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Prevention of infection with tobramycin-containing bone cement or systemic cefazolin in an animal model.

We investigated in an animal model the efficacy of tobramycin-containing bone cement and systemic cefazolin for infection prophylaxis. In 18 female rabbits, the femoral cavity was inoculated with Staphylococcus aureus before injection of bone cement. The first group of six rabbits received tobramycin-containing Simplex-P bone cement. Two other groups of six rabbits received plain Simplex-P bone cement. Preoperatively, in one of the two latter groups cefazolin was administered intravenously. The other group served as untreated controls. The rabbits were monitored for clinical signs of infection. At 7 days' follow-up, the femora were harvested and cultures from the bone adjacent to the cement plug were quantified. Cultures from the rabbits which received antibiotic prophylaxis (either cefazolin systemically or tobramycin-containing bone cement) were all negative. In contrast, all rabbits in the untreated control group had positive cultures. These rabbits also had other signs of infection such as an elevated erythrocyte sedimentation rate and loss of body weight. Culture results were confirmed by the absence of bacterial DNA in the polymerase chain reaction hybridization assay. In conclusion, we found that both tobramycin-containing bone cement and systemic cefazolin are effective in preventing implant bed infection in rabbits up to 7 days after contamination with S. aureus.

Animals↗

Mechanical strength of the cement-bone interface is greater in shear than in tension.

The objective of this study was to determine the relative mechanical properties of the cement-bone interface due to tensile or shear loading. Mechanical tests were performed on cement-bone specimens in tensile (n = 51) or shear (n = 55) test jigs under the displacement control at 1 mm/min until complete failure. Before testing, the quantity of bone interdigitated with the cement was determined and served as a covariate in the study. The apparent strength of the cement-bone interface was significantly higher (p < 0.0001) for the interface when loaded in shear (2.25 MPa) when compared to tensile loading (1.35 MPa). Significantly higher energies to failure (p < 0.0001) and displacement before failure (p < 0.01) were also determined for the shear specimens. The post-yield softening response was not different for the two test directions. The data obtained herein suggests that cement-bone interfaces with equal amounts of tensile and shear stress would be more likely to fail under tensile loading.

Adult↗

Effect of bioactive filler content on mechanical properties and osteoconductivity of bioactive bone cement.

We took three types of bioactive bone cement (designated AWC, HAC, and TCPC), each with a different bioactive filler, and evaluated the influence of each filler on the mechanical properties and osteoconductivity of the cement. The cements consisted of bisphenol-a-glycidyl methacrylate-based (Bis-GMA based) monomers as an organic matrix, with a bioactive filler of apatite/wollastonite containing glass-ceramic (AW-GC) or sintered hydroxyapatite (HA) or beta-tricalcium phosphate (beta-TCP) powder. Each filler was mixed with the monomers in proportions of 50, 70, and 80% (w/w), giving a total of nine cement subgroups. The nine subgroups were designated AWC50, AWC70, AWC80, HAC50, HAC70, HAC80, TCPC50, TCPC70, and TCPC80. The compressive and bending strengths of AWC were found to be higher than those of HAC and TCPC for all bioactive filler contents. We also evaluated the cements in vivo by packing them into the intramedullary canals of rat tibiae. To compare the osteoconductivity of the cements, an affinity index was calculated for each cement; it equaled the length of bone in direct apposition to the cement, expressed as a percentage of the total length of the cement surface. Microradiographic examination up to 26 weeks after implantation revealed that AWC showed a higher affinity index than HAC and TCPC for each filler content although the affinity indices of all nine subgroups (especially the AWC and HAC subgroups) increased with time. New bone had formed along the AWC surface within 4 weeks, even in the cement containing AW-GC filler at only 50% (w/w); observation of the cement-bone interfaces using a scanning electron microscope showed that all the cements had directly contacted the bone. At 4 weeks the AWC had bonded to the bone via a 10 micron-thick reactive layer; the width of the layer, in which partly degraded AW-GC particles were seen, became slightly thicker with time. On the other hand, in the HAC- and TCPC-implanted tibiae, some particles on the cement surface were surrounded by new bone and partly absorbed or degraded. The results suggest that the stronger bonding between the inorganic filler and the organic matrix in the AWC cements gave them better mechanical properties. The results also indicate that the higher osteoconductivity of AWC was caused by the higher reactivity of the AW-GC powder on the cement surface.

Animals↗

Antibiotic-acrylic bone cement composites. Studies of gentamicin and Palacos.

