Biocompatibility of a new radiopaque iodine-containing acrylic bone cement

Radiopacity in the vast majority of the commercially available acrylic bone cements that are used clinically is provided by particles of either BaSO(4) or ZrO(2). Literature reports have shown these agents to have a detrimental effect on some mechanical properties of the cements as well as on its biological response. We, therefore, have developed a new type of bone cement, for which radiopacity results from the presence of an iodine-containing methacrylic copolymer. The focus of the present work was the comparison of the biocompatibility of this new cement and a commercially available cement that contains barium sulfate. In vitro experiments show that both cements are cytocompatible materials, for which no toxic leachables are found. Implantation of the cements in a rabbit for three months resulted in the occasional presence of a thin fibrous tissue at the cement-bone interface, which is common for acrylic bone cements. Consideration of all the results led to the conclusion that the new cement is as biocompatible as the BaSO(4)-containing one.     

Mechanical properties of oligomer-modified acrylic bone cement

The aim of this study was to determine the mechanical properties of acrylic bone cement modified with an experimental oligomer filler, based on an amino acid of trans-4-hydroxy-L-proline synthesized in the laboratory. The test specimens were tested either dry, or after being stored in distilled water or in simulated body fluid (SBF) for 1 week and then tested in distilled water. The three-point bending test was used to measure the flexural strength and flexural modulus of the cement, and the compression tests were used to measure the compression strength and modulus. One test specimen from each group was examined under a scanning electron microscope (SEM) to determine the nature of the oligomer filler in the polymethylmethacrylate-polymethylacrylate copolymer-based (PMMA-PMA/PMMA) polymer blend. In dry conditions, the flexural strength of the test specimens tested in air was 66 MPa, and the compression strength was 93 GPa (p<0.001) for the plain bone cement. For the test specimens including 20 wt% of oligomer filler, the flexural strength was 37 MPa, and the compression strength was 102 MPa(p<0.001) in dry conditions. The storage in wet conditions (in distilled water and the SBF) decreased the flexural strength of the test specimens with 20 wt% of oligomer filler (p<0.001) by 60% and the flexural modulus by 44% compared to the plain bone cement specimens stored in the same conditions. The reduction in compression strength in wet conditions was 32%, and that of the compression modulus was 30% (p<0.001). No significant differences were found between test specimens stored in distilled water or SBF (ANOVA, p<0.001). In the SEM examinations, random voids were observed in the oligomer-PMMA-PMA/PMMA polymer blend after water or SBF storage. The results suggest that both water and SBF storage decrease the mechanical properties of the PMMA-PMA/PMMA bone cement modified with oligomer, while at the same time, there was porous formation in the bone cement structure.     

Evaluation of a highly-radiopaque iodine-containing acrylic bone cement for use in augmentation of vertebral compression fractures

Vertebroplasty and balloon kyphoplasty are widely used for the augmentation of osteoporosis-induced vertebral compression fractures. Almost invariably, an injectable poly(methyl methacrylate) (PMMA) bone cement that contains a large amount of BaSO(4) particles is used in these procedures. The deleterious effects of this radiopacifier on various properties of PMMA cement have been detailed in the literature. The objective of the present study was therefore to avoid such high levels of inorganic contrast agent and thus to develop an all-polymeric bone cement, for which radiopacity was provided by 60 wt % of an iodine-containing methacrylic copolymer, incorporated into the powder (IO cement), ultimately leading to 6.6 wt % of iodine in the cement. A large array of properties of this cement were determined, ranging from setting time and injectability to fatigue life under fully-reversed tension-compression loading and cytotoxicity, and a comprehensive comparison with a cement containing 30 wt % BaSO(4) in the powder component (BA cement) has been made (11 wt % of Ba in the cement). Statistical analyses of the results showed that, for the majority of the properties, the difference between the means for the two cements was not significant. It is therefore suggested that the IO cement is a suitable alternative to the BA cement for use in the aforementioned procedures.     

Stability of radiopaque iodine-containing biomaterials.

