Direct and interactive influence of explanatory variables on properties of a calcium phosphate cement for vertebral body augmentation

We used the response surface methodology to investigate the direct and interactive effects of three explanatory variables on three properties of a calcium phosphate cement (CPC) for use in vertebroplasty (VP) and balloon kyphoplasty (BKP). The variables were poly(ethylene glycol) content of the cement liquid (PEG), powder-to-liquid ratio (PLR), and the amount of Na₂HPO₄ added to an aqueous solution of 4 wt/wt% poly(acrylic acid) (as the cement liquid) (SPC). The properties were injectability (I), final setting time (F), and 5-day compressive strength (UCS). We found that (1) there was an interactive effect between the variables on I and F but not on UCS; (2) the maximum I (98 %) was obtained with PEG = 20 wt/wt% and PLR = 2 g mL^?1; (3) F = 15 min (the proposed optimum value for a CPC for use in VP and BKP) was obtained with PEG = 4 wt/wt% and PLR = 2.9 g mL^?1; and (4) the maximum UCS (39 MPa) was obtained with SPC = 0 and PLR = 3.5 g mL^?1.     

PMMA brush-containing two-solution bone cement: preparation, characterization, and influence of composition on cement properties

Two-solution bone cement consisting of poly (methyl methacrylate) (PMMA) brushes in methyl methacrylate has been developed as an alternative to the traditional two-solution (TSBC) and powder-liquid cements. It was hypothesized that the substitution of brushes, for the entire pre-polymer phase of the cement, would permit a decrease in solution viscosity at higher polymer fractions, and allow for physical entanglements with the cement matrix. Consequently, improved cement exothermal and mechanical properties could be expected with brush addition. PMMA brushes were grafted on the surface of cross-linked PMMA nanospheres following a multi-stage synthetic strategy. Brushes exhibiting optimal molecular weight for preparation of TSBC were used for characterization of cement viscosity, flexural and compressive mechanical properties, exothermal properties and residual monomer content. Interactions between grafts and free polymer formed during free radical polymerization of the cement were evaluated based on molecular weight measurements of the cement matrix and brushes. Brush-containing cements exhibited lower viscosity at significantly higher polymer fractions in comparison to TSBC. Cements with PMMA brushes had significantly lower polymerization temperatures and residual monomer content. Measurements of molecular weight revealed the existence of a dry brush regime when using the brush compositions selected in this study, which led to a reduction in the mechanical properties of some of the compositions tested. The optimal cement viscosity and maintenance of other important cement properties achieved with addition of PMMA brushes is expected to expand the use of the two-solution cements in a range of applications.     

超细玻璃纤维改性PMMA骨水泥力学性能研究

为了提高PMMA骨水泥的机械力学强度,用超细玻璃纤维对其进行改性.采用扫描电子显微镜等手段研究了超细玻璃纤维的含量以及处理方式对骨水泥拉伸强度和冲击韧性等力学性能的影响.研究表明,玻璃纤维含量(质量分数)为10%左右时材料的抗冲及抗拉性能好,同时此含量时材料的弹性模量低.用硅烷偶联剂偶联过的玻璃纤维其改性效果要优于没有偶联过的,球磨混合玻璃纤维与PMMA粉料比手工混合玻璃纤维在PMMA基体中的分散性要好,其力学性能也较手工混合的要好.     

The mechanical properties of recovered PMMA bone cement: A preliminary study

Samples of polymethylmethacrylate (PMMA) bone cement, used in the fixation of hip prostheses, have been recovered from 11 patients after in service life spans of between 15 and 24 years. Eighteen samples in total have been recovered from the acetabular and/or femoral cement. Samples were subjected to three point bending tests, their density, porosity and microhardness determined and all specimens were examined using EDX and X-ray techniques. Since the porosity of many of the samples is very high, the continuous matrix properties are inferred from the performance of individual specimens. No evidence has been found to suggest that the PMMA has deteriorated whilst in-vivo and the mechanical properties of the cement matrices appear to be comparable to freshly made PMMA.     