Palacos bone cement with and without contained gentamicin was tested for antibacterial efficacy using a rabbit model of a knee hemiarthroplasty and a challenge with intra-articular Escherichia coli. The gentamicin-containing cement prevented infection from challenge with Escherichia coli and protected against inadvertent operative infection as well. Antibiotic concentrations in synovial fluid and urine remained in the therapeutic range for three days, whereas levels in serum were always quite low. Eight per cent of the gentamicin had leached out of the bone cement by eight days, most of it during the first day. Thereafter, extremely small amounts of gentamicin left the cement on a daily basis. The amount of antibiotic leaching out in vitro was proportional to the surface area of the cement. More eluted into serum than into saline.

Animals↗

Bioactive bone cement: comparison of apatite and wollastonite containing glass-ceramic, hydroxyapatite, and beta-tricalcium phosphate fillers on bone-bonding strength.

A study was conducted to compare the bone-bonding strengths of three types of bioactive bone cement, consisting of either apatite- and wollastonite-containing glass-ceramic (AW-GC) powder, hydroxyapatite (HA) powder, or beta-tricalcium phosphate (beta-TCP) powder as an inorganic filler and bisphenol-a-glycidyl methacrylate (Bis-GMA) based resin as an organic matrix. Seventy percent (w/w) filler was added to the cement. Rectangular plates (10 x 15 x 2 mm) of each cement were made and abraded with #2000 alumina powder. After soaking in simulated body fluid for 2 days, the AW cement (AWC) and HA cement (HAC) formed bonelike apatite over their entire surfaces, but the TCP cement (TCPC) did not. Plates of each type of cement were implanted into the tibial metaphyses of male Japanese white rabbits, and the failure loads were measured by a detaching test at 10 and 25 weeks after implantation. The failure loads of AWC, HAC, and TCPC were 3.95, 2.04, and 2.03 kgf at 10 weeks and 4.36, 3.45, and 3.10 kgf at 25 weeks, respectively. The failure loads of the AWC were significantly higher than those of the HAC and TCPC at 10 and 25 weeks. Histological examination by contact microradiogram and Giemsa surface staining of the bone-cement interface revealed that all the bioactive bone cements were in direct contact with bone. However, scanning electron microscopy and energy-dispersive X-ray microanalysis showed that only AWC had contacted to the bone via a Ca-P rich layer formed at the interface between the AW-GC powder and the bone, which might explain its high bone-bonding strength. Neither the HAC nor the TCPC contacted the bone through such a layer between each powder and the bone, although the HAC and TCPC directly contacted with bone. Our results indicate that all three types of abraded and prefabricated cement have bonding strength to bone, but AWC has superior bone-bonding strength compared to HAC and TCPC.

Animals↗

[Mechanical properties of new low viscosity bone cements--can be improved by vacuum mixing].

With the objective of improving mechanical properties by using a new catalyst, a new bone cement (Sulfix-60) and a new low-viscosity cement with added gentamycin (Allofix-G) were developed. Dynamic weakness was the major disadvantage of the older Sulfix-6 cement, especially in comparison with high-viscosity bone cement. Although static strength could be improved, investigations into improved fatigue strength and the effect of vacuum-mixing on the static and fatigue strength had yet to be carried out. To investigate fatigue stability specimens of the new bone cements were tested using loads under wet conditions until breakage or 20 million cycles. In a first series the cement was hand-mixed in a second series vacuum-mixed alone, and in a third series vacuum-mixed under pressure. Additionally, the ultimate static bending strength was investigated using the standard four-point bending test for the three series of bone cement. Vacuum-mixing brought about an improvement in the dynamic strength of Sulfix-60 from 6.3 MPa, to 9.1 MPa and for Allofix-G from 6.3 MPa to 8.2 MPa; additional pressure brought no further improvement. A 200% increased fatigue stability was detectable in comparison with the older cement. The ultimate bending strength was also significantly improved by vacuum-mixing for both bone cements.

Biomechanical Phenomena↗

Immunological responsiveness of guinea pigs to antibiotics diffusing from bone cement.

The sustained release of antibiotics from bone cement provides an opportunity for the induction of hypersensitivity. We evaluated the cellular and humoral immune responsiveness of guinea pigs to antibiotics diffusing from bone cement. We were unable to detect the presence of antibodies or skin hypersensitivity to any of the antibiotics tested.

Animals↗

[Effect of pedicle screw fixation with bone cement in lumbar].