Stability tests have been performed on two typical iodine-containing radiopaque poly(methacrylate) copolymers. Material A is a terpolymer of methylmethacrylate (MMA), 2-hydroxyethyl methacrylate (HEMA) and 2-[4-iodobenzoyl]-oxo-ethylmethacrylate (4-IEMA); material B is a copolymer of MMA and 4-IEMA. Cylindrical specimens of material A were implanted subcutaneously and intraperitoneally in Wistar rats. The implants were retrieved after 2 years. Histology showed that the material was well-tolerated. Detailed analysis of the surface of the implants by electron spectroscopy for chemical analysis (ESCA) revealed that the material remained stable. No differences could be detected between the ESCA spectra of the explants, and those of the control specimens, which were from the same synthetic batch and which were stored in dry form during the entire experimental period. Material B was also stable upon irradiation with X-rays in vitro, even at high doses, compared to the clinical situation. Exposure of material B to gamma-radiation, however, was found to lead to structural degradation. This was evident from clear yellowing, and also from the ESCA spectra. The spectra revealed that material B deteriorates during gamma-irradiation through rupture of C-C and or C-O chemical bonds, not via C-I bond disruption. It can be concluded that iodine is tightly bound to these radiopaque biomaterials. This is important with regard to potential applications of these materials as implant biomaterials.     

Water uptake and release from iodine-containing bone cement

Water uptake and release characteristics of PMMA cement containing the water-soluble contrast media iohexol or iodixanol have been investigated. The water uptake study revealed that iohexol had the highest uptake of water (3.7%) and that iodixanol had an uptake close to that of Palacos R (2.3% and 1.9%). The curves obtained showed the materials to follow classic diffusion theory, with an initial linearity with respect to t(1/2) making it possible to calculate the diffusion coefficients. This showed iohexol to have the lowest diffusion coefficient, Palacos R the highest, and iodixanol close to that of Palacos R. The release study showed that more iohexol than iodixanol was released from the bone cement; the long-term release was above 25 microg/mL for iohexol compared to slightly above 10 microg/mL for iodixanol. A microCT investigation showed that the risk of developing an observable radiolucent zone is negligible.     

A radiopaque polymeric matrix for acrylic bone cements

As part of the search for an alternative to inorganic radiopaque agents, this work studies the possibility of modifying bone cement formulations by incorporating a radiopaque monomer, that is, 4-iodophenol methacrylate (IPMA), in the liquid phase. The monomer was synthesized in the laboratory, and cements were prepared by the standard method. The influence on the different cement characteristics of various monomer concentrations was studied. It was seen that the setting time decreased as the percentage of monomer increased. The radiopacity attained in the 15 vol.% IPMA formulations was about the same as that for a cement containing 10 wt.% barium sulphate. Dynamic and static mechanical properties were measured. The materials did not show significant differences in the glass transition temperature. However, static mechanical properties showed enhanced compressive strength, tensile strength, and elastic modulus with respect to conventional cements formulated with barium sulphate. Histological studies showed a good response of muscular tissue to implanted specimens.     

New injectable and radiopaque antibiotic loaded acrylic bone cements

The use of antibiotic loaded bone cements (ALBCs) has become a common clinical practice in the prevention and treatment of prosthesis-related infections. However, due to antibiotic resistance, there is a general interest in broadening the antibacterial spectrum of currently used drugs. The aim of this work is to formulate ALBCs for specific use in vertebroplasty and kyphoplasty, and to study the effect of the addition of ciprofloxacin alone and in combination with vancomycin on some properties of the cement. The cements were formulated using bismuth salicylate as the radiopacifier. The setting properties, residual monomer content, release of antibiotics, rheological behavior, injectability, and mechanical properties of these formulations were studied. They showed long setting times and low curing temperatures. From the release studies, antibacterial properties are assumed because the concentration of released antibiotic was higher than the minimum effective. Although the experimental cements had slightly reduced mechanical properties, the other alterations shown were negligible.     

