Spray drying: Inhalable powders for pulmonary gene therapy.

Gene therapy holds potential in the treatment of many lung pathologies, as indicated by the growing number of clinical trials in recent decades. Pulmonary delivery of gene therapies via inhalation enables localised treatment while the extensive lung surface area promotes enhanced drug absorption. However, loss of nucleic acid integrity during the aerosolisation process, pulmonary clearance, and undesirable drug deposition, pose a major challenge for local delivery. Therefore, the development of nucleic acids into a stable inhalable pharmaceutical preparation would be advantageous. Dry powder inhalers (DPIs) are considered superior compared to nebulisation and pressurised-metered dose inhalers (pMDIs) due to the production of a stable dry formulation, an easy dispensing process, and minimal physical stress. DPIs are commonly produced via spray drying with a range of excipients, solvents, and separation options which can be modified to improve the stability of the nucleic acid cargo. This review details the ideal characteristics for pulmonary delivery and formulation of DPIs for gene therapy to the lungs. The utilisation of spray drying for the production of nucleic acid-containing DPIs is evaluated, with a specific focus on the influence of instrument parameters, the nucleic acid delivery system, and excipients with respect to cargo stability and functionality.

Graphene Oxide and Graphene Reinforced PMMA Bone Cements: Evaluation of Thermal Properties and Biocompatibility.

The incorporation of well-dispersed graphene oxide (GO) and graphene (G) has been demonstrated as a promising solution to improve the mechanical performance of polymethyl methacrylate (PMMA) bone cements in an attempt to enhance the long-term survival of the cemented orthopaedic implants. However, to move forward with the clinical application of graphene-based PMMA bone cements, it is necessary to ensure the incorporation of graphene-based powders do not negatively affect other fundamental properties (e.g., thermal properties and biocompatibility), which may compromise the clinical success of the implant. In this study, the effect of incorporating GO and G on thermal properties, biocompatibility, and antimicrobial activity of PMMA bone cement was investigated. Differential scanning calorimetry studies demonstrated that the extent of the polymerisation reaction, heat generation, thermal conductivity, or glass transition temperature were not significantly (p > 0.05) affected by the addition of the GO or G powders. The cell viability showed no significant difference (p > 0.05) in viability when MC3-T3 cells were exposed to the surface of G- or GO-PMMA bone cements in comparison to the control. In conclusion, this study demonstrated the incorporation of GO or G powder did not significantly influence the thermal properties or biocompatibility of PMMA bone cements, potentially allowing its clinical progression.

Graphene and graphene oxide functionalisation with silanes for advanced dispersion and reinforcement of PMMA-based bone cements.

The reinforcement of PMMA bone cements using carbon based nanomaterials has demonstrated to be a potential solution to their poor mechanical properties. The achievement of an optimal dispersion of the nanoparticles within the polymeric matrix is a crucial but not easy stage in the production of high-quality reinforced materials. In this work, a useful route for the graphene (G) functionalisation, via silanisation with (3-methacryloxypropyl) trimethoxy silane (MPS), has been developed, providing a remarkable enhancement in dispersibility and mechanical properties. With the purpose to define the critical graphene surface oxidation parameters for an optimal silanisation, different routes were thoroughly analysed using infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The results showed that the silanisation significantly improved the G dispersibility: whereas the pristine G dispersion fell down within the first 24 h, the silanised G showed an adequate stability after 5 days. Additionally, this improved dispersibility produced a notable increase in the mechanical properties of the G-reinforced bone cements: in comparison with the pristine G, the compression and bending strength of silanised G increased by 12% and by 13.7% respectively and the fracture toughness by 28%. These results provide very useful information on the relevance that the characteristics of the superficial oxidation of graphene have on the effectiveness of the silanisation process, besides an interesting functionalisation procedure for advanced dispersion and reinforcement of G-PMMA bone cements.

Characterisation and constitutive modelling of biaxially stretched poly(L-lactic acid) sheet for application in coronary stents.