OBJECTIVE: To evaluate the strength of pedicle screw fixation with bone cement in human cadaveric lumbar vertebral bodies by using biomechanical test. METHODS: Twenty-four fresh frozen cadaveric lumbar vertebral bodies were randomly divided into 3 groups, which each group had 8 bodies. The bodies in the first group were drilled only. The bodies in the second group were drilled with tap. The bodies in the third group were drilled and the holes were enlarged by borer. Each vertebral body was drilled in both right and left sides, which one side served as control with the pedicle screws fixation only and another side served as testing side with the pedicle screw fixation with bone cement. The pullout strength was tested on both sides by using borer. RESULT: There was significant difference of manifestation of pull-strength between the control side and the testing side in all groups (P < 0.001). For the manifestation of pull-strength of testing side in different groups, which had pedicle screw fixation with bone cement, there was no significant difference between the second group and third group, however, the difference between the first group and the second group and between the first group and third group were significant. CONCLUSION: The pedicle screws with bone cements could significantly enhance the strength of fixation in cadaveric lumbar compared with pedicle screws only.

Bone Cements↗

[Radioactivity of bone cement].

A total of 14 samples of different types of bone cement from five different manufacturers were examined for their radioactivity. Each of the investigated bone cements showed a low radioactivity level, i.e. between < 1 and 100 Bq/kg. The content of U-238 and K-40 always was below the limit of detection (< 1-< 10 Bq/kg). Significant differences were detected in the amount of Ra-226, Pb-210, and Ra-228 detected between different samples of the same product from the same manufacturer, as well as between various types of cements. The highest radioactivity level was measured for Ra-226. Although stochastic radiation effects can not totally be excluded, it is extremely unlikely that the small amount of radioactive substances additionally transferred into the body by the bone cement has negative effects on the recipient's organism or on the fate of the alloplastic implant: "The risk factor and extrapolation in a low dosage range ... do not lead to an underestimation but more likely to an overestimation of the radiation hazard" [18].

Bone Cements↗

A procedure and criterion for bone cement fracture toughness tests.

Nowadays, two procedures, based on the recommendation of two American standards (ASTM E399 and ASTM D5045), are used to determine the fracture toughness, KIc, of bone cement. However, there is a lack of knowledge about the equivalence of the two testing methods applied to bone cement. Additionally, in spite of the recommendation of several authors to introduce a rejection criterion for specimens based on the size of defects found in the fracture surface, no data are available about the effect of porosity within the material on the KIc of bone cement. The aims of this study were to verify whether the KIc values calculated for bone cement using the two procedures are comparable and whether macroporosity within the tested samples affects the KIc value of bone cement, and, if so, to establish a rejection criterion for specimen selection. Samples of pure polymethyl methacrylate (PMMA) were tested by both procedures. Additionally, samples showing defects (macroporosity) of different sizes and located in different positions within the specimen were tested. The KIc value determined following the ASTM E399 procedure was 13 per cent lower than that calculated following the ASTM D5045 procedure. In the first series a lower data scatter was observed. Also, the presence of macroporosity on the fracture surface of the specimen affected the KIc value of bone cement. Therefore, the mechanical behaviour of samples was affected by defects within the material. Since it is possible to mould specimens without macroporosity, it seems recommendable to reject specimens with macroporosity on the fracture surface before calculating the KIc value of bone cement.

Bone Cements↗

Ingrowth of bone into absorbable bone cement: an in vivo microscopic evaluation.

The purpose of the study reported here was to use an in vivo rabbit model to evaluate the rate of bone ingrowth into remodelable calcium phosphate bone cement. We evaluated an in vivo bone chamber placed in a rabbit tibia with its ingrowth compartment filled with absorbable calcium phosphate bone cement (Norian Skeletal Repair System; Norian Corp, Cupertino, Calif). Five New England white rabbits had a single bone chamber implanted into the proximal right tibia. Observations were made and photomicrographs taken on a weekly basis. Results of morphological analysis showed sequential loss of cement and subsequent bone ingrowth over a testing period of up to 30 weeks. Resorption of bone cement was complete in 1 rabbit. The other rabbits had significant bone ingrowth, which reaffirms the biocompatibility of this material. Results of this study showed that using in vivo microscopy with the rabbit bone chamber model was useful in evaluating bone ingrowth and replacement of absorbable bone cement. This model may make it possible to evaluate various combinations of bone cement and bone growth factors, which could serve as an alternative to autogenous bone grafting.

Animals↗

Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation.

