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.     

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.     

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.     

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).     

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.     

Injectable acrylic bone cements for vertebroplasty with improved properties

Currently commercially available acrylic bone cements lack adequate radiopacity and viscosity when they are used in percutaneous vertebroplasty (PVP). In this work improved formulations of radiopaque and injectable poly(methyl methacrylate) bone cements were prepared with different amounts (10-50 wt.%) of BaTiO3 or SrTiO3 particles as the radiopaque agent. Two sets of cements were prepared by using untreated or silanated radiopaque particles, respectively. The influence of the content and nature of the radiopaque agent as well as its silanation with 3-(trimethoxysilyl) propyl methacrylate (gamma-MPS), on the curing parameters, residual monomer content, radiopacity, mechanical properties, and injectability of the resulting materials, was examined. Doughing and setting times, maximum temperature, and compressive strength of all formulations fulfilled the requirements of standard specifications, with values of peak temperature in the range 57-72 degrees C and those of compressive strength between 114 and 135 MPa. Formulations containing at least 20 wt.% BaTiO3 or SrTiO3 had radiopacities equal to or greater than that corresponding to 2 mm of Al as required for surgical plastics. Injectability of any of the formulations provided 75-80 wt.% of the total mass manually injected through a conventional biopsy needle 4 min after mixing. Silanation of the BaTiO3 or SrTiO3 particles led to formulations with improved mechanical properties and injectability compared to those obtained with the untreated fillers.     

Selection of acrylic bone cements for use in joint replacement

Commercial acrylic bone cements have been compared in terms of their mechanical, thermal and rheological properties. Significant differences have been found between the tensile strengths, shear strengths and peak polymerization temperatures of the cements tested. Large differences have been found between the viscosities of different formulations and the duration of their working periods during polymerization. Optimum cement selection is found to depend critically upon ambient conditions within the operating theatre considered in combination with the characteristics of the cements themselves. It is proposed that, at present, the only differences between commercial bone cements of relevance to successful joint replacement lie in the area of rheological properties during polymerization.     

Mechanical behaviour of a new acrylic radiopaque iodine-containing bone cement

In total hip replacement, fixation of a prosthesis is in most cases obtained by the application of methacrylic bone cements. Most of the commercially available bone cements contain barium sulphate or zirconium dioxide as radiopacifier. As is shown in the literature, the presence of these inorganic particles can be unfavourable in terms of mechanical and biological properties. Here, we describe a new type of bone cement, where X-ray contrast is obtained via the introduction of an iodine-containing methacrylate copolymer; a copolymer of methylmethacrylate and 2-[4-iodobenzoyl]-oxo-ethylmethacrylate (4-IEMA) is added to the powder component of the cement. The properties of the new I-containing bone cement (I-cement) are compared to those of a commercially available bone cement, with barium sulphate as radiopacifier (B-cement). The composition of the I-cement is adjusted such that similar handling properties and radiopacity as for the commercial cement are obtained. In view of the mechanical properties, it can be stated that the intrinsic mechanical behaviour of the I-cement, as revealed from compression tests, is superior to that of B-cement. Concerning the fatigue behaviour it can be concluded that, though B-cement has a slightly higher fatigue crack propagation resistance than I-cement, the fatigue life of vacuum-mixed I-cement is significantly better than that of B-cement. This is explained by the presence of BaSO4 clumps in the commercial cement; these act as crack initiation sites. The mechanical properties (especially fatigue resistance) of the new I-cement warrant its further development toward clinical application.     

