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Antibiotic delivery system using bioactive bone cement consisting of Bis-GMA/TEGDMA resin and bioactive glass ceramics.

A novel drug delivery system containing cephalexin (CEX) as a model drug using a new bioactive bone cement consisting of 15% bisphenol-alpha-glycidyl methacrylate (Bis-GMA), 15% triethylene-glycol dimethacrylate (TEGDMA) resin and 70% apatite- and wollastonite-containing glass-ceramic (A-W GC) powder was investigated. A-W GC powder containing CEX powder hardened within 5 min after mixing with Bis-GMA/TEGDMA resin, and furthermore its compressive strength was expected to be higher than that of polymethylmethacrylate cement. In vitro CEX release from bioactive bone cement pellets in a simulated body fluid at pH 7.25 and 37 degrees C continued for more than 2 weeks. The drug release rate increased with increasing amount of CEX in the mixture. All of the drug release profiles followed the Higuchi equation at the initial stage, but not at later stages. As hydroxyapatite was precipitated out on the cement surface, the drug release rate decreased. These results suggest that the CEX release rate from bioactive bone cement could be controlled by varying the amount of drug in the cement system.

Biomechanical Phenomena↗

Effect of MMA-g-UHMWPE grafted fiber on mechanical properties of acrylic bone cement.

Ultrahigh molecular weight polyethylene (UHMWPE) fibers were treated with argon plasma for 5 min, followed by uv irradiation in methyl methacrylate (MMA)-chloroform solution for 5 h to obtain MMA-g-UHMWPE grafted fiber. The grafting content was estimated by the titration of esterification method. The grafting amount of 5280 nmol/g was the largest for the MMA concentration at 18.75 vol%. To improve the mechanical properties of acrylic bone cement, pure UHMWPE fiber and MMA-g-UHMWPE fiber were added to the surgical Simplex. P radiopaque bone cement. The mechanical properties including tensile strength, tensile modulus, compressive strength, bending strength, and bending stiffness were measured. Dynamic mechanical analysis was also performed. By comparing the effect of the pure UHMWPE fiber and MMA-g-UHMWPE grafted fiber on the mechanical properties of acrylic bone cement, it was found that the acrylic bone cement with MMA-g-UHMWPE grafted fiber had a more significant reinforcing effect than that with untreated UHMWPE fiber. This might be due to the improvement of the interfacial bonding between the grafted fibers and the acrylic bone cement matrix.

Acrylates↗

Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements.

In this in vitro study, the formation of a Staphylococcus aureus biofilm on six gentamicin-loaded bone cements (CMW1, CMW3, CMW Endurance, CMW2000, Palacos, and Palamed) was determined in a modified Robbins device over a 3 days time span and related with previously (Van de Belt et al., Biomaterials 21 (2000) 1981) measured kinetics of antibiotic release by these cement brands. The influence of gentamicin release on biofilm formation was quantified by expressing the number of colony-forming units on gentamicin-loaded cement relative to the number of viable organisms on unloaded cement of the same brand. Biofilms formed on all gentamicin-loaded cements, despite the release of antibiotics, followed a consistent pattern in time with a maximum number of colony-forming units per unit cement area found between 24 and 30 h after inoculation. None of the gentamicin-loaded cements showed a reduction in biofilm formation relative to unloaded cements within 6 h after inoculation, whereas only gentamicin-loaded CMW1 and Palacos reduced biofilm formation 24 h after inoculation. Alternatively, CMW Endurance, CMW2000, and Palamed did not exhibit any initial reductions in biofilm formation, but effects started after 72, 48, and 72 h, respectively. Biofilm reduction by gentamicin-loaded CMW3 lasted the longest from 24 to 72 h. Interestingly, each cement seemed to have a different "window-of-effectiveness" with regard to reduction in biofilm formation that did not relate with the gentamicin-release kinetics. Summarising, this study demonstrates that although gentamicin loading of bone cements yields reductions in biofilm formation, S. aureus is able to grow on gentamicin-loaded bone cements.

Biocompatible Materials↗

In vitro testing of ten bone cements after different time intervals from polymerization.