We measured the formation of a Staphylococcus aureus biofilm in vitro on unloaded and gentamicin-loaded bone cements (CMW3 and Palacos R) and related the formation to antibiotic release rates. All experiments were done in triplicate. Microbial growth on gentamicin-loaded cements occurred despite the release of antibiotic. Biofilm formation on gentamicin loaded CMW3 bone cement was one fourth to one fifth less than on the unloaded bone cement, while biofilm formation on Palacos R bone cement was not significantly affected by antibiotic loading. More gentamicin was released from CMW3 (79 mg) than from Palacos R (70 mg), but the percentage gentamicin released after one week relative to the total amount incorporated was significantly lower for CMW3 (4.7%) than for Palacos R (8.4%). After one day, subinhibitory concentrations of antibiotics were eluted from the cements. We concluded that antibiotic-loaded bone cement does not necessarily inhibit the formation of an infectious biofilm in vitro.

Anti-Bacterial Agents↗

Characterization of acrylic bone cement using dynamic mechanical analysis.

Dynamic mechanical analysis (DMA) was used to characterize the properties of acrylic bone cement with the addition of tricalcium phosphate (TCP), hydroxyethyl methacrylate (HEMA), and ethylene glycol dimethacrylate (EGDMA). The glass transition temperature of acrylic bone cement is >100 degrees C; the cement has a flat modulus response near human body temperature. The height of the damping peak decreases and becomes broader with increasing TCP content. Thus, TCP is incompatibile with acrylic bone cement. When the frequency is changed from high to low, the damping peak shifts to low temperature. The shift in damping peak with frequency indicates that this relaxation is time-dependent. When acrylic bone cement contains TCP with HEMA and EGDMA, the incompatibility between acrylic bone cement and TCP can be ameliorated.

Biocompatible Materials↗

Bacterial survival in the interfacial gap in gentamicin-loaded acrylic bone cements.

Clinical experience indicates the beneficial effects of antibiotic-loaded bone cement. Although in vitro studies have shown the formation of a biofilm on its surface they have not considered the gap between the cement and the bone. We have investigated bacterial survival in that gap. Samples with gaps 200 microm wide were made of different bone cements. These were stored dry ('pre-elution') or submersed in phosphate-buffered saline to simulate the initial release of gentamicin ('post-elution'). The gaps were subsequently inoculated with bacteria, which had been isolated from infected orthopaedic prostheses and assessed for their sensitivity to gentamicin. Bacterial survival was measured 24 hours after inoculation. All the strains survived in plain cements. In the pre-elution gentamicin-loaded cements only the most gentamicin-resistant strain, CN5115, survived, but in post-elution samples more strains did so, depending on the cement tested. Although high concentrations of gentamicin were demonstrated in the gaps only the gentamicin-sensitive strains were killed. This could explain the increased prevalence of gentamicin-resistant infections which are seen clinically.

Anti-Bacterial Agents↗

Biodegradable bone cement compositions based on acrylate and epoxide terminated poly(propylene fumarate) oligomers and calcium salt compositions.

The synthesis of biodegradable bone cement compositions is presented. These bone cement compositions can be applied as a putty-like mixture and harden to a strong material in a bone fracture. They degrade from the site of application to allow the ingrowth of new bone for complete healing of the bone fracture. The bone cement is composed of a solid particulate phase dispersed in an initially liquid polymeric phase, which can be hardened by cross-linking. The polymeric phase is a low-molecular-weight liquid poly(propylene fumarate) (PPF) containing double bonds available for cross-linking. The solid particulate phase consists of calcium carbonate and tricalcium phosphate. PPF oligomers of Mw = 1800 and Mn = 750 were prepared from the condensation of non-volatile bis(2-hydroxypropyl fumarate) and propylene-bis(hydrogen maleate) trimers. PPF terminated divinyl and diepoxide derivatives were obtained from the reactions between PPF diol and acryloyl chloride or epichlorhydrin, respectively. Putty-like cement compositions were prepared from a mixture of 30 wt% polymer phase containing benzoyl peroxide-dimethyl toluidine as polymerization catalyst and 70 wt% calcium salts. The divinyl and diepoxide terminated PPF oligomers provided a high strength composition of between 30 and 129 MPa which is suitable for bone cement applications. In vitro hydrolysis of the composites showed little weight loss with the compressive strength remaining above 20 MPa after 4 weeks in buffer solution. Compositions of the PPF oligomers cross-linked without calcium salts showed a gradual weight loss (10-65 wt% after 4 weeks) when placed in buffer solution followed by high water absorption (18-200 wt% after 4 weeks), with the epoxide terminated PPF being the least to degrade or absorb water.

Acrylates↗

Bioactive PMMA bone cement prepared by modification with methacryloxypropyltrimethoxysilane and calcium chloride.

