Evaluation of two novel aluminum-free,zinc-based glass polyalkenoate cements as alternatives to PMMA bone cement for use in vertebroplasty and balloon kyphoplasty

Vertebroplasty (VP) and balloon kyphoplasty (BKP) are now widely used for treating patients in whom the pain due to vertebral compression fractures is severe and has proved to be refractory to conservative treatment. These procedures involve percutaneous delivery of a bolus of an injectable bone cement either directly to the fractured vertebral body, VB (VP) or to a void created in it by an inflatable bone tamp (BKP). Thus, the cement is a vital component of both procedures. In the vast majority of VPs and BKPs, a poly(methyl methacrylate) (PMMA) bone cement is used. This material has many shortcomings, notably lack of bioactivity and very limited resorbability. Thus, there is room for alternative cements. We report here on two variants of a novel, bioactive, Al-free, Zn-based glass polyalkenoate cement (Zn-GPC), and how their properties compare to those of an injectable PMMA bone cement (SIMPL) that is widely used in VP and BKP. The properties determined were injectability, radiopacity, uniaxial compressive strength, and biaxial flexural modulus. In addition, we compared the compression fatigue lives of a validated synthetic osteoporotic VB model (a polyurethane foam cube with an 8 mm-diameter through-thickness cylindrical hole), at 0–2300 N and 3 Hz, when the hole was filled with each of the three cements. A critical review of the results suggests that the performance of each of the Zn-GPCs is comparable to that of SIMPL; thus, the former cements merit further study with a view to being alternatives to an injectable PMMA cement for use in VP and BKP.     

Synthesis of bioactive PMMA bone cement via modification with methacryloxypropyltri- methoxysilane and calcium acetate

Bone cement consisting of polymethylmethacrylate (PMMA) powder and methylmethacrylate (MMA) liquid is clinically used for fixation of implants such as artificial hip joints. However, it does not show bone-bonding ability, i.e., bioactivity. The lack of bioactivity would be one of factors which cause loosening between the cement and the implant. The present authors recently showed the potential of bioactive PMMA-based bone cement through modification with γ -methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. In this study, the effects of the kinds of PMMA powder on setting time, apatite formation and compressive strength were investigated in a simulated body fluid (Kokubo solution). The cement modified with calcium acetate calcined at 220 ^∘C could set within 15 min when the PMMA powder had an average molecular weight of 100,000 or less. The addition of calcium acetate calcined at 120 ^∘C in the PMMA powder required a much longer period for setting. The modified cements formed an apatite layer after soaking in the Kokubo solution within 1 day for cement starting from PMMA powder with a molecular weight of 100,000 or less. Compressive strengths of the modified cements were more than 70 MPa for cements starting from 100,000 and 56,000 in molecular weight. After soaking in Kokubo solution for 7 days, the modified cement consisting of PMMA powder of 100,000 in molecular weight showed a smaller decrease in compressive strength than that consisting of 56,000 in molecular weight. These results indicate that bioactive PMMA cement can be produced with appropriate setting time and mechanical strength when PMMA powders with a suitable molecular weight are used. Such a type of design of bioactive PMMA bone cement leads to a novel development of bioactive material for bone substitutes.     

Osteoclastic cell behaviors affected by the α-tricalcium phosphate based bone cements

Calcium phosphate cements (CPCs) have recently gained great interest as injectable bone substitutes for use in dentistry and orthopedics. α-tricalcium phosphate (α-TCP) is a popularly used precursor powder for CPCs. When mixed with appropriate content of liquid and kept under aqueous conditions, α-TCP dissolves to form a calcium-deficient hydroxyapatite and then hardens to cement. In this study, α-TCP based cement (CP) and its composite cement with chitosan (Ch-CP) were prepared and the osteoclastic responses to the cements and their elution products were evaluated. Preliminary evaluation of the cements revealed that the CP and Ch-CP hardened within ~10 min at an appropriate powder-to-liquid ratio (PL) of 3.0. In addition, CP and Ch-CP were transformed into an apatite phase following immersion in a saline solution. Moreover, the osteoblastic cells were viable on the cements for up to 10 days. Mouse-derived bone marrow cells were isolated and activated with osteoclastic differentiation medium, and the effects of the CP and Ch-CP substrates and their ionic eluants on the osteoclastic activity were investigated. Osteoclastic cells were viable for up to 14 days on both types of cements, maintaining a higher cell growth level than the control culture dish. Multi-nucleated osteoclastic cells that were tartrate-resistant acid phosphatase (TRAP)-positive were clearly observed when cultured on the cement substrates as well as treated with the cement eluants. The TRAP activity was found to be significantly higher in cells influenced by the cement substrates and their eluants with respect to the control culture dish (Ch-CP > CP ≫ control). Overall, the osteoclastic differentiation was highly stimulated by the α-TCP based experimental cements in terms of both the substrate interaction and their elution products.     