Biological response of cells to implanted bone cement is a fundamental but often neglected issue in successful cemented implants. In this study, ten acrylic bone cements for orthopedics were assayed using two different in vitro testing methods on L929 cells. The cements were mixed as prescribed, cured for either 1 h or 7 days and then extracted in minimum essential medium (MEM) according to the ISO standard for the preparation of samples. For the evaluation of cytotoxicity, the neutral red uptake assay (NRU) and the incorporation of propidium iodide (PI) were used to detect the viability/death of cells. The two methods were shown to be well correlated (p < 0.0001) in the case of both the 1-h and the 7-day extracts. Two cements, i.e. CERIM LT and CMW2, were found to be toxic after 1-h curing through both the spectrophotometric NRU assay and the cytofluorometric assay with PI. After 7-day curing, these two cements, as well as the Zimmer-low viscosity cement, were toxic according to the NRU assay. The toxic effect of all the cements disappeared after dilution of extracts 1:2 with MEM, except in the case of CERIM LT. In the search for the component inducing the toxic effect, the possible contribution of the residual monomer was discarded on the basis of literature data and the influence of various other factors was analyzed, including the contrast medium (barium sulphate or zirconium dioxide) and the concentrations of N,N-dimethyl-paratoluidine and of benzoyl peroxide (< 1% or > or = 1%). Unlike zirconium dioxide, barium sulphate was found to damage the cells at the 1-h endpoint. Benzoyl peroxide at concentration > or = 1% was found to affect cells at the same endpoint, whereas dimethylparatoluidine had no effect regardless of the proportion.

Animals↗

Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release.

In this study, the release of gentamicin as a function of time was measured for six different gentamicin-loaded bone cements and related with the surface roughness, porosity and wettability of the cements. Initial release rates varied little between the six bone cements (CMW1, CMW3, CMW Endurance, CMW 2000, Palacos, and Palamed) and ranged from 8.6 to 14.1 microg/cm2/h. The total amounts of gentamicin released after 1 week varied between 4.0 and 5.3% of the total amount of antibiotic incorporated for the CMW cements and was 8.4% for Palacos. Palamed released after 1 week significantly more of the gentamicin incorporated (17.0%). The wettability of all cements was similar (water contact angles between 70 and 80 degrees), but the surface roughness and the porosity of the cements varied markedly. Initial release rates increased with surface roughness, although the correlation coefficient was low (0.64), while total amounts released increased linearly (correlation coefficient 0.97) with the bulk porosity of the cements. Consequently, it can be concluded that the release kinetics of gentamicin from bone cements is controlled by a combination of surface roughness and porosity.

Bone Cements↗

An experimental technique for the investigation of three-dimensional stress in bone cement underlying a tibial plateau.

The technique of experimental model testing was applied to the analysis of stress at selected sites in bone cement underlying a tibial plateau. The investigation utilized a large model knee fabricated from materials which had mechanical properties similar to the actual tibial plateau and acrylic cement but which did not duplicate adequately the complexity of bone. A porous interface was created in the model between the materials representing the bone and cement. Three-dimensional strain rosettes were embedded into the cement and the model was loaded in a varus or valgus mode. Overloading resulted in breakdown of the modelled anterior and part of the posterior cement-bone interfaces, producing non-linear and in some cases erratic strains in the anterior section but repeatable linear results in the posterior section. The investigation highlighted the necessity for three-dimensional strain gauge investigations as opposed to two-dimensional studies. It is suggested that the approach could provide comparative information about different products and form the basis for a valuable design tool.

Bone Cements↗

Radiographic demarcation of the acetabular bone-cement interface. The effect of femoral head size.

Between 1983 and 1988, 182 total hip arthroplasties were inserted using modern cement techniques including metal-backed acetabular components. Femoral head size was 32 mm in 84, 22 mm in 98. Radiographic analysis revealed three-zone demarcation of acetabular bone-cement interface in 56% of the 32 mm group as compared to 5% of the 22 mm group at 19 and 24 months mean follow-up period, respectively. When a subgroup of women under 60 years of age was created to control variables, the high-grade demarcation rates were 67% and 18%, respectively. Although Charnley hip scores remain similar between the two groups, these results emphasize the adverse effects of large femoral head prostheses on cement-bone interface and underline the need for alternative methods of fixation.