Properties of acrylic bone cements formulated with Bis-GMA

Experimental cement formulations were prepared by replacing part of the methylmethacrylate (MMA) liquid phase of a conventional surgical cement with an equivalent weight of 2,2-bis [4(2-hydroxy-3-methacryloxypropoxy) phenyl] propane (Bis-GMA), which is the reaction product of diglycidyl ether of bisphenol A and methacrylic acid. It was found that up to 50 wt % of the MMA could be replaced by Bis-GMA without reductions in flow characteristics of the precured polymers. Cements containing 20, 30, 40, and 50 wt % of Bis-GMA in the liquid component were prepared. Over this range of Bis-GMA wt %, it was found that, relative to the unmodified cement, the volumetric shrinkage (DV), the peak temperature reached during the polymerization reaction (Tp), and the flexural strength (obtained in three-point bend tests) were each significantly reduced, the flexural modulus (obtained in three-point bend tests) increased significantly, the compressive strength increased slightly, while there were no significant effects on any of the other properties determined, namely, degree of conversion of the monomer during the polymerization reaction and the glass transition temperature. The drops in D(V) and Tp indicate that cements whose liquid monomers are modified using Bis-GMA hold promise for use in anchoring total joint replacements. The increase in the crosslinking density with increasing amount of Bis-GMA renders the polymer matrix more brittle. This feature was considered responsible for the reduced flexural strength.     

Tensile characteristics of ten commercial acrylic bone cements

The mechanical properties of acrylic bone cement, used in orthopedic surgery, are very influential in determining successful long-term stability of a prosthesis. A large number of commercial formulations are available, differing in chemical composition and physical properties of both powder and monomer constituents. In this study, the static and dynamic tensile characteristics of a number of the most commonly used bone cements (Palacos R, Simplex P, CMW 1 & 3, Sulfix-60, Zimmer Dough), along with some newer formulations (Endurance, Duracem 3, Osteobondtrade mark and Boneloc), have been investigated under the same testing regimes. Testing was performed in air at room temperature. Significant differences in both static and fatigue properties were found between the various bone cements. Tensile tests revealed that Palacos R, Sulfix-60, and Simplex P had the highest values of ultimate tensile strength, closely followed by CMW 3, while Zimmer Dough cement had the lowest strength. Fatigue testing was performed under stress control, using sinusoidal loading in tension-tension, with an upper stress level of 22MPa. The two outstanding cements when tested in these cyclic conditions were Simplex P and Palacos R, with the highest values of Weibull median cycles to failure. Boneloc bone cement demonstrated the lowest cycles to failure. While the testing regimes were not designed to replicate exact conditions experienced by the bone cement mantle in vivo, there was a correlation between these results and clinical outcome.     

Contact killing antimicrobial acrylic bone cements: preparation and characterization

Novel antimicrobial poly(methyl methacrylate) (PMMA)-based bone cement was synthesized by co-polymerizing PMMA/MMA with various percentages of quaternary amine dimethacrylate (QADMA) by free radical bulk polymerization technique at room temperature using benzoyl peroxide and N, N-dimethyl-p-toulidine (DMPT) as a redox initiator. The modified bone cement was characterized by FT-IR and ¹H-NMR spectral studies. The thermal and physical properties of the bone cements of varying composition of QADMA were evaluated by thermogravimetric analysis (TGA), differential calorimetry (DSC) and contact angle measurements. Peak exothermic temperature was observed to decrease, while setting time increased with increase in QADMA content in the bone cement formulations. The antibacterial activity of the synthesized bone cement containing quaternary amine dimethacrylate against Escherichia coli and Staphylococcus aureus was studied by zone of inhibition, colony count method and scanning electron microscopy (SEM). QADMA containing acrylic bone cement showed a broad spectrum of contact killing antimicrobial properties. Retention of E. coli onto the surface of PMMA bone cement was observed, whereas there was complete prevention of retention of E. coli onto the modified PMMA bone cement with 15% QADMA. The studies were compared with the acrylic bone cement synthesized using 15% N-vinyl-2-pyrrolidone (NVP) in place of QADMA to which iodine was added as an antimicrobial agent during co-polymerization.     

Contact killing antimicrobial acrylic bone cements: preparation and characterization