Relationship between apatite-forming ability and mechanical properties of bioactive PMMA-based bone cement modified with calcium salts and alkoxysilane

Polymethylmethacrylate (PMMA)-based bone cement is used for the fixation of artificial joints in orthopaedics. However, the fixation is liable to loosen in the body, because the cement does not bond to living bone. So-called bioactive ceramics bond directly to living bone through the apatite layer formed on their surfaces in the body. We previously revealed that modification using γ-methacryloxypropyltrimethoxysilane (MPS) and water-soluble calcium salts such as calcium acetate and calcium hydroxide was effective for providing the PMMA-based bone cement with apatite-forming ability in a simulated body fluid (SBF, Kokubo solution) that closely reproduces the body environment. However, the effect of the chemical reaction forming the apatite on the mechanical properties of the cements has not been clarified. The present work aimed to investigate this issue from the viewpoint of the interface structure between the apatite and the cement. The surface of the cement modified with calcium acetate and MPS was fully covered with newly formed apatite after soaking in Kokubo solution within 7 days, while half of the surface area of the cement modified with calcium hydroxide and MPS was covered with the apatite. The bending strength of the modified cements decreased after soaking in Kokubo solution. Porous structure was observed in the region about 50–100 μm in depth from the top surface because of release of the Ca²⁺ ions by both modified cements after soaking in Kokubo solution. The decrease in bending strength of the modified cements could be attributed to the formation of the pores. In addition, the pores on the top surfaces of the cements were filled with the newly formed apatite. The apatite formation would be effective not only for bioactivity but also for decreasing the reduction of mechanical strength.     

Injectable Bone Cement Reinforced with Gold Nanodots Decorated rGO-Hydroxyapatite Nanocomposites,Augment Bone Regeneration

Interest in the development of new generation injectable bone cements having appropriate mechanical properties, biodegradability, and bioactivity has been rekindled with the advent of nanoscience. Injectable bone cements made with calcium sulfate (CS) are of significant interest, owing to its compatibility and optimal self-setting property. Its rapid resorption rate, lack of bioactivity, and poor mechanical strength serve as a deterrent for its wide application. Herein, a significantly improved CS-based injectable bone cement (modified calcium sulfate termed as CS_mod), reinforced with various concentrations (0–15%) of a conductive nanocomposite containing gold nanodots and nanohydroxyapatite decorated reduced graphene oxide (rGO) sheets (AuHp@rGO), and functionalized with vancomycin, is presented. The piezo-responsive cement exhibits favorable injectability and setting times, along with improved mechanical properties. The antimicrobial, osteoinductive, and osteoconductive properties of the CS_mod cement are confirmed using appropriate in vitro studies. There is an upregulation of the paracrine signaling mediated crosstalk between mesenchymal stem cells and human umbilical vein endothelial cells seeded on these cements. The ability of CS_mod to induce endothelial cell recruitment and augment bone regeneration is evidenced in relevant rat models. The results imply that the multipronged activity exhibited by the novel-CS_mod cement would be beneficial for bone repair.     

Improved mechanical properties of acrylic bone cement with short titanium fiber reinforcement

Acrylic bone cements are widely used in total joint arthroplasties to grout the prosthesis to bone. The changes in the tensile properties and fracture toughness of polymethylmethacrylate (PMMA) bone cements obtained by the addition of control and heat treated short titanium fibers are studied. Heat treatment of titanium fibers is conducted to precipitate titania particles on the fiber surface, which may improve the biocompatibility of the metal. Control (non-heat treated) and heat treated short titanium fibers (250 μm long and 20μm diameter) were used as reinforcements at 3 volume %. X-ray diffraction indicated the presence of a rutile form of titania due to the heat treatments. Results indicate that the tensile and fracture properties of unfilled bone cement were improved by the addition of control and heat-treated fibers. The fracture properties of bone cements reinforced with control titanium fibers were at least 10% higher than those reinforced with heat treated titanium fibers. Therefore, we recommend further studies on the use of non-heat treated titanium fibers to reinforce acrylic bone cement.     

