A novel injectable borate bioactive glass cement for local delivery of vancomycin to cure osteomyelitis and regenerate bone.

Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting time = 5.8 ± 0.6 min; compressive strength = 25.6 ± 0.3 MPa) released vancomycin over ~25 days in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8 weeks. Osteomyelitis was cured in 87 % of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71 % for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection.

In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites.

Borate bioactive glass-based composites have been attracting interest recently as an osteoconductive carrier material for local antibiotic delivery. In the present study, composites composed of borate bioactive glass particles bonded with a chitosan matrix were prepared and evaluated in vitro as a carrier for gentamicin sulfate. The bioactivity, degradation, drug release profile, and compressive strength of the composite carrier system were studied as a function of immersion time in phosphate-buffered saline at 37 °C. The cytocompatibility of the gentamicin sulfate-loaded composite carrier was evaluated using assays of cell proliferation and alkaline phosphatase activity of osteogenic MC3T3-E1 cells. Sustained release of gentamicin sulfate occurred over ~28 days in PBS, while the bioactive glass converted continuously to hydroxyapatite. The compressive strength of the composite loaded with gentamicin sulfate decreased from the as-fabricated value of 24 ± 3 MPa to ~8 MPa after immersion for 14 days in PBS. Extracts of the soluble ionic products of the borate glass/chitosan composites enhanced the proliferation and alkaline phosphatase activity of MC3T3-E1 cells. These results indicate that the gentamicin sulfate-loaded composite composed of chitosan-bonded borate bioactive glass particles could be useful clinically as an osteoconductive carrier material for treating bone infection.

Hollow hydroxyapatite microspheres as a device for controlled delivery of proteins.

Hollow hydroxyapatite (HA) microspheres were prepared by reacting solid microspheres of Li(2)O-CaO-B(2)O(3) glass (106-150 µm) in K(2)HPO(4) solution, and evaluated as a controlled delivery device for a model protein, bovine serum albumin (BSA). Reaction of the glass microspheres for 2 days in 0.02 M K(2)HPO(4) solution (pH = 9) at 37°C resulted in the formation of biocompatible HA microspheres with a hollow core diameter equal to 0.6 the external diameter, high surface area (~100 m(2)/g), and a mesoporous shell wall (pore size ≈ 13 nm). After loading with a solution of BSA in phosphate-buffered saline (PBS) (5 mg BSA/ml), the release kinetics of BSA from the HA microspheres into a PBS medium were measured using a micro bicinchoninic acid (BCA) protein assay. Release of BSA initially increased linearly with time, but almost ceased after 24-48 h. Modification of the BSA release kinetics was achieved by modifying the microstructure of the as-prepared HA microspheres using a controlled heat treatment (1-24 h at 600-900°C). Sustained release of BSA was achieved over 7-14 days from HA microspheres heated for 5 h at 600°C. The amount of BSA released at a given time was dependent on the concentration of BSA initially loaded into the HA microspheres. These hollow HA microspheres could provide a novel inorganic device for controlled local delivery of proteins and drugs.

Freeze extrusion fabrication of 13-93 bioactive glass scaffolds for bone repair.

A solid freeform fabrication technique, freeze extrusion fabrication (FEF), was investigated for the creation of three-dimensional bioactive glass (13-93) scaffolds with pre-designed porosity and pore architecture. An aqueous mixture of bioactive glass particles and polymeric additives with a paste-like consistency was extruded through a narrow nozzle, and deposited layer-by-layer in a cold environment according to a computer-aided design (CAD) file. Following sublimation of the ice in a freeze dryer, the construct was heated according to a controlled schedule to burn out the polymeric additives (below ~500°C), and to densify the glass phase at higher temperature (1 h at 700°C). The sintered scaffolds had a grid-like microstructure of interconnected pores, with a porosity of ~50%, pore width of ~300 µm, and dense glass filaments (struts) with a diameter or width of ~300 µm. The scaffolds showed an elastic response during mechanical testing in compression, with an average compressive strength of 140 MPa and an elastic modulus of 5-6 GPa, comparable to the values for human cortical bone. These bioactive glass scaffolds created by the FEF method could have potential application in the repair of load-bearing bones.

Effect of pyrophosphate ions on the conversion of calcium-lithium-borate glass to hydroxyapatite in aqueous phosphate solution.

