Two-solution Cement Research Articles

A novel chlorhexidine-releasing composite bone cement: Characterization of antimicrobial effectiveness and cement strength

The addition of calcium phosphate fillers or antimicrobials to bone cements seems to produce inferior materials. In this study, a two-solution bone cement composite was designed for high viscosity and high pseudoplasticity to improve injection and mitigate the risk of extravasation. By pre-mixing these cements, the fillers are incorporated into the matrix and should not detrimentally affect the performance properties. To expand the functionality of this cement system, the addition of bioactive and antimicrobial phases were explored. Brushite and chlorhexidine were used as calcium phosphate filler and the antimicrobial phase, respectively. By controlling the free radical quenching mechanism provided by the chlorhexidine molecule, it was possible to achieve high polymer conversion rates. This phenomenon led to cement strength retention while successfully preventing microbial proliferation in an environment exposed to the cement surface. Based on these results, two-solution cement composite prepared with high concentrations of brushite and chlorhexidine diacetate salt hydrate may provide an attractive bioactive and antimicrobial cement for load-bearing applications.

Preparation and Characterization of Injectable Brushite Filled-Poly (Methyl Methacrylate) Bone Cement.

Powder-liquid poly (methyl methacrylate) (PMMA) bone cements are widely utilized for augmentation of bone fractures and fixation of orthopedic implants. These cements typically have an abundance of beneficial qualities, however their lack of bioactivity allows for continued development. To enhance osseointegration and bioactivity, calcium phosphate cements prepared with hydroxyapatite, brushite or tricalcium phosphates have been introduced with rather unsuccessful results due to increased cement viscosity, poor handling and reduced mechanical performance. This has limited the use of such cements in applications requiring delivery through small cannulas and in load bearing. The goal of this study is to design an alternative cement system that can better accommodate calcium-phosphate additives while preserving cement rheological properties and performance. In the present work, a number of brushite-filled two-solution bone cements were prepared and characterized by studying their complex viscosity-versus-test frequency, extrusion stress, clumping tendency during injection through a syringe, extent of fill of a machined void in cortical bone analog specimens, and compressive strength. The addition of brushite into the two-solution cement formulations investigated did not affect the pseudoplastic behavior and handling properties of the materials as demonstrated by rheological experiments. Extrusion stress was observed to vary with brushite concentration with values lower or in the range of control PMMA-based cements. The materials were observed to completely fill pre-formed voids in bone analog specimens. Cement compressive strength was observed to decrease with increasing concentration of fillers; however, the materials exhibited high enough strength for consideration in load bearing applications. The results indicated that partially substituting the PMMA phase of the two-solution cement with brushite at a 40% by mass concentration provided the best combination of the properties investigated. This alternative material may find applications in systems requiring highly injectable and viscous cements such as in the treatment of spinal fractures and bone defects.

Characterization of a new composite PMMA-HA/Brushite bone cement for spinal augmentation.

Calcium phosphate fillers have been shown to increase cement osteoconductivity, but have caused drawbacks in cement properties. Hydroxyapatite and Brushite were introduced in an acrylic two-solution cement at varying concentrations. Novel composite bone cements were developed and characterized using rheology, injectability, and mechanical tests. It was hypothesized that the ample swelling time allowed by the premixed two-solution cement would enable thorough dispersion of the additives in the solutions, resulting in no detrimental effects after polymerization. The addition of Hydroxyapatite and Brushite both caused an increase in cement viscosity; however, these cements exhibited high shear-thinning, which facilitated injection. In gel point studies, the composite cements showed no detectable change in gel point time compared to an all-acrylic control cement. Hydroxyapatite and Brushite composite cements were observed to have high mechanical strengths even at high loads of calcium phosphate fillers. These cements showed an average compressive strength of 85 MPa and flexural strength of 65 MPa. A calcium phosphate-containing cement exhibiting a combination of high viscosity, pseudoplasticity and high mechanical strength can provide the essential bioactivity factor for osseointegration without sacrificing load-bearing capability.

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

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

Two‐solution bone cements with cross‐linked micro and nano‐particles for vertebral fracture applications: Effects of zirconium dioxide content on the material and setting properties

The application of bone cements for the treatment of vertebral compression fracture requires radiopaque materials for adequate visualization of the flow under fluoroscopy. Besides high radiopacity, it is desirable for the cement to have relatively low viscosity, high compressive strength and appropriate curing parameters. In this study, the properties of novel two-solution bone cements composed of cross-linked poly (methyl methacrylate) PMMA microspheres or nanospheres added to the linear polymer phase were assessed for formulations with increasing concentrations of zirconium dioxide (ZrO(2)). The addition of a cross-linked phase in the standard two-solution formulation (TSBC) was observed to improve the material properties by increasing setting time and decreasing maximum polymerization temperatures and decreasing the initial viscosity in comparison to the standard cement. The properties of three formulations (TSBC, modified two-solution containing cross-linked PMMA microspheres, and nanospheres) were measured for cements prepared at 0%, 5%, 20%, and 30% ZrO(2) and compared to KyphX. Cements prepared with cross-linked particles exhibited significantly higher compressive strength than the standard-two solution cement and KyphX at increasing radiopacifier concentrations. Furthermore, cement viscosity was increased by the addition of increasing concentrations of ZrO(2) in the modified two-solution cements, whereas the maximum polymerization exotherm and setting time of these materials were decreased. This study indicates that the addition of high concentrations of ZrO(2) significantly affects the properties of two-solution cements acting as a reinforcing phase when cross-linked spheres are added. These materials were observed to be suitable for vertebroplasty applications.