Influence of ibuprofen addition on the properties of a bioactive bone cement

Bioactive bone cements can promote bone growth and the formation of a strong chemical bond between the implant and bone tissue increasing the lifetime of the prosthesis. This study aims at synthesizing a new bioactive bone cement with different amounts of ibuprofen (5, 10 and 20 wt%) using a low toxicity activator, and investigating its in vitro release profile. The effect of ibuprofen (IB) on the setting parameters, residual monomer and bioactivity in synthetic plasma was also evaluated. It was verified that the different IB contents do not prevent the growth of calcium phosphate aggregates on composite surfaces, confirming that the cements are potentially bioactive. A relevant advantage of these formulations was a significant improvement in their curing parameters with increasing IB amount, associated to a reduction of the peak temperature and an extension of the setting time. The investigated cements released an average of about 20 % of the total incorporated ibuprofen during 30 days test, with IB20 liberating the highest percentage of drug 20.6 %, and IB10 and IB5, respectively 19.1 and 17.6 %. This behavior was attributed to the low solubility of this drug in aqueous media and was also related with the hydrophobic character of the polymer. Regarding the therapeutic concentration sufficient to suppress inflammation, the cement with 10 % of ibuprofen achieved the required release rate for 1 week and the cement with 20 % for 2 weeks.     

Performance of bioactive PMMA-based bone cement under load-bearing conditions: an in vivo evaluation and FE simulation

In the past, bioactive bone cement was investigated in order to improve the durability of cemented arthroplasties by strengthening the bone-cement interface. As direct bone–cement bonding may theoretically lead to higher stresses within the cement, the question arises, whether polymethylmethacrylate features suitable mechanical properties to withstand altered stress conditions? To answer this question, in vivo experiments and finite element simulations were conducted. Twelve rabbits were divided into two groups examining either bioactive polymethylmethacrylate-based cement with unchanged mechanical properties or commercially available polymethylmethacrylate cement. The cements were tested under load-bearing conditions over a period of 7?months, using a spacer prosthesis cemented into the femur. For the finite element analyses, boundary conditions of the rabbit femur were simulated and analyses were performed with respect to different loading scenarios. Calculations of equivalent stress distributions within the cements were applied, with a completely bonded cement surface for the bioactive cement and with a continuously interfering fibrous tissue layer for the reference cement. The bioactive cement revealed good in vivo bioactivity. In the bioactive cement group two failures (33?%), with complete break-out of the prosthesis occurred, while none in the reference group. Finite element analyses of simulated bioactive cement fixation showed an increase in maximal equivalent stress by 49.2 to 109.4?% compared to the simulation of reference cement. The two failures as well as an increase in calculated equivalent stress highlight the importance of fatigue properties of polymethylmethacrylate in general and especially when developing bioactive cements designated for load-bearing conditions.     

A novel sheep vertebral bone defect model for injectable bioactive vertebral augmentation materials

New injectable bone substitutes have been developed that are, unlike polymethylmethacrylate, biologically active and have an osteogenic effect leading to osteogenesis and bone remodeling for vertebroplasty or kyphoplasty. In this study, we developed a sheep vertebral bone defect model to evaluate the new bioactive materials and assessed the feasibility of the model in vivo. Bone voids were experimentally created on lumbar vertebrae L2–L5 with L1 and L6 left intact as a normal control in mature sheep. The defect vertebrae L2–L5 in each sheep were randomized to receive augmentation with calcium phosphate cement (CPC) or sham. Vertebrae (L1–L6) were collected after 2 and 24 weeks of the cement augmentation and their strength and stiffness, as well as osseointegration activity and biodegradability, were evaluated. Finally, CPC significantly improved the strength and stiffness of vertebrae but did not yet restore it to the normal level at 24 weeks. Osteogenesis occurred at a substantially high level after 24 weeks of CPC augmentation or sham. Therefore, the sheep vertebral model with one void, 6.0 mm in diameter and 15.0 mm in depth, is replicable and can be used for evaluating the new injectable bioactive materials in vertebral augmentation or reconstruction.     

Bactericidal strontium-releasing injectable bone cements based on bioactive glasses

Strontium-releasing injectable bone cements may have the potential to prevent implant-related infections through the bactericidal action of strontium, while enhancing bone formation in patients suffering from osteoporosis. A melt-derived bioactive glass (BG) series (SiO₂–CaO–CaF₂–MgO) with 0–50% of calcium substituted with strontium on a molar base were produced. By mixing glass powder, poly(acrylic acid) and water, cements were obtained which can be delivered by injection and set in situ, giving compressive strength of up to 35 MPa. Strontium release was dependent on BG composition with increasing strontium substitution resulting in higher concentrations in the medium. Bactericidal effects were tested on Staphylococcus aureus and Streptococcus faecalis; cell counts were reduced by up to three orders of magnitude over 6 days. Results show that bactericidal action can be increased through BG strontium substitution, allowing for the design of novel antimicrobial and bone enhancing cements for use in vertebroplasty or kyphoplasty for treating osteoporosis-related vertebral compression fractures.     