A poly(L-lactic acid) stent is exposed to a variety of processing techniques, temperatures and environmental conditions during its lifecycle, from the manufacturing process, to crimping through to deployment within the body. The effect of the biaxial stretching procedure and the effects of temperature and extension rate (post-processing) on the mechanical response of poly(L-lactic acid) are hereby investigated, and a constitutive model calibrated against experimental data is proposed. Dumb-bell specimens were punched from biaxially stretched sheets subjected to different processing histories, and tested under uniaxial tension at various temperatures (20, 37 and 55 °C) and extension rates (1, 5 and 10 mm/min). A Design of Experiments methodology was employed to identify the parameters that had the most significant effect on the mechanical response of the polymer. Results show that the elastic modulus and yield strength of the stretched sheets are strongly dependent on the aspect ratio of the biaxial deformation, along with the temperature during uniaxial deformation (post-processing). In contrast, these mechanical properties were not heavily dependent on extension rate (post-processing). A transversely isotropic, elastic-plastic constitutive model for finite element implementation is proposed, with the intention that it may be used as a design tool for developing high stiffness, thin-strut polymeric stents that contend with the performance of their metallic counterparts.

Pore-forming bioinks to enable spatio-temporally defined gene delivery in bioprinted tissues.

The regeneration of complex tissues and organs remains a major clinical challenge. With a view towards bioprinting such tissues, we developed a new class of pore-forming bioink to spatially and temporally control the presentation of therapeutic genes within bioprinted tissues. By blending sacrificial and stable hydrogels, we were able to produce bioinks whose porosity increased with time following printing. When combined with amphipathic peptide-based plasmid DNA delivery, these bioinks supported enhanced non-viral gene transfer to stem cells in vitro. By modulating the porosity of these bioinks, it was possible to direct either rapid and transient (pore-forming bioinks), or slower and more sustained (solid bioinks) transfection of host or transplanted cells in vivo. To demonstrate the utility of these bioinks for the bioprinting of spatially complex tissues, they were next used to zonally position stem cells and plasmids encoding for either osteogenic (BMP2) or chondrogenic (combination of TGF-ß3, BMP2 and SOX9) genes within networks of 3D printed thermoplastic fibers to produce mechanically reinforced, gene activated constructs. In vivo, these bioprinted tissues supported the development of a vascularised, bony tissue overlaid by a layer of stable cartilage. When combined with multiple-tool biofabrication strategies, these gene activated bioinks can enable the bioprinting of a wide range of spatially complex tissues.

Processing-property relationships of biaxially stretched poly(L-lactic acid) sheet for application in coronary stents.

The development of coronary stents from poly(L-lactic acid) requires knowledge of its mechanical properties and the effects of manufacturing processes on those properties. The effects of the biaxial stretching procedure on the mechanical and microstructural properties of poly(L-lactic acid) are hereby investigated. The mechanical properties were evaluated before and after biaxial stretching, with a Design of Experiments methodology employed to identify processing parameters that had the most significant effect on the elastic modulus and yield strength of the biaxially stretched sheets. Microstructural characterisation was performed using differential scanning calorimetry to evaluate crystallinity and thermal transitions of the biaxially stretched sheets. The results show that the mechanical properties of the stretched sheets are highly dependent on the extent of stretch ratio applied during processing; however, neither the elastic modulus nor yield strength are directly attributable to crystallinity, but are affected by the degree of amorphous orientation. The results of this study have the potential to be applied in the design of high stiffness, thin-strut polymeric expandable scaffolds for the application of coronary stents.

Effect of combined flexion and external rotation on measurements of the proximal femur from anteroposterior pelvic radiographs.

INTRODUCTION: Fixed flexion and external rotation contractures are common in patients with hip osteoarthritis and, in particular, before total hip replacement (THR). We aimed to answer the following question: how does combined flexion and external rotation of the femur influence the radiographic assessment of (1) femoral offset (FO) (2) neck-shaft angle (NSA) and (3) distance (parallel to the femoral axis) from greater trochanter to femoral head center (GT-FHC)? HYPOTHESIS: Combined flexion and external rotation impact the accuracy of two-dimensional (2D) proximal femur measurements. MATERIALS AND METHODS: Three-dimensional (3D) CT segmentations of the right femur from 30 male and 42 female subjects were acquired and used to build a statistical shape model. A cohort (n=100; M:F=50:50) of shapes was generated using the model. Each 3D femur was subjected to external rotation (0°-50°) followed by flexion (0°-50°) in 10° increments. Simulated radiographs of each femur in these orientations were produced. Measurements of FO, NSA and GT-FHC were automatically taken on the 2D images. RESULTS: Combined rotations influenced the measurement of FO (p<0.05), NSA (p<0.001), and GT-FHC (p<0.001). Femoral offset was affected predominantly by external rotation (19.8±2.6mm [12.2 to 26.1mm] underestimated at 50°); added flexion in combined rotations only slightly impacted measurement error (20.7±3.1mm [13.2 to 28.8mm] underestimated at 50° combined). Neck-shaft angle was reduced with flexion when external rotation was low (9.5±2.1° [4.4 to 14.2°] underestimated at 0° external and 50° flexion) and increased with flexion when external rotation was high (24.4±3.9° [15.7 to 31.9°] overestimated at 50° external and 50° flexion). Femoral head center was above GT by 17.0±3.4mm [3.9 to 22.1mm] at 50° external and 50° flexion. In contrast, in neutral rotation, FHC was 12.2±3.4mm [3.9 to 22.1mm] below GT. DISCUSSION: This investigation adds to current understanding of the effect of femoral orientation on preoperative planning measurements through the study of combined rotations (as opposed to single-axis). Planning measurements are shown to be significantly affected by flexion, external rotation, and their interaction. LEVEL OF EVIDENCE: IV Biomechanical study.