Novel antimicrobial poly(methyl methacrylate) (PMMA)-based bone cement was synthesized by co-polymerizing PMMA/MMA with various percentages of quaternary amine dimethacrylate (QADMA) by free radical bulk polymerization technique at room temperature using benzoyl peroxide and N,N-dimethyl-p-toulidine (DMPT) as a redox initiator. The modified bone cement was characterized by FT-IR and 1H-NMR spectral studies. The thermal and physical properties of the bone cements of varying composition of QADMA were evaluated by thermogravimetric analysis (TGA), differential calorimetry (DSC) and contact angle measurements. Peak exothermic temperature was observed to decrease, while setting time increased with increase in QADMA content in the bone cement formulations. The antibacterial activity of the synthesized bone cement containing quaternary amine dimethacrylate against Escherichia coli and Staphylococcus aureus was studied by zone of inhibition, colony count method and scanning electron microscopy (SEM). QADMA containing acrylic bone cement showed a broad spectrum of contact killing antimicrobial properties. Retention of E. coli onto the surface of PMMA bone cement was observed, whereas there was complete prevention of retention of E. coli onto the modified PMMA bone cement with 15% QADMA. The studies were compared with the acrylic bone cement synthesized using 15% N-vinyl-2-pyrrolidone (NVP) in place of QADMA to which iodine was added as an antimicrobial agent during co-polymerization.     

Mechanical performance of acrylic bone cements containing different radiopacifying agents

The effect that three different radiopacifying agents, two of them inorganic (BaSO4, ZrO2) and one organic (an iodine containing monomer, IHQM) have on the static and dynamic mechanical properties of acrylic bone cements was studied. Compressive and tensile strength, fracture toughness and fatigue crack propagation were evaluated. The effect of the inorganic fillers depends on their size and morphology. In relation to the radiolucent cement, the addition of zirconium dioxide improved significantly the tensile strength, the fracture toughness and the fatigue crack propagation resistance. In contrast, the addition of barium sulphate produced a decrease of the tensile strength, but did not affect the fracture toughness and improved the crack propagation resistance. When the iodine containing monomer was used, although the tensile strength and the fracture toughness increased, the fatigue crack propagation resistance remained as low as it was for the radiolucent cement.     

Characterization of new acrylic bone cements prepared with oleic acid derivatives

Acrylic bone-cement formulations were prepared with the use of a new tertiary aromatic amine derived from oleic acid, and also by incorporating an acrylic monomer derived from the same acid with the aim of reducing the leaching of toxic residuals and improving mechanical properties. 4-N,N dimethylaminobenzyl oleate (DMAO) was used as an activator in the benzoyl-peroxide radical cold curing of polymethyl methacrylate. Cements that contained DMAO exhibited much lower polymerization exotherm values, ranging between 55 and 62 C, with a setting time around 16--17 min, depending on the amine/BPO molar ratio of the formulation. On curing a commercial bone cement, Palacosreg R with DMAO, a decrease of 20 C in peak temperature and an increase in setting time of 7 min were obtained, the curing parameters remaining well within limits permitted by the standards. In a second stage, partial substitution of MMA by oleyloxyethyl methacrylate (OMA) in the acrylic formulations was performed, the polymerization being initiated with the DMAO/BPO redox system. These formulations exhibited longer setting times and lower peak temperatures with respect to those based on PMMA. The glass transition temperature of the experimental cements were lower than that of PMMA cement because of the presence of long aliphatic chains of both activator and monomer in the cement matrix. Number average molecular weights of the cured cements were in the range of 1.2x10(5). PMMA cements cured with DMAO/BPO revealed a significant (p<0.001) increase in the strain to failure and a significant (p<0.001) decrease in Young's modulus in comparison to Palacosreg R, whereas ultimate tensile strength remained unchanged. When the monomer OMA was incorporated, low concentrations of OMA provided a significant increase in tensile strength and elastic modulus without impairing the strain to failure. The results demonstrate that the experimental cements based on DMAO and OMA have excellent promise for use as orthopaedic and/or dental grouting materials.     

Gentamicin release from modified acrylic bone cements with lactose and hydroxypropylmethylcellulose

Modified polymethylmethacrylate (PMMA) bone cements formulations were prepared by including different proportions of gentamicin and release modulators such as lactose or hydroxypropylmethylcellulose (HPMC). Surface aspect, gentamicin release and porosity of these modified formulations were studied by means of scanning electron microscopy (SEM), a specially designed system for the dissolution studies of the bone cements, and mercury intrusion porosimetry. Lactose modified cements presented an irregular surface with numerous hollows and voids due to the lactose dissolution. HPMC cements presented a characteristic laminated and flaky surface. The drug release of lactose formulations was up to four-fold greater (13%) than the commercial bone cement CMW1 Gentamicin one (3%). The amount of gentamicin eluted at the first withdrawn sample ranged from 30% to 60% of total gentamicin released over the assay. Gentamicin release from lactose formulations increased as lactose percentage was increased which agree with the porosity results. Nevertheless, the use of release modulator HPMC increased porosity, but did not produce an increase in the gentamicin release. HPMC dissolution creates a surrounding sticky and viscous medium similar to a gel that makes the gentamicin release from the cement matrix difficult.     