Comparison of the material properties of PMMA and glass-ionomer based cements for use in orthopaedic surgery

The intrisic benefits of low exotherm and bioactivity have generated interest in utilizing glass-ionomer cements (GIC) as a bone cement replacement in orthopaedic surgery. This paper is concerned with evaluating the mechanical properties of compressive strength, flexural strength, and fracture toughness for two traditional GICs, one resin-modified GIC (an experimental bone cement) and two polymethylmethacrylate (PMMA) cement systems. To determine the suitability of a GIC system for use in the clinical orthopaedic setting, the additional characteristics of setting exotherm and setting time have also been evaluated. The characterization of these two vastly different cement systems has raised some concern as to the applicability of using the current orthopaedic standards for the testing of GIC systems. In particular, issues relating to the strain rate dependence of PMMA cement and the exothermic basis for determining setting time are not applicable as these factors are not characteristic of GIC systems. Whilst the intrinsic benfits of current GIC systems are well understood and generally accepted, this study has shown their intrinsic mechanical properties to be inferior to current PMMA cements. Improvement in the mechanical properties of traditional GICs have been achieved with the addition of a resin component (HEMA). © 2001 Kluwer Academic Publishers     

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 °C for Palacos R® and 41 °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.     

Biological response of new activated acrylic bone cements with antiseptic properties. Histomorphometric analysis

The biological response to an acrylic bone cement cured with 4,4′-bis-dimethylamino benzydrol (BZN) as activator of reduced cytotoxicity and antiseptic properties, has been carried out and compared with that obtained for CMW 3 cement. Histomorphometrical data (undecalcified trichromic Goldner staining) were obtained by measuring the most significant variables at the bone-cement interface. Quantitative results of tissue response revealed that newly formed bone and connective tissue were maximum at 4 weeks whereas bone marrow increased with time of implantation for both cements. Statistical analysis (p < 0.05) showed no significant differences in newly formed bone and bone marrow with time and between both groups, however, connective tissue significantly decreased between 4 weeks and 12 weeks for BZN cement, and between 12 weeks and 24 weeks for CMW3. By comparing both cements at each time, lower significant percentage of connective tissue at the bone-cement interface of the BZN cement, was obtained at 12 and 24 weeks, however, a very low amount of connective tissue was found for both cements. All the results indicate that the new activated system could be applied clinically in a relatively short time, after the corresponding preclinical study.     

New radiopaque acrylic bone cement. II. Acrylic bone cement with bromine-containing monomer

Bromine-containing methacrylate, 2-(2-bromopropionyloxy) ethyl methacrylate (BPEM), had been used in the formulation of acrylic radiopaque cements. The effect of this monomer incorporated into the liquid phase of acrylic bone cement, on the curing parameters, thermal properties, water absorption, density, compression tests and radiopacity was studied. A decrease of maximum temperature and an increase of the setting time were observed with the addition of the bromine-containing monomer in the radiolucent cement composition. Adding BPEM in radiolucent acrylic bone cements composition results in the decrease of glass transition temperature and increase of its thermal stability. Acrylic bone cements modified with bromine-containing comonomer are characterized by polymerization shrinkage lower than the radiolucent cement. Addition of bromine-containing comonomer in radiolucent acrylic bone cement composition determines the increase of compressive strength. Acrylic bone cements modified with bromine-containing comonomer proved to be radiopaque.     

A preliminary study of the release of quaternary ammonium antimicrobial compounds from acrylic bone cement

The quaternary ammonium compounds benzalkonium chloride and cetyl pyridinium chloride have been studied as potential anti-microbial additives for incorporation into acrylic bone cement. Using the commercial bone cement Palacos K-40, each compound was added at 1% and 5% by mass. Setting time of the cement was 9.75 min. This did not change when benzalkonium chloride (5%) was present, but was shortened to 9.00 min by 5% cetyl pyridinium chloride. Release of additive was estimated by determining chloride release from set cement specimens using a chloride-ion selective electrode. This showed that release occurred but was a complicated process and did not follow simple diffusion-based kinetics. Release thus appeared to occur by a similar overall mechanism to that of gentamicin sulphate from bone cements. The results show that these anti-microbial compounds can be incorporated into acrylic bone cement and then released in a satisfactory manner and suggest that these compounds have the potential to replace gentamicin sulphate as active ingredients in orthopaedic cements.     