Influence of the radiopacifier in an acrylic bone cement on its mechanical, thermal, and physical properties: barium sulfate-containing cement versus iodine-containing cement

In all acrylic bone cement formulations in clinical use today, radiopacity is provided by micron-sized particles (typical mean diameter of between about 1 and 2 microm) of either BaSO(4) or ZrO(2). However, a number of research reports have highlighted the fact that these particles have deleterious effects on various properties of the cured cement. Thus, there is interest in alternative radiopacifiers. The present study focuses on one such alternative. Specifically, a cement that contains covalently bound iodine in the powder (herein designated the I-cement) was compared with a commercially available cement of comparable composition (C-ment3), in which radiopacity is provided by BaSO(4) particles (this cement is herein designated the B-cement), on the basis of the strength (sigma(b)), modulus (E(b)), and work-to-fracture (U(b)), under four-point bending, plane-strain fracture toughness (K(IC)), Weibull mean fatigue life, N(WM) (fatigue conditions: +/-15 MPa; 2 Hz), activation energy (Q), and frequency factor (ln Z) for the cement polymerization process (both determined by using differential scanning calorimetry at heating rates of 5, 10, 15, and 20 K min(-1)), and the diffusion coefficient for the absorption of phosphate-buffered saline at 37 degrees C (D). For the B-cement, the values of sigma(b), E(b), U(b), K(IC), N(WM), Q, ln Z, and D were 53 +/- 3 MPa, 3000 +/- 120 MPa, 108 +/- 15 kJ m(-3), 1.67 +/- 0.02 MPa check mark m, 7197 cycles, 243 +/- 17 kJ mol(-1), 87 +/- 6, and (3.15 +/- 0.94) x 10(-12) m(2) s(-1), respectively. For the I-cement, the corresponding values were 58 +/- 5 MPa, 2790 +/- 140 MPa, 118 +/- 45 kJ m(-3), 1.73 +/- 0.11 MPa check mark m, 5520 cycles, 267 +/- 19 kJ mol(-1), 95 +/- 9, and (3.83 +/- 0.25) x 10(-12) m(2) s(-1). For each of the properties of the fully cured cement, except for the rate constant of the polymerization reaction, at 37 degrees C (k'), as estimated from the Q and ln Z results, there is no statistically significant difference between the two cements. k' for the I-cement was about a third that for the B-cement, suggesting that the former cement has a higher thermal stability. The influence of various characteristics of the starting powder (mean particle size, particle size distribution, and morphology) on the properties of the cured cements appears to be complex. When all the present results are considered, there is a clear indication that the I-cement is a viable candidate cement for use in cemented arthroplasties in place of the B-cement.     

Wear behaviour of the pair Ti-6Al-4V-UHMWPE of acrylic bone cements containing different radiopaque agents

The objective of this study was to improve the wear behaviour of acrylic bone cements by substituting the conventional inorganic radiopaque agents (BaSO(4), ZrO(2)) for different iodinated radiopaque monomers which can co-polymerize with the methyl methacrylate monomer, MMA. To this aim, the wear behaviour of the pair Ti-6Al-4V-UHMWPE (ultra high molecular weight polyethylene) was studied in the absence and in the presence of cement particles (the third body).     

Stress relaxation and creep behaviour of normal and carbon fibre reinforced acrylic bone cement

Room temperature compression creep and stress relaxation behaviour of normal as well as carbon fibre reinforced bone cement was studied and their properties compared. It was observed that increased deformation due to creep in 24 h was about 70% of the initial strain (due to applied constant stress of 10.5 MN/m²) for normal PMMA and this could be reduced to 45% of the initial strain by carbon fibre reinforcement. Surgical grade PMMA, when subjected to 1% constant strain, showed an average stress-relaxation by 24% in eight hours. Percentage of stress-relaxation was somewhat more for carbon fibre reinforced bone cement even though the level of stress was much higher compared to normal PMMA.     