The conversion of glass to a hydroxyapatite (HA) material in an aqueous phosphate solution is used as an indication of the bioactive potential of the glass, as well as a low temperature route for preparing biologically useful materials. In this work, the effect of varying concentrations of pyrophosphate ions in the phosphate solution on the conversion of a calcium-lithium-borate glass to HA was investigated. Particles of the glass (150-355 µm) were immersed for up to 28 days in 0.25 M K(2)HPO(4) solution containing 0-0.1 M K(4)P(2)O(7). The kinetics of degradation of the glass particles and their conversion to HA were monitored by measuring the weight loss of the particles and the ionic concentration of the solution. The structure and composition of the conversion products were analyzed using X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. For K(4)P(2)O(7) concentrations of up to 0.01 M, the glass particles converted to HA, but the time for complete conversion increased from 2 days (no K(4)P(2)O(7)) to 10 days (0.01 M K(4)P(2)O(7)). When the K(4)P(2)O(7) concentration was increased to 0.1 M, the product consisted of an amorphous calcium phosphate material, which eventually crystallized to a pyrophosphate product (predominantly K(2)CaP(2)O(7) and Ca(2)P(2)O(7)). The consequences of the results for the formation of HA materials and devices by the glass conversion route are discussed.

Mechanical and degradation properties of poly(methyl methacrylate) cement/borate bioactive glass composites.

Bone cement is used extensively in orthopedics to anchor prostheses to bone and fill voids. Incorporating bioactive glass into poly(methyl methacrylate) (PMMA)-based bone cement could potentially improve its effectiveness for these tasks. This study characterizes the mechanical and degradation properties of composites containing PMMA-based bone cement and particles of borate bioactive glass designated as 13-93B3. Glass particles of size 5, 33, and 100 µm were mixed with PMMA bone cement to create composites containing 20, 30, and 40 wt % glass. Composites and a bone cement control were soaked in phosphate-buffered saline. Compressive strength, Young's modulus, weight loss, water uptake, solution pH, and ionic concentrations were measured over 21 days. The compressive strengths of composites decreased over 21 days. Average Young's moduli of the composites remained below 3 GPa. Weight loss and water uptake of specimens did not exceed 2 and 6%, respectively. Boron concentrations and pH of all solutions increased over time, with higher glass weight fractions leading to higher pH values. Results demonstrated that the composite can sustain glass degradation and ionic release without compromising short-term mechanical strength.

Characterization of the conversion of bone cement and borate bioactive glass composites.

Borate bioactive glass 13-93B3 converts into an osteoconductive hydroxyapatite-like material in a liquid medium. In this study, 13-93B3 was incorporated into a commercial PMMA (poly(methyl methacrylate)) bone cement, and the conversion of the glass into a precipitate in solution was investigated with scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared (spectroscopy)-attenuated total reflection, and micro-Raman spectroscopy. Glass particles of 5, 33, and 100 µm diameter were each mixed with the PMMA cement to create 20, 30, and 40% glass-loaded composites. Precipitate formation was found to be a calcium-deficient apatite partially substituted with magnesium ions that resembles native bone material and would ideally encourage bone growth better than stoichiometric hydroxyapatite. Composites of bone cement and 13-93B3 show promise as a means of encouraging bone attachment to the surface of the bone cement.

Proliferation and function of MC3T3-E1 cells on freeze-cast hydroxyapatite scaffolds with oriented pore architectures.

Previous work by the authors showed that hydroxyapatite (HA) scaffolds with different types of oriented microstructures and a unique 'elastic-plastic' mechanical response could be prepared by unidirectional freezing of suspensions. The objective of the present work was to evaluate the in vitro cellular response to these freeze-cast HA scaffolds. Unidirectional scaffolds with approximately the same porosity (65-70%) but different pore architectures, described as 'lamellar' (pore width = 25 +/- 5 microm) and 'cellular' (pore diameter = 100 +/- 10 microm), were evaluated. Whereas both groups of scaffolds showed excellent ability to support the proliferation of MC3T3-E1 pre-osteoblastic cells on their surfaces, scaffolds with the cellular-type microstructure showed far better ability to support cell proliferation into the pores and cell function. These results indicate that freeze-cast HA scaffolds with the cellular-type microstructure have better potential for bone repair applications.