Mesenchymal stem cell fate following non-viral gene transfection strongly depends on the choice of delivery vector.

Controlling the phenotype of mesenchymal stem cells (MSCs) through the delivery of regulatory genes is a promising strategy in tissue engineering (TE). Essential to effective gene delivery is the choice of gene carrier. Non-viral delivery vectors have been extensively used in TE, however their intrinsic effects on MSC differentiation remain poorly understood. The objective of this study was to investigate the influence of three different classes of non-viral gene delivery vectors: (1) cationic polymers (polyethylenimine, PEI), (2) inorganic nanoparticles (nanohydroxyapatite, nHA) and (3) amphipathic peptides (RALA peptide) on modulating stem cell fate after reporter and therapeutic gene delivery. Despite facilitating similar reporter gene transfection efficiencies, these nanoparticle-based vectors had dramatically different effects on MSC viability, cytoskeletal morphology and differentiation. After reporter gene delivery (pGFP or pLUC), the nHA and RALA vectors supported an elongated MSC morphology, actin stress fibre formation and the development of mature focal adhesions, while cells appeared rounded and less tense following PEI transfection. These changes in MSC morphology correlated with enhanced osteogenesis following nHA and RALA transfection and adipogenesis following PEI transfection. When therapeutic genes encoding for transforming growth factor beta 3 (TGF-ß3) and/or bone morphogenic protein 2 (BMP2) were delivered to MSCs, nHA promoted osteogenesis in 2D culture and the development of an endochondral phenotype in 3D culture, while RALA was less osteogenic and appeared to promote a more stable hyaline cartilage-like phenotype. In contrast, PEI failed to induce robust osteogenesis or chondrogenesis of MSCs, despite effective therapeutic protein production. Taken together, these results demonstrate that the differentiation of MSCs through the application of non-viral gene delivery strategies depends not only on the gene delivered, but also on the gene carrier itself. STATEMENT OF SIGNIFICANCE: Nanoparticle-based non-viral gene delivery vectors have been extensively used in regenerative medicine, however their intrinsic effects on mesenchymal stem cell (MSC) differentiation remain poorly understood. This paper demonstrates that different classes of commonly used non-viral vectors are not inert and they have a strong effect on cell morphology, stress fiber formation and gene transcription in MSCs, which in turn modulates their capacity to differentiate towards osteogenic, adipogenic and chondrogenic lineages. These results also point to the need for careful and tissue-specific selection of nanoparticle-based delivery vectors to prevent undesired phenotypic changes and off-target effects when delivering therapeutic genes to damaged or diseased tissues.

Optimisation of the mechanical and handling properties of an injectable calcium phosphate cement.

Calcium phosphate cements have the potential to be successful in minimally invasive surgical techniques, like that of vertebroplasty, due to their ability to be injected into a specific bone cavity. These bone cements set to produce a material similar to that of the natural mineral component in bone. Due to the ceramic nature of these materials they are highly brittle and it has been found that they are difficult to inject. This study was carried out to determine the factors that have the greatest effect on the mechanical and handling properties of an apatitic calcium phosphate cement with the use of a Design of Experiments (DoE) approach. The properties of the cement were predominantly influenced by the liquid:powder ratio and weight percent of di-sodium hydrogen phosphate within the liquid phase. An optimum cement composition was hypothesised and tested. The mechanical properties of the optimised cement were within the clinical range for vertebroplasty, however, the handling properties still require improvement.

Effect of curing characteristics on residual stress generation in polymethyl methacrylate bone cements.