Crack initiation processes in acrylic bone cement

A major constraint in improving the understanding of the micromechanics of the fatigue failure process and, hence, in optimizing bone cement performance is found in the uncertainties associated with monitoring the evolution of the internal defects that are believed to dominate in vivo failure. The present study aimed to synthesize high resolution imaging with complementary damage monitoring/detection techniques. As a result, evidence of the chronology of failure has been obtained. The earliest stages of crack initiation have been captured and it is proposed that, in the presence of a pore, crack initiation may occur away from the pore due to the combined influence of pore morphology and the presence of defects within regions of stress concentration. Furthermore, experimental evidence shows that large agglomerations of BaSO(4) are subject to microcracking during fatigue, although in the majority of cases, these are not the primary cause of failure. It is proposed that cracks may then remain contained within the agglomerations because of the clamping effect of the matrix during volumetric shrinkage upon curing.     

Mechanical properties of bone cement: a review

Many authors have examined the mechanical properties of bone cement and the various factors that affect its mechanical behavior. This article presents a comprehensive survey on the reported mechanical properties of bone cement. Variables that influence the mechanical properties, such as handling characteristics, strain rate, loading modes, additives, porosity, blood inclusion, in vivo environment, temperature, etc. have also been reviewed. The importance of specifying these variables in reporting test results on the mechanical properties of bone cement is pointed out. Previous attempts to improve the mechanical properties of bone cement are also summarized. Future research areas important for fully characterizing the physical properties of PMMA are also suggested.     

Degree of polymerization of acrylic bone cement.

Self-curing powder-liquid admixed acrylic systems are used for internal fixation fo total hip and total knee prostheses. Gel permeation chromatography revealed that the polymer chain length distributions of set cements were basically unaffected by their curing pressures. However, a decrease of approximately 11% in porosity coupled with a measured increase in mechanical strengths could be induced through the use of high curing pressures well beyond those attainable by the surgeon in the current arthroplasties. The conclusion of the investigation was that, to improve such cements, attention should be focused on elimination of porosity rather than attempting to produce higher degree of polymerization.     

Injectable acrylic bone cements for vertebroplasty based on a radiopaque hydroxyapatite. Bioactivity and biocompatibility

Radiopaque bone cements have been formulated to provide injectable pastes with improved bioactivity to be applied in vertebroplasty and kyphoplasty techniques. The bioactive compound was strontium containing hydroxyapatite salt, which was introduced as obtained (SrHA) or after treatment with MMA monomer (SrHA-t). The in vitro bioactivity of the cements was tested in cement films or in cement pastes introduced directly in a simulated body fluid (SBF) solution at 37 degrees C to mimic the in vivo conditions. Precipitation of an apatite-like layer was observed for the 20 wt %-SrHA-t containing cement in the first experiments, and in all formulations in the second ones. The deposited particles were characterized by FTIR spectroscopy and by EDAX analysis. Radiopacity of cements after immersion in SBF was confirmed. The biocompatibility exhibited by the SrHA containing cements was, in some cases, superior to that shown by a formulation with 10 wt % of BaSO(4). The new formulations prepared with the treated filler exhibited the lowest cytotoxicity and enhanced cellular proliferation. The in vivo biocompatibility tested by an intramuscular model in rats indicated the formation of a membrane formed by collagen fibers containing fibroblasts with no inflammatory cells, such as macrophages, giant cells or lymphocytes in all formulations.     

Microtomography assessment of failure in acrylic bone cement

Micromechanical studies of fatigue and fracture processes in acrylic bone cement have been limited to surface examination techniques and indirect signal analysis. Observations may then be mechanically unrepresentative and/or affected by the presence of the free surface. To overcome such limiting factors the present study has utilised synchrotron X-ray microtomography for the observation of internal defects and failure processes that occurred within a commercial bone cement during loading. The high resolution and the edge detection capability (via phase contrast imaging) have enabled clear microstructural imaging of both strongly and weakly absorbing features, with an effective isotropic voxel size of 0.7 microm. Detailed assessment of fatigue damage processes in in vitro fatigue test specimens is also achieved. Present observations confirm a link with macroscopic failure and the presence of larger voids, at which crack initiation may be linked to the mechanical stress concentration set up by adjacent beads at pore surfaces. This study does not particularly support the suggested propensity for failure to occur via the inter-bead matrix; however crack deflections at matrix/bead interfaces and the incidence of crack arrest within beads do imply locally increased resistance to failure and potential improvements in global crack growth resistance via crack tip shielding.     