Fabrication and testing of silicon nitride bearings in total hip arthroplasty: winner of the 2007 "HAP" PAUL Award.

Total hip arthroplasty (THA) bearings were fabricated from silicon nitride (Si(3)N(4)) powder. Mechanical testing showed that Si(3)N(4) had improved fracture toughness and fracture strength over modern alumina (Al(2)O(3)) ceramic. When tested with Si(3)N(4) cups in a hip simulator, both cobalt-chromium (CoCr) and Si(3)N(4) femoral heads produced low wear rates that were comparable to Al(2)O(3)-Al(2)O(3) bearings in THA. This study offers experimental support for a novel metal-ceramic THA bearing couple that combines the reliability of CoCr femoral heads with the wear advantages of ceramic surfaces.

Growth and differentiation of osteoblastic cells on 13-93 bioactive glass fibers and scaffolds.

This in vitro study was conducted to evaluate the ability of two types of constructs of bioactive, silica-based 13-93 glass fibers to support the growth and differentiation of MC3T3-E1 osteoblastic cells. The two types of constructs tested included single-layer 13-93 glass fiber rafts and three-dimensional porous scaffolds formed from sintered 13-93 fibers. Scanning electron micrographs showed a closely adhering, well-spread morphology of MC3T3-E1 cells seeded on both types of constructs. The scanning electron microscopy images also showed a continuous increase in cell densities during a 6 day incubation on 13-93 glass fiber rafts and scaffolds. Quantitative fluorescence measurements of DNA also revealed a linear increase in cell density during a 6 day incubation on both types of 13-93 constructs. Examination of scaffolds incubated in MTT containing medium showed the presence of metabolically active viable cells within the interior of the scaffold. The addition of ascorbic acid to MC3T3-E1 cells cultured on the 13-93 glass fibers triggered a threefold increase in alkaline phosphatase, a key indicator of osteoblast differentiation. The sintered scaffolds were found to have open, interconnected pores favorable for tissue ingrowth with a compressive strength similar to cancellous bone. Collectively, the results indicate that 13-93 glass fiber scaffolds are a favorable substrate for the growth and differentiation of osteoblasts and a promising material for bone tissue engineering and repair of bone defects.

In vitro study on different cell response to spherical hydroxyapatite nanoparticles.

Hydroxyapatite (HA) is widely used in filling of bone defects and coating on metal parts of prosthetic implants due to its excellent biocompatibility, bioactivity, and bone-bonding properties. It has been demonstrated that micro-sized HA particles cause inflammatory reaction, especially for the needle shaped particles. However, little effort has been concentrated on the cell responses of the spherical HA nanoparticles. The aim of the present work is to chemically and physically characterize the synthesized HA nanoparticles and to investigate the in vitro cell responses. X-ray diffraction, electron microscopy, nitrogen adsorption, and Fourier transform infrared spectroscopy revealed that the particles consisted of nearly spherical crystallites of carbonate-substituted HA with size of 20-40 nm and specific surface area of 75 m(2)/g. L929 cell proliferation experiments demonstrate that the spherical HA nanoparticles is more biocompatible than commercially available HA. On the other hand, U2-OS cell test results show that the inhibition rate of the spherical HA nanoparticles increases with time and concentration. The half effective inhibitory concentration (IC50) of the nanoparticles was determined to be 50.8 mug/mL at 72 h. All these data indicated that the synthesized spherical nanocrystalline HA particles can function as an effective biomaterial for bone tumorectomy repair, while having little adverse effect.

Preparation and bioactive characteristics of a porous 13-93 glass, and fabrication into the articulating surface of a proximal tibia.

The silicate-based 45S5 bioactive glass, typically in particulate form, has been widely investigated for bone repair. However, its application as a scaffold for bone tissue engineering is limited due to the difficulty of forming porous three-dimensional constructs with complex shapes. In this study, the use of another silicate-based bioactive glass, referred to as 13-93, was investigated for the preparation of porous constructs. Particles of 13-93 glass (255-325 microm) were consolidated and sintered to form cylindrical constructs. Characterization of these constructs was performed using mercury porosimetry, scanning electron microscopy (SEM), and mechanical testing. Constructs with porosities of 40-45% and pore sizes in the range 100-300 microm were found to have a compressive strength of 22 +/- 1 MPa. The bioactivity of the 13-93 glass was studied by immersing disks in a simulated body fluid at 37 degrees C and characterizing the reaction products. X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, and SEM showed the formation of a crystalline hydroxyapatite layer on the glass surface after approximately 7 days. The ability to fabricate the complex geometrical shape of the articulating surface of a human tibia from 13-93 glass particles was demonstrated.