Effect of iodixanol particle size on the mechanical properties of a PMMA based bone cement

Iodixanol (IDX) is a water soluble opacifier widely used in radiographical examinations of blood vessels and neural tissue, and it has been suggested as a potential contrast media in acrylic bone cement. The effect of the iodixanol particle size on the polymerisation process of the bone cement, the molecular weight, and the quasi-static mechanical properties have been investigated in this article. The investigation was performed using radiolucent Palacos powder mixed with 8 wt% of iodixanol with particle sizes ranging from 3 to 20 μm MMD, compared with commercial Palacos R (15 wt% ZrO₂) as control. Tensile, compressive and flexural tests showed that smaller particles (groups with 3, 4, and 5 μm particles) resulted in significantly lower mechanical properties than the larger particles (groups with 15, 16, and 20 μm particles). There was no difference in molecular weight between the groups. The thermographical investigation showed that the IDX cements exhibit substantially lower maximum temperatures than Palacos R, with the 4 μm IDX group having the lowest maximum temperature. The isothermal and the constant rate differential scanning calorimetry (DSC) did not show any difference in polymerisation heat (ΔH) or glass transition temperature (T _g) between radiolucent cement, or cement containing either IDX, or ZrO₂. The findings show that the particle size for a bone cement containing iodixanol should be above 8 μm MMD.     

A novel sheep vertebral bone defect model for injectable bioactive vertebral augmentation materials

New injectable bone substitutes have been developed that are, unlike polymethylmethacrylate, biologically active and have an osteogenic effect leading to osteogenesis and bone remodeling for vertebroplasty or kyphoplasty. In this study, we developed a sheep vertebral bone defect model to evaluate the new bioactive materials and assessed the feasibility of the model in vivo. Bone voids were experimentally created on lumbar vertebrae L2–L5 with L1 and L6 left intact as a normal control in mature sheep. The defect vertebrae L2–L5 in each sheep were randomized to receive augmentation with calcium phosphate cement (CPC) or sham. Vertebrae (L1–L6) were collected after 2 and 24 weeks of the cement augmentation and their strength and stiffness, as well as osseointegration activity and biodegradability, were evaluated. Finally, CPC significantly improved the strength and stiffness of vertebrae but did not yet restore it to the normal level at 24 weeks. Osteogenesis occurred at a substantially high level after 24 weeks of CPC augmentation or sham. Therefore, the sheep vertebral model with one void, 6.0 mm in diameter and 15.0 mm in depth, is replicable and can be used for evaluating the new injectable bioactive materials in vertebral augmentation or reconstruction.     

Reliability of PMMA bone cement fixation: fracture and fatigue crack-growth behaviour

Fracture mechanics tests were performed to characterize the fracture toughness and fatigue crack-growth behaviour of polymethylmethacrylate (PMMA) bone cement, commonly used in joint replacement surgery. Compact tension specimens of various thicknesses were prepared and tested in both air and Ringers solution. Contrary to previous reports citing toughness as a single valued parameter, the PMMA was found to exhibit resistance-curve behaviour with a plateau toughness of 0.6 MPa m1/2 in air, and 2.0 MPa m1/2 in Ringers solution. The increased toughness in Ringers solution is thought to arise from the plasticizing effect of the environment. Under cyclic loads, the material displayed true mechanical fatigue failure in both environments; fatigue crack-growth rates, da/dN, were measured over the range 10-10 to 10-6 m/cycle and found to display a power-law dependence on the stress intensity range, K. The cement was found to be more resistant to fatigue-crack propagation in Ringers solution than in air. Wear debris was observed on the fatigue fracture surfaces, particularly those produced in air. These findings and the validity of using a linear-elastic fracture mechanics approach for viscoelastic materials are discussed in the context of providing more reliable and fracture-resistant cemented joints.     

Assessment of a three-dimensional measurement technique for the porosity evaluation of PMMA bone cement

In vitro testing of bone cement has historically resulted in the belief that porosity should be minimised to help reduce the risk of prosthesis failure through aseptic loosening. Traditional porosity measurement techniques rely on the analysis of a two dimensional representation of a three dimensional structure. However, with an increasing interest in the number, size and distribution of pores in bone cement, the reliability of a two dimensional approach is questionable. The purpose of this study was to investigate the use of micro computed tomography (micro-CT) for the three dimensional measurement of bone cement porosity by comparison with two traditional techniques. Eighteen bone cement specimens were analysed for porosity using each technique. Levels of agreement between techniques were evaluated, and technique precision was assessed in terms of repeatability and sensitivity to changes in threshold. Micro-CT data was used to illustrate the effectiveness of predicting the porosity of a whole structure from a sample region; an approach often used with traditional techniques. In summary, poor agreement was found between all techniques. However, micro-CT was found to be significantly more repeatable and less sensitive to changes in threshold. The results demonstrated that porosity cannot be reliably determined using traditional techniques and that a large proportion of a specimen is required to provide an accurate porosity measurement.     

