conditions.

Study on modelling of PMMA bone cement polymerisation

This contribution is concerned with the modelling of PMMA-based bone cement polymerisation process and the associated heat effect. While existing models use description in terms of the so-called polymerisation fraction to fit the experimental data, the new model is constructed in such a way as to mimic the chemical processes taking place in the cement dough. The important phenomena are identified and the mathematical formulation is proposed.

Gentamicin release from two-solution and powder-liquid poly(methyl methacrylate)-based bone cements by using novel pH method.

The release of gentamicin as a function of time was measured for Palacos and two-solution bone cements by using a novel pH technique. The pH of an aqueous solution of gentamicin is a function of the gentamicin concentration and it decreases linearly over concentrations of 0.0-0.1 wt %. Therefore, a new, direct, and inexpensive in vitro technique was developed based on continuous readings of the pH in phosphate-buffered saline (PBS) at 37 degrees C to determine the release kinetics of gentamicin from poly(methyl methacrylate) (PMMA)-based bone cement. In addition, this method was used to compare the release profiles of Palacos R-40 bone cement with a two-solution bone cement developed in our laboratory and loaded with two different concentrations of gentamicin sulfate. Finally, the pH-based method was used to track the elution of gentamicin in both mixed and static conditions to determine the effect of mixing on the diffusion of gentamicin out of the cement. It was found that Palacos R-40 released 4.95 +/- 0.22 wt % of its gentamicin after 24 h in PBS solution. This data compares favorably with previously reported values of gentamicin elution from Palacos R-40, which ranged from 3 to 8 wt % of the total amount of incorporated gentamicin, depending on the size and the surface area of the samples. The results show that Palacos samples released 4.84 +/- 0.27 mg after 24 h, a two-solution cement loaded with an equivalent concentration of gentamicin sulfate released 3.81 +/- 0.52 mg, and two-solution cement loaded with twice the concentration of Palacos released 5.53 +/- 0.26 mg of gentamicin. A higher percentage of release was recorded from Palacos than from the two-solution bone cement, and the effect of PBS mixing conditions on the release kinetics was only significant in the early stages of release and not at 24 h. It was concluded that monitoring the pH is an effective technique to measure gentamicin release from PMMA-based bone cements in PBS solution.

Thermal characterization of PMMA-based bone cement curing.

In thermal characterization tests of polymethylmethacrylate bone cement performed according to the ASTM Standard Specification for Acrylic Bone Cement, time-temperature profiles of bone cement were observed to be sensitive to the thickness of the cement patty and the mold material. Due to the heat transfer from cement to the surrounding mold, such tests might underestimate the exothermic temperature of bone cement. Developing test methods to better characterize cement thermal behavior is necessary for accurate cement curing simulations. In this paper, the effects of the mold material and geometry on experimental measurements of bone cement setting temperature and setting time were evaluated by conducting the polymerization in different test molds. Finite element (FE) numerical simulations were also performed to provide a further understanding of these effects. It was found that the mold material and geometry significantly influence the values of the parameters measured using the ASTM standard. Results showed that the setting temperature measured was about 50 degrees C lower in a polytetrafluoroethylene (PTFE) mold than in a polyurethane (PU) foam mold for the 6 mm thickness cement. The measured peak temperature using PTFE molds varied about 75 degrees C for different mold heights (6mm vs. 40 mm), but only by 28 degrees C with PU molds. The measured setting time with PTFE molds varied by about 740 s for different mold heights (6 mm vs. 40 mm), while only by about 130 s for PU molds. Using PU foam materials for the test mold decreases cement heat transfer effects due to the poor heat conductivity of PU foam and provides more consistent measured results. FE parametric studies also support these observations. Poor conductivity materials, like PU foam, make better molds for the characterization of bone cement thermal behavior.

Bioactive PMMA-based bone cement modified with alkoxysilane and calcium salts; Evaluation of apatite formation and bone-bonding ability.

Bioactive PMMA-based bone cement modified with alkoxysilane and calcium salts; Evaluation of apatite formation and bone-bonding ability.