Enhanced osteointegration of poly(methylmethacrylate) bone cements by incorporating strontium-containing borate bioactive glass.

Although poly(methylmethacrylate) (PMMA) cements are widely used in orthopaedics, they have numerous drawbacks. This study aimed to improve their bioactivity and osseointegration by incorporating strontium-containing borate bioactive glass (SrBG) as the reinforcement phase and bioactive filler of PMMA cement. The prepared SrBG/PMMA composite cements showed significantly decreased polymerization temperature when compared with PMMA and retained properties of appropriate setting time and high mechanical strength. The bioactivity of SrBG/PMMA composite cements was confirmed in vitro, evidenced by ion release (Ca, P, B and Sr) from SrBG particles. The cellular responses of MC3T3-E1 cells in vitro demonstrated that SrBG incorporation could promote adhesion, migration, proliferation and collagen secretion of cells. Furthermore, our in vivo investigation revealed that SrBG/PMMA composite cements presented better osseointegration than PMMA bone cement. SrBG in the composite cement could stimulate new-bone formation around the interface between the composite cement and host bone at eight and 12 weeks post-implantation, whereas PMMA bone cement only stimulated development of an intervening connective tissue layer. Consequently, the SrBG/PMMA composite cement may be a better alternative to PMMA cement in clinical applications and has promising orthopaedic applications by minimal invasive surgery.

Evaluation of an injectable bioactive borate glass cement to heal bone defects in a rabbit femoral condyle model.

There is a need for synthetic biomaterials to heal bone defects using minimal invasive surgery. In the present study, an injectable cement composed of bioactive borate glass particles and a chitosan bonding solution was developed and evaluated for its capacity to heal bone defects in a rabbit femoral condyle model. The injectability and setting time of the cement in vitro decreased but the compressive strength increased (8±2MPa to 31±2MPa) as the ratio of glass particles to chitosan solution increased (from 1.0gml-1 to 2.5gml-1). Upon immersing the cement in phosphate-buffered saline, the glass particles reacted and converted to hydroxyapatite, imparting bioactivity to the cement. Osteoblastic MC3T3-E1 cells showed enhanced proliferation and alkaline phosphatase activity when incubated in media containing the soluble ionic product of the cement. The bioactive glass cement showed a better capacity to stimulate bone formation in rabbit femoral condyle defects at 12weeks postimplantation when compared to a commercial calcium sulfate cement. The injectable bioactive borate glass cement developed in this study could provide a promising biomaterial to heal bone defects by minimal invasive surgery.

Preparation of resorbable carbonate-substituted hollow hydroxyapatite microspheres and their evaluation in osseous defects in vivo.

Hollow hydroxyapatite (HA) microspheres, with a high-surface-area mesoporous shell, can provide a unique bioactive and osteoconductive carrier for proteins to stimulate bone regeneration. However, synthetic HA has a slow resorption rate and a limited ability to remodel into bone. In the present study, hollow HA microspheres with controllable amounts of carbonate substitution (0-12 wt.%) were created using a novel glass conversion route and evaluated in vitro and in vivo. Hollow HA microspheres with ~12 wt.% of carbonate (designated CHA12) showed a higher surface area (236 m(2) g(-1)) than conventional hollow HA microspheres (179 m(2)g(-1)) and a faster degradation rate in a potassium acetate buffer solution. When implanted for 12 weeks in rat calvarial defects, the CHA12 and HA microspheres showed a limited capacity to regenerate bone but the CHA12 microspheres resorbed faster than the HA microspheres. Loading the microspheres with bone morphogenetic protein-2 (BMP2) (1 µg per defect) stimulated bone regeneration and accelerated resorption of the CHA12 microspheres. At 12 weeks, the amount of new bone in the defects implanted with the CHA12 microspheres (73±8%) was significantly higher than the HA microspheres (59±2%) while the amount of residual CHA12 microspheres (7±2% of the total defect area) was significantly lower than the HA microspheres (21±3%). The combination of these carbonate-substituted HA microspheres with clinically safe doses of BMP2 could provide promising implants for healing non-loaded bone defects.