Aged↗

[Allergic reaction to components of bone cement after total knee arthroplasty].

There are many reports about allergic reactions in association with total hip or knee arthroplasty. While most studies focus on allergic reactions to metallic components, only few reports exist about reactions to bone cement or its ingredients. We report about a patient who developed eczema at the knee and the lower leg one year after cemented TKR. Patch testing showed as potential causes contact allergic reactions to nickel and benzoylperoxide, an ingredient of the here used bone cement. The local and temporal association between onset of eczema and knee arthroplasty suggests a causal link. Benzoylperoxide as potential contact allergen in bone cement is so far almost neglected. The development of extended testing procedures and data collection should provide further information and better care of these patients. The development of special bone cements for patients with allergic diathesis is requested.

Arthroplasty, Replacement, Knee↗

Complications associated with bone cementing for the treatment of giant cell tumors of bone.

Aretrospective review was conducted of giant cell tumors treated between 1984 and 1998 using the technique of aggressive curettage through a large bone window followed by acrylic cement reconstruction. Fifteen patients with a mean follow-up time of 46 months (range, 24-188 months) were identified. One patient had a local recurrence 24 months postoperatively. All the patients showed a radiolucent zone at the bone-cement interface up to 2.5 mm in width during the first 6 months after operation. However, the radiolucent zones were nonprogressive and did not affect the stability of the bone cement. Osteoarthritis of the knee joint occurred 14 years postoperatively in one patient with an intraarticular fracture at presentation. A stress fracture occurred in one patient who had the largest tumor in the distal femur. Acrylic cement reconstruction is a safe and effective procedure that provides local adjuvant therapy. Giant cell tumors with an associated intraarticular fracture remain a challenging problem to treat.

Adolescent↗

[Ultrasonic modelling of bone cement - (reoperation of total hip endoprosthesis) (author's transl)].

In medicine ultrasound is very common in diagnostic and therapeutic applications, in surgery especially as so-called ultrasonic lithotripsy. Up to now experiences in bone surgery are not very successful. Bone cement (PMMA) is a thermoplastic material. Therefore results of ultrasonic lithotripsy cannot be simply transmitted. Investigations show that, because of their thermoplastic quality, the ultrasonic method may be helpful in modelling bone cement, for example in changing endoprosthesis. The preconditions for the use of high frequent oscillating probes are examined experimentally. The necessary visual distinction of bone cement and natural bone may be intensified by fluorochrome labelling of cement.

Bone Cements↗

Stress relaxation modelling of polymethylmethacrylate bone cement.

This paper describes tests that were carried out to model the stress relaxation behaviour of polymethylmethacrylate (PMMA) bone cement. Stress relaxation of bone cement is believed to be a significant factor in the mechanism of load transfer in the femoral stem of a polished, collarless taper-fit replacement hip joints. It is therefore important that this condition and its implications are understood. Stress relaxation was carried out on PMMA samples of varying age in four-point bending configuration. It was shown that the samples stiffened with age and that the amount of stress relaxation reduced as the samples aged. The experimental results of the stress relaxation were accurately modelled on the double exponential of the Maxwell model so that long-term predictions of the stress condition could be made from short-term mechanical tests.

Bone Cements↗

Renal dysfunction after total knee replacement is not aggravated by bone cement.

BACKGROUND: Total knee replacement (TKR) has been associated with postoperative renal dysfunction. The use of monomeric methylmethacrylate (MMA) bone cement causes hypotension by several mechanisms. METHODS: In 30 patients undergoing TKR with (n = 16), or without (n = 14) bone cement, serum levels of creatinine, cystatin C and creatine kinase (CK) and urinary levels of creatinine and markers for glomerular (albumin, IgG) and tubular (protein HC) function were recorded preoperatively and on days 1, 2, 4 and 8 postoperatively. RESULTS: There were no changes in serum creatinine. Both groups had a transient, 5-fold rise in CK and a continuous increase in cystatin C. The urinary concentration of proteins increased postoperatively with a peak in the glomerular markers on day 1 and in the tubular marker on day 2. There were no significant differences in proteinuria between the groups. The 95% CIs for the difference in the means of the AUCs of the logarithmically transformed values for the proteins were never more than 19%. On day 8 all proteins had returned to their preoperative levels. CONCLUSION: Postoperatively, there was a transient increased leakage of proteins, indicating glomerular and tubular dysfunction. This was not influenced by the use of MMA bone cement.