Bone cement consisting of polymethylmethacrylate (PMMA) powder and methylmethacrylate (MMA) liquid is used extensively for fixation of implants such as artificial hip joints with living bone. This type of cement, however, does not show direct bonding to the living body, and hence the fixation is liable to loosen over a long implantation period. Bioactive materials have received much attention because of their capability for bone-bonding, i.e., bioactivity, when implanted in bony defects. Osteoconduction of the bioactive materials is caused by formation of a bone-like apatite layer through a surface reaction between the material and surrounding body fluid. The apatite formation can be induced by a silanol (Sibond;OH) group formed on the materials as well as a dissolution of calcium ion (Ca(2+)) from the material. Incorporation of alkoxysilane and calcium chloride (CaCl(2)) may provide PMMA bone cement with bioactivity, because alkoxysilane gives Sibond;OH after hydrolysis, whereas CaCl(2) releases Ca(2+). In this study, we investigated the potential on bioactivity of the modified PMMA bone cement with alkoxysilane and calcium chloride. PMMA powder was mixed with various amounts of CaCl(2), and MMA liquid with various amounts of 3-methacryloxypropyltrimethoxysilane (MPS). The mixed paste was immersed in a simulated body fluid (Kokubo solution) that has a similar concentration in inorganic constituents to human blood plasma. After soaking for various periods, apatite formation on the cement was examined. Apatite formation was observed by the addition of CaCl(2) with contents of 16 mass % and more. Incorporation of MPS accelerates the apatite formation. Setting time of the cement was significantly elongated after the addition of MPS, whereas compressive strength significantly decreased with increasing the contents of CaCl(2) and MPS. The hardened cement containing 20 mass % of CaCl(2) in the powder and 20 mass % of MPS in the liquid showed a tendency to be more osteoconductive to living bone after implantation in rabbit tibiae than the unmodified cement. These results indicate that bioactivity of the modified PMMA bone cement increases with increasing amounts of MPS and CaCl(2). Bioactive bone cement is successfully obtained when it contains appropriate concentrations of alkoxysilane and calcium chloride.

Animals↗

[The pulsed water jet for selective removal of bone cement during revision arthroplasty].

Conventional tools used in prosthetic revision surgery have a limited range of action within the narrow cement mantle. Water jet cutting technology permits tiny and precisely controlled cuts, and may therefore be an alternative method of bone cement removal. Our study compares the cutting performance on bone cement (PMMA) and bone of a pulsed water jet and a continuous water jet. The aim of the study was to establish whether selective removal of PMMA is possible. 55 bone specimens (bovine femora) and 32 specimens of PMMA were cut with a continuous and a pulsed water jet at different pressures (40 MPa, 60 MPa) and pulse frequencies (0Hz, 50Hz, 250Hz). To ensure comparability of the results, the depths of cut were related to the hydraulic power of that part of the jet actually impinging on the material. While for PMMA the power-related depth of cut increased significantly with the pulse frequency, this did not apply to bone. The cuts produced in bone were sharp-edged. Since PMMA is more brittle than bone, the water jet caused cracks that enlarged further until particles of bone broke away. Although selective removal of PMMA without doing damage to the bone was not possible at the investigated settings of the jet parameters, the results do show that a pulsed water jet can cut bone cement much more effectively than bone. This is an important advantage over conventional non-selective tools for the removal of bone cement.

Animals↗

Complexity in modeling of residual stresses and strains during polymerization of bone cement: effects of conversion, constraint, heat transfer, and viscoelastic property changes.

Aseptic loosening of cemented joint prostheses remains a significant concern in orthopedic biomaterials. One possible contributor to cement loosening is the development of porosity, residual stresses, and local fracture of the cement that may arise from the in-situ polymerization of the cement. In-situ polymerization of acrylic bone cement is a complex set of interacting processes that involve polymerization reactions, heat generation and transfer, full or partial mechanical constraint, evolution of conversion- and temperature-dependent viscoelastic material properties, and thermal and conversion-driven changes in the density of the cement. Interactions between heat transfer and polymerization can lead to polymerization fronts moving through the material. Density changes during polymerization can, in the presence of mechanical constraint, lead to the development of locally high residual strain energy and residual stresses. This study models the interactions during bone cement polymerization and determines how residual stresses develop in cement and incorporates temperature and conversion-dependent viscoelastic behavior. The results show that the presence of polymerization fronts in bone cement result in locally high residual strain energies. A novel heredity integral approach is presented to track residual stresses incorporating conversion and temperature dependent material property changes. Finally, the relative contribution of thermal- and conversion-dependent strains to residual stresses is evaluated and it is found that the conversion-based strains are the major contributor to the overall behavior. This framework provides the basis for understanding the complex development of residual stresses and can be used as the basis for developing more complex models of cement behavior.

Bone Cements↗