Effect of copper-doped silicate 13-93 bioactive glass scaffolds on the response of MC3T3-E1 cells in vitro and on bone regeneration and angiogenesis in rat calvarial defects in vivo.

The release of inorganic ions from biomaterials could provide an alternative approach to the use of growth factors for improving tissue healing. In the present study, the release of copper (Cu) ions from bioactive silicate (13-93) glass scaffolds on the response of cells in vitro and on bone regeneration and angiogenesis in vivo was studied. Scaffolds doped with varying concentrations of Cu (0-2.0wt.% CuO) were created with a grid-like microstructure by robotic deposition. When immersed in simulated body fluid in vitro, the Cu-doped scaffolds released Cu ions into the medium in a dose-dependent manner and converted partially to hydroxyapatite. The proliferation and alkaline phosphatase activity of pre-osteoblastic MC3T3-E1 cells cultured on the scaffolds were not affected by 0.4 and 0.8wt.% CuO in the glass but they were significantly reduced by 2.0wt.% CuO. The percent new bone that infiltrated the scaffolds implanted for 6weeks in rat calvarial defects (46±8%) was not significantly affected by 0.4 or 0.8wt.% CuO in the glass whereas it was significantly inhibited (0.8±0.7%) in the scaffolds doped with 2.0wt.% CuO. The area of new blood vessels in the fibrous tissue that infiltrated the scaffolds increased with CuO content of the glass and was significantly higher for the scaffolds doped with 2.0wt.% CuO. Loading the scaffolds with bone morphogenetic protein-2 (1µg/defect) significantly enhanced bone infiltration and reduced fibrous tissue in the scaffolds. These results showed that doping the 13-93 glass scaffolds with up to 0.8wt.% CuO did not affect their biocompatibility whereas 2.0wt.% CuO was toxic to cells and detrimental to bone regeneration.

Surface modulation of silicon nitride ceramics for orthopaedic applications.

Silicon nitride (Si3N4) has a distinctive combination of material properties such as high strength and fracture toughness, inherent phase stability, scratch resistance, low wear, biocompatibility, hydrophilic behavior, excellent radiographic imaging and resistance to bacterial adhesion, all of which make it an attractive choice for orthopaedic implants. Unlike oxide ceramics, the surface chemistry and topography of Si3N4 can be engineered to address potential in vivo needs. Morphologically, it can be manufactured to have an ultra-smooth or highly fibrous surface structure. Its chemistry can be varied from that of a silica-like surface to one which is predominately comprised of silicon-amines. In the present study, a Si3N4 bioceramic was subjected to thermal, chemical, and mechanical treatments in order to induce changes in surface composition and features. The treatments included grinding and polishing, etching in aqueous hydrofluoric acid, and heating in nitrogen or air. The treated surfaces were characterized using a variety of microscopy techniques to assess morphology. Surface chemistry and phase composition were determined using X-ray photoelectron and Raman spectroscopy, respectively. Streaming potential measurements evaluated surface charging, and sessile water drop techniques assessed wetting behavior. These treatments yielded significant differences in surface properties with isoelectric points ranging from 2 to 5.6, and moderate to extremely hydrophilic water contact angles from ∼65° to ∼8°. This work provides a basis for future in vitro and in vivo studies which will examine the effects of these treatments on important orthopaedic properties such as friction, wear, protein adsorption, bacteriostasis and osseointegration. STATEMENT OF SIGNIFICANCE: Silicon nitride (Si3N4) exhibits a unique combination of bulk mechanical and surface chemical properties that make it an ideal biomaterial for orthopaedic implants. It is already being used for interbody spinal fusion cages and is being developed for total joint arthroplasty. Its surface texture and chemistry are both highly tunable, yielding physicochemical combinations that may lead to enhanced osseointegration and bacterial resistance without compromising bulk mechanical properties. This study demonstrates the ease with which significant changes to Si3N4's surface phase composition, charging, and wetting behavior can be induced, and represents an initial step towards a mechanistic understanding of the interaction between implant surfaces and the biologic environment.

Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal full-thickness skin defects in a rodent model.