Development of Novel PMMA-Based Bone Cement Reinforced by Bioactive CaO-SiO<sub>2</sub> Gel Powder

Development of Novel PMMA-Based Bone Cement Reinforced by Bioactive CaO-SiO<sub>2</sub> Gel Powder

Dynamic mechanical behavior of PMMA based bone cements in wet environment.

The mechanical properties of three wet commercial bone cements, namely Braxel (from Bioland), Simplex-P (from Howmedica) and CMW1-G (from DePuy) are investigated by means of stress relaxation and dynamic mechanical analysis (DMA). The geometry of loading that was used is the three point bending method (ASTM D790); all the tests were performed in a water chamber by means of temperature sweeps between 17 and 57 degrees C and spanning four frequency decades. The results show that viscoelastic properties are strongly dependent on specimen conditioning (i.e. water uptake and heat treatment). The results also show that all the cements that were analyzed show mechanical properties which are intermediate between the ones of the cancellous bone and of the metals of which prostheses are normally made. As a consequence, the cement is able to reduce the stress concentrations due to the interfacing of materials which have very different stiffnesses. Moreover, the results of the DMA, particularly the ones concerning the damping factor (tan delta), indicate that at body temperature the bone cements tested show an increased capacity of dissipation, the higher is the loading frequency, thus displaying shock absorbing properties.

Effect of triphenyl bismuth on glass transition temperature and residual monomer content of acrylic bone cements

Self-curing acrylic bone cements are widely used in the fixation of prosthetic implants in orthopaedic surgery. Commercial bone cements are rendered radiopaque by the addition of heavy metal salts of barium and zirconia. The addition of barium sulphate adversely affects the mechanical strength and fracture toughness of bone cement and despite the fact that it has low solubility in water; its slow release and subsequent toxicity have caused concern. In an earlier study triphenyl bismuth (TPB) was found to be a viable alternative as a radiopaque agent in acrylic bone cements, which provided enhanced homogeneity. In this study we report the effect of the inclusion of TPB on the thermal properties of PMMA-based bone cements using both conventional DSC and Modulated Temperature DSC. Furthermore, analysis of the residual monomer contents is reported analysed by NMR spectroscopy in order to ascertain the influence of TPB on the polymerisation reaction. The glass transition temperature (T g) determined by DSC showed that the values decreased with the addition of increasing amounts of TPB through both blending and dissolution methods; however, the method of incorporating TPB did not influence T g. The magnitude of reduction was dependent of the amount of TPB and was greatest in the case of highest concentration of TPB used. A TPB melting peak was observed in the 25 wt% TPBBC, suggesting a limit to the solubility of TPB. The residual monomer analysis showed that at 10 and 15% by weight of TPB in the cement caused no significant changes in the residual monomer content but 25 wt% of TPB exhibited a significantly higher residual monomer content.

Bioactive PMMA-Based Bone Cement Modified with Methacryloxypropyltrimethoxysilane and Calcium Salts-Effects of Calcium Salts on Apatite-Forming Ability-

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 essential prerequisite for an artificial material to bond to bone is the formation of an apatite layer on its surface when implanted in a bony defect. This apatite layer can be, for example, formed in a simulated body fluid (Kokubo solution) with ion concentrations similar to those of human extracellular fluid. The present authors recently showed the potential of bioactive PMMA-based bone cement through modification with y-methacryloxypropyltrimethoxysilane (MPS) and calcium chlorides. In this study, the effects of the kinds of calcium salts on apatite-forming ability were examined by exposure to Kokubo solution. PMMA powder (molecular weight of 100000 and 14 μm in average particle size) was mixed with 20 mass% of calcium salts consisting of calcium chloride (CaCl 2 ), calcium acetate (Ca(CH 3 COO) 2 ), calcium hydroxide (Ca (OH) 2 ), calcium lactate (Ca(CH 3 CHOHCOO) 2 ), calcium benzonate (Ca(C 6 H 5 COO) 2 ) and calcium methacrylate (Ca(CH 2 = C (CH 3 )COO) 2 ), while 20 mass% of MPS was added in the MMA liquid. The appropriate setting time was obtained by the usage of calcium acetate or calcium lactate, although the modification with MPS and calcium salts leads to an elongation of the setting time of the cement. Apatite formation could be detected after soaking in Kokubo solution for 1 d when the cements were modified with calcium chloride, calcium acetate, or calcium methacrylate. Apatite formation could be observed on the modified cement with calcium hydroxide after 7 d of soaking in Kokubo solution. The higher solubility of calcium salts allows for a higher rate of apatite formation in Kokubo solution. Furthermore, changes in pH after exposure of the cement are related to the apatite-forming ability, because the addition of calcium hydroxide also gives the cement the ability of apatite formation, even if the cement releases a small amount of calcium ions into the surrounding fluid. Smaller dissolution of calcium salts results in less decrease in compressive strength after exposure to a body environment. The release of calcium ions, followed by changes in pH, must be controlled to achieve a successful design of bioactive PMMA bone cement by modification with MPS and calcium salts.