Aged↗

Improvement of fatigue properties of poly(methyl methacrylate) bone cement by means of plasma surface treatment of fillers.

The fatigue properties of poly(methyl methacrylate) (PMMA) bone cement were significantly improved through 13.56-MHz radio frequency plasma treatments on the X-ray opaque powder and on the reinforcing fibers. For the plasma treatments of particle surfaces, a specially designed plasma reactor was used to modify the surfaces of the ZrO2 powder (X-ray opaque filler) and milled carbon fibers (reinforcing filler). The reactor chamber was designed to be rotated continuously to mix the particles during the plasma treatments to obtain uniformly treated particle surfaces. The surface peroxides resulting from the plasma treatments seemed to have a significant effect on the improvement of fatigue properties. The peroxides on the particles may yield free radicals by the reaction with the reducing agent (N,N-dimethyl-p-toluidine) in the bone cement mixture, which can initiate methyl methacrylate (MMA) polymerization. Through this graft polymerization process, the interfacial bond strength between the filler particles and the MMA matrix may be enhanced, resulting in efficient stress transfer from the matrix to the fillers. The best results of the fatigue tests were seen in the reinforced bone cement, which contained surface modified fillers, with hexamethyldisiloxane plasma, and with O2 plasma posttreatment.

Biocompatible Materials↗

Rheology of acrylic bone cements.

The rheological properties of setting acrylic bone cements were examined with a rotational cone and plate viscometer. The cements were tested over two orders of magnitude of shear rate to determine the nature of any non-Newtonian flow behavior. All three cements behaved with moderate pseudoplasticity (i.e., shear thinning) during setting, suggesting the use of higher pressures during administration for better flow and penetration. The low viscosity brand was found to be nearly one-half as viscous as the conventional cements during the working time (i.e., 2-5 minutes). A series of sieving experiments were performed to determine the particle size distributions of the powder components. Statistical analysis (chi square) showed the cements to have different distributions, with the low viscosity brand containing a larger proportion of smaller polymer particles. This difference is thought to contribute to the lower viscosity of this cement.

Bone Cements↗

The relationship between porosity and fatigue characteristics of bone cements.

In this study, the fatigue strengths of acrylic cement prepared by various commercially available reduced pressure mixing systems were compared with the fatigue strength of cement mixed by hand (control) under atmospheric conditions. The following observations were made from this investigation. The mean fatigue strength of reduced pressure mixed acrylic bone cement is double that of cement mixed by hand using an open bowl, 11,354+/-6,441 cycles to failure for reduced pressure mixing in comparison with 5,938+/-3,199 cycles for mixing under atmospheric conditions. However, the variability in mean fatigue strengths of reduced pressure mixed bone cement is greater for some mixing devices. The variation in fatigue strengths for the different mixing techniques is explained by the different porosity distributions. The design of the reduced pressure mixing system and the technique employed during mixing strongly contribute to the porosity distribution within the acrylic bone cement. The level of reduced pressure applied during cement mixing has an effect on the fatigue strength of bone cement, but the mixing mechanism is significantly more influential.

Biocompatible Materials↗

Effect of an ultrasonic device on temperatures generated in bone and on bone-cement structure.