Improved fatigue life of acrylic bone cements reinforced with zirconia fibers

Poly(methyl methacrylate) (PMMA) bone cements have a long and successful history of use for implant fixation, but suffer from a relatively low fracture and fatigue resistance which can result in failure of the cement and the implant. Fiber or particulate reinforcement has been used to improve mechanical properties, but typically at the expense of the pre-cured cement viscosity, which is critical for successful integration with peri-implant bone tissue. Therefore, the objective of this study was to investigate the effects of zirconia fiber reinforcement on the fatigue life of acrylic bone cements while maintaining a relatively low pre-cured cement viscosity. Sintered straight or variable diameter fibers (VDFs) were added to a PMMA cement and tested in fully reversed uniaxial fatigue until failure. The mean fatigue life of cements reinforced with 15 and 20 vol% straight zirconia fibers was significantly increased by ～40-fold, on average, compared to a commercial benchmark (Osteobond?) and cements reinforced with 0–10 vol% straight zirconia fibers. The mean fatigue life of a cement reinforced with 10 vol% VDFs was an order of magnitude greater than the same cement reinforced with 10 vol% straight fibers. The time-dependent viscosity of cements reinforced with 10 and 15 vol% straight fibers was comparable to the commercial benchmark during curing. Therefore, the addition of relatively small amounts of straight and variable diameter zirconia fibers was able to substantially improve the fatigue resistance of acrylic bone cement while exhibiting similar handling characteristics compared to current commercial products.     

Platelet activation after in vitro contact with seven acrylic bone cements

Seven acrylic bone cements were evaluated: Cemex Rx (Tecres S.p.a., Italy), Cemex Isoplastic (Tecres S.p.a., Italy), Zimmer Low Viscosity Cement (L.V.C., Zimmer, IN, USA), Zimmer bone cement - dough type (Zimmer, IN, USA), CMW (DePuy International Ltd., UK), Cerim LT (Cremascoli S.r.l., Italy), and Palacos (Merck, Wehreim, Germany). The cements after polymerization were put in contact in vitro with platelet-rich plasma. Plasma in contact only with siliconated glass was used as the negative control. After contact, platelet number, beta-thromboglobulin (beta-TG), and transforming growth factor-beta1 (TGF-beta1) were determined. The Wilcoxon signed rank test showed Palacos R and L.V.C. induced a significant decrease of platelet number compared with the negative control. All cements determined a significant increase in beta-TG. CMW 3, Palacos, L.V.C., and Zimmer dough type determined a significant increase in TGF-beta1 compared with the negative control.     

Platelet activation after in vitro contact with seven acrylic bone cements

Seven acrylic bone cements were evaluated: Cemex Rx (Tecres S.p.a., Italy), Cemex Isoplastic (Tecres S.p.a., Italy), Zimmer Low Viscosity Cement (L.V.C. , Zimmer, IN, USA), Zimmer bone cement—dough type (Zimmer, IN, USA), CMW 3 (DePuy International Ltd., UK), Cerim LT (Cremascoli S.r.l., Italy), and Palacos R (Merck, Wehreim, Germany). The cements after polymerization were put in contact in vitro with platelet-rich plasma. Plasma in contact only with siliconated glass was used as the negative control. After contact, platelet number, β-thromboglobulin (β-TG), and transforming growth factor-β1 (TGF-β1) were determined. The Wilcoxon signed rank test showed Palacos R and L.V.C. induced a significant decrease of platelet number compared with the negative control. All cements determined a significant increase in β-TG. CMW 3 , Palacos , L.V.C. , and Zimmer dough type determined a significant increase in TGF-β1 compared with the negative control.