Residual stresses resulting from the shrinkage of polymethyl methacrylate (PMMA) bone cement have been implicated in the formation of cracks in cement mantles following total hip arthroplasty. This study investigates whether two such cements, with differentiated solidification characteristics (i.e. working and setting times), display significant differences in their residual stress characteristics in an experiment designed to replicate the physical conditions of total hip arthroplasty. Experiments were performed using a representative femoral construct to measure and compare the temperatures and residual strains developed for standard PMMA cement mantles (CMW 1 Gentamicin) and slow curing cement mantles (SmartSet HV Gentamicin) during and following polymerization. These experimental results revealed no statistically significant difference (t-test, p > 0.05) for peak exotherm temperature and residual strain levels between the cements (measured after 3 h). The tailored polymerization characteristics of the slow-curing cement do not significantly affect residual stress generation, compared with the standard cement. It is often considered that residual stresses significantly relax following polymerization and before biomechanical loads are first applied during rehabilitation (up to 3 days later). This was examined for durations of 18 h to 3 days. Axial strains in the model femur and stem reduced by averages of 5.5 and 7.9 per cent respectively, while hoop strains in the stem exhibited larger reductions. An axisymmetric transient thermoelastic finite element model of the experiment was developed, allowing residual stresses to be predicted based on differential scanning calorimetry (DSC) measurements of the heat released throughout the exothermic curing reaction. The model predictions closely replicated the experimental measurements of both temperature and residual strain at 3 h, suggesting that residual strains can be fully accounted for by the thermal contraction mechanism associated with cooling after solidification.

Incorporation of large amounts of gentamicin sulphate into acrylic bone cement: effect on handling and mechanical properties, antibiotic release, and biofilm formation.

Bacterial infection remains a significant complication following total joint replacement. If infection is suspected when revision surgery is being performed, a large dose of antibiotic, usually gentamicin sulphate, is often blended with the acrylic bone cement powder in an attempt to reduce the risk of recurrent infection. In this in-vitro study the effect of small and large doses of gentamicin sulphate on the handling and mechanical properties of the cement, gentamicin release from the cement, and in-vitro biofilm formation by clinical Staphylococcus spp. isolates on the cement was determined. An increase in gentamicin loading of 1, 2, 3, or 4 g, in a cement powder mass of 40 g, resulted in a significant decrease in the compressive and four-point bending strength, but a significant increase in the amount of gentamicin released over a 72h period. When overt infection was modelled, using Staphylococcus spp. clinical isolates at an inoculum of 1 x 10(7) colony-forming units/ml, an increase in the amount of gentamicin (1, 2, 3, or 4 g) added to 40 g of poly(methyl methacrylate) cement resulted in an initial decrease in bacterial colonization but this beneficial effect was no longer apparent by 72 h, with the bacterial strains forming biofilms on the cements despite the release of high levels of gentamicin. The findings suggest that orthopaedic surgeons should carefully consider the clinical consequences of blending large doses (1 g or more per 40 g of poly(methyl methacrylate)) of gentamicin into Palacos R bone cement for use in revision surgery as the increased gentamicin loading does not prevent bacterial biofilm formation and the effect on the mechanical properties could be important to the longevity of the prosthetic joint.

Particle attrition of alpha-tricalcium phosphate: effect on mechanical, handling, and injectability properties of calcium phosphate cements.

Calcium phosphate bone cements are currently used in a range of applications; however, their low compressive strength and brittle failure mechanics have limited their widespread application. The aim of this study was to improve the mechanical performance of the calcium phosphate cement by means of particle reduction of the powder components involved. alpha-Tricalcium phosphate (alpha-TCP) powder was produced and subsequently reacted with water to form a calcium-deficient hydroxyapatite in the form of a biocompatible and resorbable cement. It was postulated that the reduction of the alpha-TCP particle size would result in a faster-setting reaction and stronger cement. Three milling techniques were explored and their methods optimized. The techniques included the traditional ball-milling technique and two newer techniques, namely cryogenic and planetary milling. Particle size analysis through laser diffraction and scanning electron microscopy was conducted. Compressive strength, setting times and injectability characteristics of the curing cement were determined. It was observed that all three techniques were efficient methods of particle reduction and the mechanical, setting and injectability properties were significantly improved by the reduction in particle size of the alpha-TCP powder. However, agglomerations of alpha-tricalcium phosphate resulted in a reduction in compressive strength and injectability after prolonged milling periods, irrespective of milling technique.