There is a need for better wound dressings that possess the requisite angiogenic capacity for rapid in situ healing of full-thickness skin wounds. Borate bioactive glass microfibers are showing a remarkable ability to heal soft tissue wounds but little is known about the process and mechanisms of healing. In the present study, wound dressings composed of borate bioactive glass microfibers (diameter = 0.4-1.2 µm; composition 6Na2O, 8K2O, 8MgO, 22CaO, 54B2O3, 2P2O5; mol%) doped with 0-3.0 wt.% CuO were created and evaluated in vitro and in vivo. When immersed in simulated body fluid, the fibers degraded and converted to hydroxyapatite within ∼7 days, releasing ions such as Ca, B and Cu into the medium. In vitro cell culture showed that the ionic dissolution product of the fibers was not toxic to human umbilical vein endothelial cells (HUVECs) and fibroblasts, promoted HUVEC migration, tubule formation and secretion of vascular endothelial growth factor (VEGF), and stimulated the expression of angiogenic-related genes of the fibroblasts. When used to treat full-thickness skin defects in rodents, the Cu-doped fibers (3.0 wt.% CuO) showed a significantly better capacity to stimulate angiogenesis than the undoped fibers and the untreated defects (control) at 7 and 14 days post-surgery. The defects treated with the Cu-doped and undoped fibers showed improved collagen deposition, maturity and orientation when compared to the untreated defects, the improvement shown by the Cu-doped fibers was not markedly better than the undoped fibers at 14 days post-surgery. These results indicate that the Cu-doped borate glass microfibers have a promising capacity to stimulate angiogenesis and heal full-thickness skin defects. They also provide valuable data for understanding the role of the microfibers in healing soft tissue wounds.

Evaluation of injectable strontium-containing borate bioactive glass cement with enhanced osteogenic capacity in a critical-sized rabbit femoral condyle defect model.

The development of a new generation of injectable bone cements that are bioactive and have enhanced osteogenic capacity for rapid osseointegration is receiving considerable interest. In this study, a novel injectable cement (designated Sr-BBG) composed of strontium-doped borate bioactive glass particles and a chitosan-based bonding phase was prepared and evaluated in vitro and in vivo. The bioactive glass provided the benefits of bioactivity, conversion to hydroxyapatite, and the ability to stimulate osteogenesis, while the chitosan provided a cohesive biocompatible and biodegradable bonding phase. The Sr-BBG cement showed the ability to set in situ (initial setting time = 11.6 ± 1.2 min) and a compressive strength of 19 ± 1 MPa. The Sr-BBG cement enhanced the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro when compared to a similar cement (BBG) composed of chitosan-bonded borate bioactive glass particles without Sr. Microcomputed tomography and histology of critical-sized rabbit femoral condyle defects implanted with the cements showed the osteogenic capacity of the Sr-BBG cement. New bone was observed at different distances from the Sr-BBG implants within eight weeks. The bone-implant contact index was significantly higher for the Sr-BBG implant than it was for the BBG implant. Together, the results indicate that this Sr-BBG cement is a promising implant for healing irregularly shaped bone defects using minimally invasive surgery.

Comparison of the response of primary human blood monocytes and the U937 human monocytic cell line to two different sizes of alumina ceramic particles.

It is well recognized that wear particles derived from orthopaedic implants have the potential to induce inflammation, which may eventually lead to aseptic loosening of the artificial joint. We hypothesized that alumina ceramic particles of different sizes cause a differential cytokine response by human monocytes. To test this hypothesis a human monocytic cell line (U937) and primary human blood monocytes obtained from healthy volunteers were exposed to ceramic particles within the range known to be generated in vivo. Cellular responses were measured by quantifying the relative gene expression of 12 different cytokines using TAQman Real-Time Polymerase Chain Reaction (RT-PCR). Our results demonstrate that at a particle to cell ratio of 100:1, 0.5 microm ceramic particles consistently provoked higher amounts of Interleukin-1alpha (IL-1alpha), IL-1beta, IL-8, IL-10 and Tumor necrosis factor-alpha (TNF-alpha) steady state mRNA by U937 cells. As expected, the variability of cytokine expression in primary blood monocytes was much higher compared to the cell line however, a similar trend was observed. These results show a differential response to ceramic particle size, which may imply that 0.5 microm particles are less biocompatible. New ceramic implants can be designed to generate a known particle size range in vivo. Implant materials of this type may induce relatively lower levels of production of inflammatory cytokines resulting in a reduced incidence of failure due to aseptic loosening.