Analysis of the shelf life of a two-solution bone cement

Two-solution bone cement consists of methyl methacrylate monomer and poly(methyl methacrylate) polymer dissolved together to yield a viscous solution. Two solutions are used such that the initiator, benzoyl peroxide (BPO), is placed in one solution and the activator, N, N, dimethyl- para-toluidine, is placed in the other. This approach to bone cement provides for a simplified use during surgery and eliminates some of the sources of porosity formation. However, the BPO-containing solution cement will spontaneously polymerize over time and will limit the useful shelf life of this component of the system. The activator-containing component is much more stable and is not as susceptible to spontaneous polymerization. In making two-solution cements, it is envisioned that antibiotics may be incorporated and that the polymer may be sterilized using γ(gamma)-irradiation. Therefore, this study investigated the shelf life of the initiator-containing solution bone cement and studied the effects of initiator concentration, γ-irradiation, gentamicin addition, and the role of storage temperature. Isothermal differential scanning calorimetry (Iso-DSC) techniques were used to monitor the polymerization of BPO-containing solutions. It was found that the shelf life was highly temperature dependent and followed an Arrhenius expression where refrigeration storage (4 °C) yielded approximately a 12-month storage time, while 70 °C storage results in setting in about 5–7 min. γ-irradiation and gentamicin addition did not significantly affect the shelf life. Initiator concentration affected storage time with higher levels resulting in shorter shelf life.

Gentamicin release from two-solution and powder-liquid poly(methyl methacrylate)-based bone cements by using novel pH method.

The release of gentamicin as a function of time was measured for Palacos and two-solution bone cements by using a novel pH technique. The pH of an aqueous solution of gentamicin is a function of the gentamicin concentration and it decreases linearly over concentrations of 0.0-0.1 wt %. Therefore, a new, direct, and inexpensive in vitro technique was developed based on continuous readings of the pH in phosphate-buffered saline (PBS) at 37 degrees C to determine the release kinetics of gentamicin from poly(methyl methacrylate) (PMMA)-based bone cement. In addition, this method was used to compare the release profiles of Palacos R-40 bone cement with a two-solution bone cement developed in our laboratory and loaded with two different concentrations of gentamicin sulfate. Finally, the pH-based method was used to track the elution of gentamicin in both mixed and static conditions to determine the effect of mixing on the diffusion of gentamicin out of the cement. It was found that Palacos R-40 released 4.95 +/- 0.22 wt % of its gentamicin after 24 h in PBS solution. This data compares favorably with previously reported values of gentamicin elution from Palacos R-40, which ranged from 3 to 8 wt % of the total amount of incorporated gentamicin, depending on the size and the surface area of the samples. The results show that Palacos samples released 4.84 +/- 0.27 mg after 24 h, a two-solution cement loaded with an equivalent concentration of gentamicin sulfate released 3.81 +/- 0.52 mg, and two-solution cement loaded with twice the concentration of Palacos released 5.53 +/- 0.26 mg of gentamicin. A higher percentage of release was recorded from Palacos than from the two-solution bone cement, and the effect of PBS mixing conditions on the release kinetics was only significant in the early stages of release and not at 24 h. It was concluded that monitoring the pH is an effective technique to measure gentamicin release from PMMA-based bone cements in PBS solution.

Effect of initiation chemistry on the fracture toughness, fatigue strength, and residual monomer content of a novel high-viscosity, two-solution acrylic bone cement.

Porous-free, two-solution bone cements have been developed in our laboratory as an alternative to commercial powder/liquid formulations. Each pair of solutions consist of poly(methyl methacrylate) (PMMA) powder dissolved in methyl methacrylate (MMA) monomer, with benzoyl peroxide (BPO) added to one solution as the initiator and N,N-dimethyl-p-toluidine (DMPT) added to the other as the activator. When mixed, the solutions polymerize via a free radical reaction, which is governed by the concentrations of initiator and activator and their molar stoichiometry. Previous work by the authors has demonstrated that these two-solution cement compositions are comparable to Simplex P bone cement in polymerization exotherm, setting time, and flexural mechanical properties. This study was designed to evaluate the effect of BPO and DMPT concentrations, along with their molar ratio, on the fracture toughness, fatigue strength, and residual monomer content of the experimental compositions. The results showed that fracture toughness and fatigue strength for the solution cements were comparable to Simplex P and were not significantly affected by the BPO concentration or the BPO:DMPT molar ratio; however, the highest DMPT concentration yielded significantly lower values for both variables. Residual monomer content was significantly affected by both the individual concentrations of BPO and DMPT and their molar ratios. The two-solution cements had significantly higher residual monomer contents versus Simplex P; however, this can be attributed to their higher initial monomer concentration rather than a lower degree of conversion.