Incorporation of chitosan in acrylic bone cement: effect on antibiotic release, bacterial biofilm formation and mechanical properties.

Bacterial infection remains a significant problem following total joint replacement. Efforts to prevent recurrent implant infection, including the use of antibiotic-loaded bone cement for implant fixation at the time of revision surgery, are not always successful. In this in vitro study, we investigated whether the addition of chitosan to gentamicin-loaded Palacos R bone cement increased antibiotic release and prevented bacterial adherence and biofilm formation by Staphylococcus spp. clinical isolates. Furthermore, mechanical tests were performed as a function of time post-polymerisation in pseudo-physiological conditions. The addition of chitosan to gentamicin-loaded Palacos R bone cement significantly decreased gentamicin release and did not increase the efficacy of the bone cement at preventing bacterial colonisation and biofilm formation. Moreover, the mechanical performance of cement containing chitosan was significantly reduced after 28 days of saline degradation with the compressive and bending strengths not in compliance with the minimum requirements as stipulated by the ISO standard for PMMA bone cement. Therefore, incorporating chitosan into gentamicin-loaded Palacos R bone cement for use in revision surgery has no clinical antimicrobial benefit and the detrimental effect on mechanical properties could adversely affect the longevity of the prosthetic joint.

Ultrasonic characterization of the mechanical properties and polymerization reaction of acrylic-based bone cements.

In this investigation the pulse-echo technique was validated as a method that could be used to monitor the complete polymerization of acrylic bone cement in a surgical theatre. Currently, orthopaedic surgeons have no objective method to quantify the state of cure of bone cement as it progresses through its polymerization cycle. Clear benefits of the pulse-echo technique are that it is easy to use, non-invasive, and non-destructive. Furthermore, the test results were found to be highly reproducible with minor deviations. Three proprietary cements were used to confirm the validity of the technique; CMW Endurance, Palacos R and Simplex P. The results showed that the acoustic properties of bone cement clearly demonstrated a relationship with the different stages of polymerization, and in particular with the transitions between the waiting, dough, and setting phases. Additionally, the cure time of the poly(methyl methacrylate) cements consistently correlated with the attainment of 75 per cent of the average maximum velocity of sound value. The measured cure times concurred with the ISO and ASTM standards. Moreover, measurements of the final sound velocity and broadband ultrasonic attenuation correlated strongly with the density and mechanical properties of the cured bone cement samples.

Validation of the small-punch test as a technique for characterizing the mechanical properties of acrylic bone cement.

This paper examines the validity of using the small-punch test technique as a means of quantifying the mechanical properties of acrylic bone cement under different test conditions. The elastic moduli calculated using the small-punch test method were compared with data measured using the international standard for acrylic bone resin, ISO 5833. Conclusions from the study indicate that the small-punch test is a reproducible miniature specimen test method that can be used to characterize the mechanical properties of retrieved acrylic bone cement as used in total joint replacement surgery. Moreover, the test conditions were found to influence the elastic modulus of acrylic bone cement. The test temperature had a greater effect on the elastic behaviour of the bone cement than the test medium.

Assessment of cement introduction and pressurization techniques.

The objective of this study was to measure the medullary pressures generated during bone cement injection, pressurization and femoral prosthesis insertion. The measurements were recorded throughout the length of an in vitro femoral model while implanting a series of prosthetic hip stems using different pressurization techniques. The prostheses used were a Charnley 40 flanged stem (Johnson & Johnson DePuy International Limited), an Exeter No. 3 stem (Stryker Howmedica Osteonics, Howmedica International Limited), and a customized femoral component (Johnson & Johnson DePuy International Limited). The following parameters were derived from the pressure data recorded: peak pressure, decay pressure and duration above optimum pressure of 76 kPa to predict adequate penetration. The custom and Exeter stems generated cement pressures throughout the length of the cavity model that were predicted to achieve adequate bone cement interdigitation into cancellous bone. For all the conditions investigated in this study, when using the Charnley femoral component, an adequate level of cement pressurization was generated in the medial-distal portion of the femoral cavity. It is postulated that this could result in reduced integration of the cement mantle with bone and less effective transmission of functional loads applied during a patient's normal activity, postoperatively.

Shrinkage stresses in bone cement.