Development of bioactive organic–inorganic hybrid for bone substitutes

Bioactive glasses and glass–ceramics have been attractive because they spontaneously bond to living bone when implanted in bony defect. However, they are much more brittle and much less flexible than natural bone. Hybridization of essential constituents of bioactive glasses and glass–ceramics with flexible polymer can solve this problem. The present topic is devoted to the design of organic–inorganic hybrids that can bond to living bone. Previous studies reported that the condition for bioactive glasses and glass–ceramics to achieve direct bond to living bone is formation of a bone-like apatite layer on their surfaces after exposure to the body fluid. The same type of apatite formation can be observed even in a simulated body fluid (Kokubo solution) proposed by Kokubo and his colleagues. Glasses in the binary system CaO–SiO2 showed the apatite formation in Kokubo solution. The formation of the surface apatite is induced both by dissolution of calcium ions from the bioactive glass, and by silanol (Si–OH) group in the hydrated silica gel formed on the surface. These findings bring an idea that incorporation of calcium ion (Ca2+) and Si–OH group into organic substances leads to a bioactive hybrid. It was confirmed that organic–inorganic hybrids containing calcium salt, which were synthesized from vinyltrimethoxysilane (VS) or 3-methacryloxypropyltrimethoxysilane (MPS), showed the apatite formation in Kokubo solution. Such type of organic–inorganic hybrids can be blended with organic polymer. An organic–inorganic hybrid was synthesized from MPS and 2-hydroxyethylmethacrylate (HEMA) at a composition of MPS/HEMA=0.1:0.9. The MPS–HEMA hybrid also formed the apatite layer when the hybrid was incorporated with calcium chloride. Incorporation of MPS and calcium salt also provides conventional PMMA-based bone cement with the ability of apatite formation. These findings indicate that novel bioactive materials can be developed from organic–inorganic hybrids obtained by incorporation of calcium ion and specific kinds of functional groups such as Si–OH.

Flexural strength distribution of a PMMA-based bone cement

Flexural strength distribution of a PMMA-based bone cement

522 化学修飾により骨親和性を付与した PMMA 系骨セメントの力学的特性

PMMA-based bone cement is commercially used for anchoring implants, such as artificial hip joints, with bone. However, it has a major problem on prosthesis loosening due to coverage by fibrous tissues after long-term implantation. A novel design of bone cement exhibiting bone-bonding ability i. e. bioactivity is desired. In order for artificial materials to bond directly to bone, formation of an apatite layer on the artificial surface is prerequisite. This apatite formation is triggered both by release of calcium ions (Ca^<2+>) from the materials, and by catalytic effect on induction of apatite nucleation by silanol (Si-OH) groups on their surfaces. The present authors have recently developed bioactive PMMA-based bone cement through modification with γ-methacryloxypropyltrimethoxysilane (MPS) and various kinds of calcium salts. In this study, effects of chemical modification on its mechanical properties were examined in a simulated body fluid (SBF). Four point bending strength of modified cements after soaking in SBF increased in the order : Ca(OH)_2 < Ca(CH_3COO)_2 < Commercial bone cement < No modification (Reference).