Fatigue crack propagation under variable amplitude loading in PMMA and bone cement

Fatigue failure of PMMA bone cement is an important factor in the failure of cemented joint replacements. Although these devices experience widely varying loads within the body, there has been little or no study of the effects of variable amplitude loading (VAL) on fatigue damage development. Fatigue crack propagation tests were undertaken using CT specimens made from pure PMMA and Palacos R bone cement. In PMMA, constant amplitude loading tests were carried out at R- ratios ranging from 0.1 to 0.9, and VAL tests at R = 0.1 with 30% overloads every 100 cycles. Palacos R specimens were tested with and without overloads every 100 cycles and with a simplified load spectrum representing daily activities. The R- ratio had a pronounced effect on crack propagation in PMMA consistent with the effects of slow crack growth under constant load. Single overloads caused pronounced crack retardation, especially at low da/dN. In Palacos R, similar overloads had little effect, whilst individual overloads at low da/dN caused pronounced acceleration and spectrum loading retarded crack growth relative to Paris Law predictions. These results demonstrate that VAL can have dramatic effects on crack growth, which should be considered when testing bone cements.     

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.     

Real time monitoring of the polymerisation of PMMA bone cement using Raman spectroscopy

In this investigation Raman spectroscopy was shown to be a method that could be used to monitor the polymerisation of PMMA bone cement. Presently there is no objective method that orthopaedic surgeons can use to quantify the curing process of cement during surgery. Raman spectroscopy is a non-invasive, non-destructive technique that could offer such an option. Two commercially available bone cements (Palacos^® R and SmartSet^® HV) and different storage conditions (4 and 22°C) were used to validate the technique. Raman spectroscopy was found to be repeatable across all conditions with the completion of the polymerisation process particularly easy to establish. All tests were benchmarked against current temperature monitoring methods outlined in ISO and ASTM standards. There was found to be close agreement with the standard methods and the Raman spectroscopy used in this study.     

Study on the mechanical and biological property of PMMA bone cement modified with ultra-fine glass fibers and nano-hydroxyapatite

In this study, polymethylmethacrylate (PMMA) bone cement (BC) was modified with ultra-fine glass fibers (UFGF) and nano-hydroxapatite (nano-HAP) synthesized by hydrothermal method. The results show that when the contents of both UFGF and nano-HAP powders are about 5%, the ultimate tensile strength (UTS), ultimate impact toughness (UIT), tensile strain (TS), and elastic modulus (EM) have been promoted a lot. The interface bond was improved by silicane treatment. Pre-grinding mixture of PMMA, UFGF, and nano-HAP can largely improve the mechanical property of PMMA. The PMMA modified with UFGF and HAP has better bioactivity than that modified with pure UFGF when they share the same content. Nano-HAP powder and modified PMMA were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR).     

Microstructure and properties of α-tricalcium phosphate-based bone cement

This paper examines the physicochemical properties and microstructure of brushite calcium phosphate cements possessing strength acceptable for application in surgery (15–20 MPa) and ensuring an optimal acidity (pH 6.5–7.5) of solutions in contact with them. Holding in a physiological saline produces significant changes in the microstructure of the cement relative to that before immersion in the solution: it causes a transformation of the most soluble components into platelike hydroxyapatite crystals.     

Fracture properties of fully cured acrylic bone cement

The fracture properties of bone cement are strongly influenced by the complex interactions between the residual monomer and components of the media surrounding the bone cement. The aim of this study was to eliminate the influence of the residual monomer by fully curing the cement prior to storage in air, water, lipid or Ringer's solution at room or body temperature for up to 18 months. Subsequent mechanical testing indicated that initially there was a significant increase in the work of fracture values for all the samples stored in the fluid media. With longer-term storage periods a decrease was observed; this was attributed to the process of physical ageing. The removal of the residual monomer eliminated the monomer: lipid interaction, consequently the effect of the storage in lipid was similar to that observed for the other fluid media.     

Relationship between the morphology of PMMA particles and properties of acrylic bone cements

Bone cements are mainly based on acrylie polymers, poly (methyl methacrylate) (PMMA) being the most representative. The curing process (cold curing) is the result of the free radical polymerization of a mixture of beads of PMMA and methyl methacrylate (MMA), initiated by benzoyl peroxide (BPO) and activated by the presence of a tertiary amine, the most classical being N,N-dimethyl-4-toluidine (DMT). In this work the results on the effect of the size and size distribution of PMMA beads and the concentration of DMT and BPO on the setting parameters, the residual monomer content and the mechanical properties (tension and compression) of the cured systems are presented. The use of relatively larger diameter PMMA beads improves the characteristic parameters of the curing process (decreasing the peak temperature and increasing the setting time), without detrimental effects on the mechanical properties of the cured cement.This paper was accepted for publication after the 1995 Conference of the European Society of Biomaterials, Oporio, Portugal, 10–13 September.     