Cement removal during revision arthroplasty can be a tedious, time-consuming process. The usual methods of removing cement include high-speed drills, chisels, saws and reamers, which are often associated with fracture and/or perforation of the femoral shaft. Ultrasound has been used in dentistry to remove plaque and in ophthalmology to remove cataracts and is now applied to cement removal in orthopaedic surgery. There is little data available on the effect of ultrasound on temperatures generated in bone and on its effects on the structure of bone-cement. A cement mantle was constructed in the intramedullary canal in each of six 10 cm lengths of human cadaver femora. A temperature probe was then inserted into predrilled holes and temperatures generated by the ultrasonic device were recorded under a variety of conditions. In addition, a cement cylinder was microscopically evaluated after an ultrasonic tool had been inserted. Temperatures generated by the ultrasonic tool in cadaver bone were no higher than previously reported temperatures of 140 degrees C generated by high-speed drills. Furthermore, temperatures at the bone-cement interface never exceeded 60 degrees C when saline irrigation was used in conjunction with the ultrasonic tools, and were below 40 degrees C 1 minute after deactivation of the device. Microscopic examination shows that ultrasound produced local changes in the structure of bone-cement converting it from a microscopically spherical interlocked material to one that appears homogeneous and granular.

Bone Cements↗

Bioactive bone cement: effects of phosphoric ester monomer on mechanical properties and osteoconductivity.

A new bioactive bone cement, designated GBC, has been developed. It consists of polymethyl methacrylate (PMMA) as an organic matrix and bioactive glass beads as an inorganic filler. The bioactive beads, consisting of MgO--CaO--SiO(2)--P(2)O(5)--CaF(2) glass, have been newly designed, and a novel PMMA powder was selected. The purpose of the present study was to evaluate the effects on mechanical properties and osteoconductivity of adding a phosphoric ester (PE) monomer to the cement as an adhesion-promoting agent. Four kinds of cements were prepared: GBC, GBC with PE (designated GBC/PE), a cement consisting of the same PMMA used in GBC with apatite- and wollastonite-containing glass-ceramic (AW-GC) powder (designated AWC), and AWC with PE (designated AWC/PE). Each filler was added to the cement at 70 wt %. Adding PE to either GBC or AWC resulted in increases in the bending strength and decreases in the Young's modulus compared with the unmodified cements. Cements were packed into the intramedullar canals of rat tibiae to evaluate osteoconductivity as determined by an affinity index. Rats were sacrificed at 4 and 8 weeks after operation. The affinity index (length of bone in direct contact with the cement expressed as a percentage of the total length of the cement surface) was calculated for each cement. Adding PE to either GBC or AWC resulted in significant increases in the affinity index compared with the unmodified cements. The affinity index for GBC was significantly higher than that of AWC, and that for GBC/PE was also significantly higher than that of AWC/PE. The affinity indices for each cement increased significantly with time up to 8 weeks. Our study revealed that the higher osteoconductivity of GBC/PE was due to the large alkyl group in the PE monomer, to the hydrophilicity of the phosphoric acid in the PE monomer, and to the higher bioactivity of the bioactive glass beads at the cement surface. GBC/PE shows promise as an alternative bone cement with improved properties compared with conventional PMMA bone cement.

Animals↗

Bone cements as adjuvant techniques for ossicular chain reconstruction.

HYPOTHESIS: The osseointegrative capacity of medical-grade bone cement can be used to improve fixation and prevent displacement of an ossicular prosthesis in a guinea pig model. BACKGROUND: Successful ossiculoplasty requires a firm connection between the vibrating tympanic membrane and the inner ear. In patients requiring revision ossiculoplasty, half of failures are due to prosthesis displacement. Bone cements have been used as prosthetic material in craniofacial surgery, and their adhesive and osseointegrative properties make them ideal for use in ossicular reconstruction. METHODS: Twenty-four adult male guinea pigs underwent a postauricular surgical approach for access to the middle ear. Hydroxyapatite and Dahllite cements were used in an alternating fashion to fix ossicular bone. Four animals were killed immediately to demonstrate mechanical bonding of the ossicles at the time of application. Nineteen animals were killed 8 weeks postoperatively to assess bonding capacity and histologic inflammation. RESULTS: Both cements mechanically bonded the ossicles at the time of application, but Dahllite cement set faster in the moist environment of the middle ear space. Histologic examination showed bonding of the ossicles with both cements, with little evidence of inflammation or foreign body reaction. CONCLUSIONS: Hydroxyapatite and Dahllite bone cements showed evidence of osseointegration with ossicular bone in the guinea pig model. Further studies are under way to determine the osseointegrative capacity of Dahllite cement between the guinea pig malleus and a partial prosthesis, and any ototoxic effects with use in the middle ear.

Animals↗