Shrinkage of bone cement is reported primarily as a consequence of polymerisation, however thermal shrinkage also occurs as a result of its exothermic reaction. It is proposed that the latter effect is important, since it occurs late in the curing cycle at a time when the cement has attained its mechanical properties as a solid, and that residual stresses result. Observations from experiments and literature reports suggest that residual stresses may be sufficient to initiate cracks at the interface between hip replacement stems and cement.A theoretical model has been developed to calculate interference stresses, using thick-walled cylinder theory, on the basis of thermal and total shrinkages. Thermal shrinkage values were calculated using the coefficient of linear thermal expansion of bone cement, while total shrinkages were measured. Moduli of elasticity values were measured for acrylic bone cements ranging from 2.1 to 2.7GPa, as were Poisson's ratio values ranging from 0.38 to 0.46. Theoretical calculation of stresses in a cement mantle, based on assumptions of thermal shrinkage alone, predicted circumferential stresses of 8.4-25.2MPa for cement curing temperatures in the range 60-140 degrees C. It is concluded that cracks observed around hip prosthesis stems in laboratory specimens of bone cement are due to shrinkage and that residual stresses are sufficient to cause crack initiation prior to functional loading.

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.

Fracture characteristics of acrylic bone cement-bone composites.

In this study, the fracture properties of Perspex, acrylic bone cement prepared using a commercially available reduced pressure mixing system and a bone cement-bone composite were compared under different test conditions. The method used was the double-torsion (DT) test. The observations made from this investigation are as follows. The fracture toughness and critical crack length for Perspex significantly increased (ANOVA, p = 0.001) when tested in water compared to air. An increase in test temperature from 19 to 37 degrees C resulted in a decrease in the fracture properties in water, this reduction being also statistically significant (ANOVA, p = 0.02). The mean fracture toughness and standard deviation of CMW3 bone cement when mixed under reduced pressure was 2.19 +/- 0.11 MN m(-3/2) compared to 3.89 +/- 0.10 MN m(-3/2) for the cement-bone composite (ANOVA, p = 0.004). The crack length determined for CMW3 bone cement and the cement bone composite were 0.323 +/- 0.031 and 1.1434 +/- 0.61 mm respectively. The plateau loads of the composite material were higher than measured for the monolithic acrylic bone cement, 249.66 +/- 67.75 N compared with 140.83 +/- 6.82 N. The high level of variation recorded for the plateau loads of the bone cement bone composite is due to the orientation and volume fraction of the cancellous bone. It can be concluded from this investigation that acrylic bone cement interdigitation into the cancellous bone results in a superior material with respect to crack resistance in comparison with the bone cement as a lone entity. Therefore it is an advantage if there is sufficient cancellous bone stock available within the intermedullary canal to allow bone cement penetration to occur, for the transfer of loads during daily activity. Additionally, it is paramount that the clinician ensures that adequate pressure is applied and maintained for an appropriate time during cement injection and prosthesis insertion in order to ensure optimum cement penetration into the pore openings of the cancellous bone, thus improving the resistance of the cement mantle to fracture and ultimately improving the longevity of the joint replacement.

Curing characteristics of acrylic bone cement.

Commercial acrylic bone cements are supplied as two components, a polymer powder and a liquid monomer. Mixing of the two components is followed by a progressive polymerization of the liquid monomer to yield a solid mass, a high level of heat being generated during this exothermic reaction. The exposure of bone to high temperatures has led to incidences of bone necrosis and tissue damage, ultimately resulting in failure of the prosthetic fixation. The aim of this study was to determine the thermal properties of two acrylic bone cements as they progress through their polymerization cycles. It was also felt that there was a need to quantify the variations in the curing characteristics as a function of preparing bone cement by different techniques, hand mixing and vacuum mixing. A number of parameters were calculated using the data gathered from the investigation: peak temperature, cure temperature, cure time, and the cumulative thermal necrosis damage index. The results show the temperature profile recorded during polymerization was lowest when the cement was prepared using the Howmedica Mix-Kit I system: 36 degrees C for Palacos R and 41 degrees C for CMW3 respectively. When the acrylic cements were prepared in any vacuum mixing system there was evidence of an increase in the cure temperature. The main factor that contributed to this rise in temperature was an imbalance in the polymer powder : liquid monomer ratio, there was a high incidence of unmixed powder visible in the mixing barrel of some contemporary vacuum mixing devices. Observing the thermal characteristics of the polymethyl methacrylate (PMMA) bone cements assessed, it was found that particular formulations of bone cements are suited to certain mixing methodologies. It is vital that a full investigation is conducted on a cement mixing/delivery system prior to its introduction into the orthopaedic market.