Effect of PMMA cement radical polymerisation on the inflammatory response

The effect of the radical polymerisation taking place during the hardening of the polymethyl methacrylate (PMMA) bone cements is known to cause bone necrosis through the relatively high exothermic reaction and the leaching of toxic non reacted monomers. The inflammatory response towards this class of cements has also been shown and ascribed mainly to the phagocytosis of the material particles. However, the effect of the radical polymerisation on the adsorption of plasma proteins and on the activation of monocytes/macrophages when the material is in a non-phagocytosable dimension has not been elucidated.In the present work, the polymerisation of three bone cements, CMW-1, Palavit and Simplex-P in a clinically reflective environment and its effect on the formation of a surface conditioning film as well as on the inflammatory cell activation were investigated.The data showed that on CMWand Simplex-P the polymerisation was not fully accomplished. CMW released high levels of non-reacted monomers, no significant macrophage adhesion and high oxidative burst and cytokine production. The relatively lower levels of released monomers in Simplex and Palavit seemed to promote a lower inflammatory response while cell adhesion was favoured by patches of plasma components entrapped in the hardening dough during the polymerisation.     

Influence of ibuprofen addition on the properties of a bioactive bone cement

Bioactive bone cements can promote bone growth and the formation of a strong chemical bond between the implant and bone tissue increasing the lifetime of the prosthesis. This study aims at synthesizing a new bioactive bone cement with different amounts of ibuprofen (5, 10 and 20 wt%) using a low toxicity activator, and investigating its in vitro release profile. The effect of ibuprofen (IB) on the setting parameters, residual monomer and bioactivity in synthetic plasma was also evaluated. It was verified that the different IB contents do not prevent the growth of calcium phosphate aggregates on composite surfaces, confirming that the cements are potentially bioactive. A relevant advantage of these formulations was a significant improvement in their curing parameters with increasing IB amount, associated to a reduction of the peak temperature and an extension of the setting time. The investigated cements released an average of about 20 % of the total incorporated ibuprofen during 30 days test, with IB20 liberating the highest percentage of drug 20.6 %, and IB10 and IB5, respectively 19.1 and 17.6 %. This behavior was attributed to the low solubility of this drug in aqueous media and was also related with the hydrophobic character of the polymer. Regarding the therapeutic concentration sufficient to suppress inflammation, the cement with 10 % of ibuprofen achieved the required release rate for 1 week and the cement with 20 % for 2 weeks.     

Factors affecting the mechanical and viscoelastic properties of acrylic bone cement

The aim of this paper is to report a series of experiments investigating the factors that influence the viscoelastic properties of acrylic bone cement. The effects of the brand of cement, the length of time since mixing, temperature, the hydration of the cement, and the influence of fat and or blood in the environment on the creep and stress relaxation behavior of the cement have been studied in laboratory-prepared specimens in tension, compression and four point bending. Although there are significant differences in the viscoelastic behavior of some of the different brands of polymethylmethacrylate based cements, these differences are small by comparison with the major effects that can be exerted by the length of time since mixing and some environmental factors. These effects have important practical consequences, especially with regard to the ability of bench top and theoretical studies to predict reliably the mechanical and viscoelastic behavior of acrylic cement in vivo.     

Flexural properties of crosslinked and oligomer-modified glass-fibre reinforced acrylic bone cement

The flexural properties of oligomer-modified bone cement with various quantities of crosslinking monomer with or without glass fibre reinforcement were studied. The flexural strength and modulus of acrylic bone cement-based test specimens (N=6), including crosslinked and oligomer-modified structures with or without glass fibres, were measured in dry conditions and after immersion in simulated body fluid (SBF) for seven days (analysis with ANOVA). One test specimen from the acrylic bone cement group containing 30 wt % crosslinking monomer of its total monomer content was examined with scanning electron microscope (SEM) to evaluate signs of the semi-interpenetrating polymer network (semi-IPN). The highest dry mean flexural strength (130 MPa) was achieved with the bone cement/crosslinking monomer/glass fibre combination containing 5 wt % crosslinking monomer of its monomer content. The highest flexural modulus (11.5 GPa) was achieved with the bone cement/crosslinking monomer/glass fibre combination containing 30 wt % crosslinking monomer of its monomer content. SBF storage decreased the flexural properties of the test specimens, as did the addition of the oligomer filler. Nevertheless, the addition of crosslinking monomer and chopped glass fibres improves considerably the mechanical properties of oligomer-modified (i.e. porosity-producing filler containing) acrylic bone cement. In addition, some signs of the semi-IPN structure were observed by SEM examination.