Elimination of barium sulphate from acrylic bone cements. Use of two iodine-containing monomers

The aim of this work is to present a new approach to joint arthroplasty failure related to bone cement mantle. As barium sulphate is considered one of the main causes of mechanical weakness in the cement, we substituted this inorganic radiopacifier of the solid component for radiopaque monomers in the liquid component. We obtained two different cements, one containing 5 vol% 2-[2',3',5'-triiodobenzoyl] ethyl methacrylate (TIBMA) and the other containing 3,5-diiodine salicylic methacrylate (DISMA). In both cases, the mechanical properties of these new cements were better than those of the barium sulphate-containing cement. The radiopacity obtained was comparable to that of the aforementioned cement and all the samples showed good biocompatibility.     

Influence of the modification of P/L ratio on a new formulation of acrylic bone cement

The use of smaller powder/liquid (P/L) ratio favours the handling and wetting of poly(methyl methacrylate) (PMMA) beads in bone cement formulations. In this paper a P/L ratio of 1.86 is tested to overcome adhesion problems found in hydroxypropyl methacrylate (HPMA) modified bone cements and the influence on bone cement characteristics was analysed. The reduction of the P/L ratio leads to higher temperature peaks and shorter setting times, whereas the residual monomer content increases slightly. Water uptake obeys the diffusion laws, and the introduction of a more hydrophilic monomer gives rise to an increase of this parameter, which does not present significant changes with modification of the P/L ratio. Polymerization shrinkage is slightly greater because of the introduction of higher proportions of monomer in the formulation. Mechanical properties are similar to those obtained with conventional P/L ratios. The analysis of scanning electron microscopy (SEM) reveals an improvement of the adhesion between phases with respect to P/L = 2 formulations.     

Preparation of acrylic bone cements for vertebroplasty with bismuth salicylate as radiopaque agent

One of the problems of percutaneous vertebroplasty attributed to the use of acrylic cements is related to the radiopacity of the formulation. The use of bismuth salicylate as the radiopaque agent is proposed in this work, taking into account the high radiopacity of organobismuth compounds used in dental applications and the possible analgesic effect of salicylic acid. Various cements formulated with this compound (some of them modified with polyethylene oxide) were examined. Setting parameters, mechanical properties, rheological behaviour, injectability, radiopacity and biocompatibility were studied for a variety of formulations, showing that the cement formulations containing bismuth salicylate have a higher radiopacity and better injection properties than commercial bone cement preparations and present good mechanical properties.     

Slow crack growth in acrylic bone cement.

Slow crack growth in Perspex acrylic sheet (PMMA) and Simplex acrylic bone cement in air and water has been studied from a fracture mechanics viewpoint. It has been found that the crack velocity, V, for each material depends upon the intensification of stress at the tip of the crack. Experimental measurements have been made of V as a function of the stress intensity factor, K, at the crack tip, and a derived V, K relationship has been used to predict the times-to-failure of components made from PMMA and Simplex cement. Direct measurements of time-to-failure for PMMA have shown that the predicted values give a conservative estimate of the structural lifetime of the material.     

A proposed specification for acrylic bone cement.

A proposed specification covering handling characteristics and physical and chemical properties of bone cement composed primarily of methyl methacrylate has been prepared on the basis of data from the authors' studies and from various other sources. Under handling characteristics, requirements included relate to dough, handling and setting time, proper plasticity for insertion and temperature rise on setting. Mechanical properties specified include compressive strength and indentation and recovery characteristics. Maximum limits are proposed for water sorption and solubility. Suggested packaging requirements are also included.