Acceleration of calcium phosphate formation on bioactive PMMA-based bone cement by controlling spatial design

Polymethylmethacrylate (PMMA)-based bone cement is widely used for the fixation of artificial joints. However, it is not considered a bioactive material because it lacks the ability to induce a direct bond with bone. In order to improve the long-term stability of cemented fixations, the development of bioactive bone cements is desirable. An essential requirement of a bioactive material includes the induction of bone-like apatite on its surface within the in vivo environment. Previously, we prepared bioactive PMMA-based bone cements by a modification with water-soluble calcium salts and alkoxysilane. Because spatial design may enhance apatite formation on bioactive material surfaces in vivo, we aimed to evaluate the effect of spatial design on apatite formation on modified PMMA-based bone cements in simulated body fluid (SBF). We found that an appropriate spatial design shortened the induction period for the apatite deposition on the modified bone cements. It is expected that osteoconduction would be enhanced in spontaneously created gap between the cement and the host bone leading to tight integration.     

A novel acrylic copolymer for a poly(alkenoate) glass-ionomer cement

The interest in the clinical use of polyalkenoate cements stems mainly from their behavior as bioactive adhesive materials with therapeutic action. Glass-ionomer cements set by an acid-base reaction between a degradable glass and a poly(alkenoic acid) and the therapeutic action is related to the release of fluoride ions which are present in the hardened cement that show a sustained release over years, responsible for caries inhibition in teeth. Conventional glass-ionomers, however, suffer from some disadvantages such as short working time, initial moisture sensitivity and prone to desiccation after setting and are generally brittle. In the present study, a poly(alkenoic acid) copolymer was synthesized based on acrylic acid and 2-hydroxyethylmethacrylate (HEMA) using azobisisobutyronitrile as the initiator and characterized. The acid–base reaction was carried out by reacting aqueous solutions of the new copolymer (40 and 60%) with a commercial aluminofluorosilicate glasses as used in conventional glass-ionomer cements. The results showed that the copolymer of HEMA and acrylic acid was a viable poly(alkenoic) acid for formation of glass-ionomer cements.     

Injectability evaluation of tricalcium phosphate bone cement

Calcium phosphate cements are biomaterials made from a mixture of calcium phosphate powder in aqueous solutions that forms a paste that reacts at the body temperature and hardens as a result of precipitation reactions. These cements are commonly used in dentistry and orthopedic bone filling surgeries, which require extremely invasive procedures. The challenge consists in formulating an injectable paste by additives incorporation. In this work, three different additives (carboxymethylcellulose, agar polymer and sodium alginate) were incorporated to tricalcium phosphate, in concentrations of 0.4, 0.8, 1.6, 3.2 and 6.4 wt.%. Injectability was evaluated through a new method developed for this purpose. Results showed that it was possible to obtain injectable compositions of α-tricalcium phosphate cement. It was verified that the injectability depends on the rheological behavior of the pastes and injection time. In this study, pastes with viscosity suitable for good homogenization and injection were obtained.     

Bone cements and fillers: A review

Charnley [1] developed the first bone cement in the 1960s using poly(methyl methacrylate) (PMMA), which remains the most widely used material for fixation of orthopaedic joint replacements. In the field of dentistry, zinc polycarboxylate and glass polyalkenoate cements received major research interest from the 1970s to the present day. The discovery of a well-integrated intermediate layer between bone and many bioactive ceramic phases from the calcium–phosphate system, such as hydroxyapatite (HA), resulted in the development of new cements incorporating such phases. These investigations ranged from the development of castable bioactive materials to modified bioactive composites. This paper attempts to give a broad overview of the many different types of cements that have being developed in the past and those which are being researched at the present time. It has lead to a set of fundamental design criteria that should be considered prior to the development of a cement for use as a bone cement or in applications requiring a bone substitute.     

Influence of multiwall carbon nanotube functionality and loading on mechanical properties of PMMA/MWCNT bone cements

Poly (methyl methacrylate) (PMMA) bone cement—multi walled carbon nanotube (MWCNT) nanocomposites with weight loadings ranging from 0.1 to 1.0 wt% were prepared. The MWCNTs investigated were unfunctionalised, carboxyl and amine functionalised MWCNTs. Mechanical properties of the resultant nanocomposite cements were characterised as per international standards for acrylic resin cements. These mechanical properties were influenced by the type and wt% loading of MWCNT used. The morphology and degree of dispersion of the MWCNTs in the PMMA matrix at different length scales were examined using field emission scanning electron microscopy. Improvements in mechanical properties were attributed to the MWCNTs arresting/retarding crack propagation through the cement by providing a bridging effect and hindering crack propagation. MWCNTs agglomerations were evident within the cement microstructure, the degree of these agglomerations was dependent on the weight fraction and functionality of MWCNTs incorporated into the cement.