Composite Bone Cement Research Articles

Modification of acrylic bone cements by poly(ethylene glycol) with different molecular weight

The high polymerization temperature of acrylic bone cements can cause arthroplasty failure because of the thermal necrosis of surrounding bone tissue. To reduce this undesired effect we have developed novel acrylic bone cement composites containing a phase change material (PCM). As PCM poly(ethylene glycol) (PEG) of different molecular weight was applied and the effect of its incorporation on curing parameters, mechanical and morphological properties of acrylic bone cement was investigated. A significant decrease in maximum temperature from 65.8°C to 47.4°C and slight increase of setting time were observed. PEG introduction also contributed to the thermal stability of acrylic bone cement increase. SEM investigation of modified bone cement confirmed that the microstructure does not alter considerably because of PEG content. It was found that both PEG addition and incubation test contribute to an inconsiderable decrease in mechanical strength of bone cement. However, the mechanical strength increase can be caused by the fresh bone tissue incorporation into the pores appearing in bone cement. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of the biphasic calcium composite (BCC), a novel bone cement, in a minipig model of pulmonary embolism

Polymethylmethacrylate (PMMA) bone cement, which is used as a filler material in vertebroplasty, is one of the major sources of pulmonary embolism in patients who have undergone vertebroplasty. In the present study, we established and evaluated two animal models of pulmonary embolism by injecting PMMA or biphasic calcium composite (BCC) bone cement with a negative surface charge. A total of 12 adults and healthy Wuzhishan minipigs were randomly divided into two groups, the PMMA and BBC groups, which received injection of PMMA bone cement and BBC bone cement with a negative surface charge in the circulation system through the pulmonary trunk, respectively, to construct animal models of pulmonary embolism. The hemodynamics, arterial blood gas, and plasma coagulation were compared between these two groups. In addition, morphological changes of the lung were examined using three-dimensional computed tomography. The results showed that both PMMA and BCC injections induced pulmonary embolisms in minipigs. Compared to the PMMA group, the BCC group exhibited significantly lower levels of arterial pressure, pulmonary artery pressure, blood oxygen pressure, blood carbon dioxide pressure, blood bicarbonate, base excess, antithrombin III and D-dimer. In conclusion, BCC bone cement with a negative surface charge is a promising filler material for vertebroplasty.

Remodeling of an injectable, settable, and cell-degradable composite bone cement with bone-like strength in a rabbit femoral plug defect model

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Morphological and mechanical characterization of composite bone cement containing polymethylmethacrylate matrix functionalized with trimethoxysilyl and bioactive glass

Medical polymers of biostable nature (e.g. polymethylmetacrylate, PMMA) are widely used in various clinical applications. In this study, novel PMMA-based composite bone cement was prepared. Bioactive glass (BAG) particulate filler (30wt%) was added to enhance potentially the integration of bone to the cement. The polymer matrix was functionalized with trimethoxysilyl to achieve an interfacial bond between the matrix and the fillers of BAG. The amount of trimethoxysilyl in the monomer system varied from 0 to 75wt%. The effects of dry and wet (simulated body fluid, SBF at +37°C for 5 weeks) conditions were investigated. In total, 20 groups of specimens were prepared. The specimens were subjected to a destructive mechanical test in compression. Scanning electron microscopy (SEM) and micro-computed tomography (micro-CT) were used to study the surface and the three-dimensional morphology of the specimens. The results of the study indicated that the addition of trimethoxysilyl groups led to the formation of a hybrid polymer matrix which, in lower amounts (<10wt% of total weight), did not significantly affect the compression properties. However, when the specimens stored in dry and wet conditions were compared, the water sorption increased the compression strength (~5–10MPa per test group). At the same time, the water sorption also caused an evident porous structure formation for the specimens containing BAG and siloxane formation in the hybrid polymer matrix.

Antibacterial and bioactive composite bone cements containing surface silver-doped glass particles

A bioactive silica-based glass powder (SBA2) was doped with silver (Ag+) ions by means of an ion-exchange process. Scanning electron microscopy (SEM), energy dispersion spectrometry (EDS) and x-ray diffraction (XRD) evidenced that the glass powder was enriched with Ag+ ions. However, a small amount of Ag2CO3 precipitated with increased Ag concentrations in the exchange solution. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of Ag-SBA2 towards Staphylococcus aureus were also evaluated and were respectively 0.05 mg ml−1 and 0.2 mg ml−1. Subsequently, Ag-SBA2 glass was used as filler (30%wt) in a commercial formulation of bone cement (Simplex™ P) in order to impart both antibacterial and bioactive properties. The composite bone cement was investigated in terms of morphology (using SEM) and composition (using EDS); the glass powder was well dispersed and exposed on the cement surface. Bioactivity tests in simulated body fluid (SBF) evidenced the precipitation of hydroxyapatite on sample surfaces. Composite cement demonstrated antibacterial properties and a compressive strength comparable to the commercial formulation.

Porous calcium phosphate-poly (lactic-co-glycolic) acid composite bone cement: A viable tunable drug delivery system

Calcium phosphate based cements (CPCs) are frequently used as bone void fillers for non-load bearing segmental bone defects due to their clinically relevant handling characteristics and ability to promote natural bone growth. Macroporous CPC scaffolds with interconnected pores are preferred for their ability to degrade faster and enable accelerated bone regeneration. Herein, a composite CPC scaffold is developed using newly developed resorbable calcium phosphate cement (ReCaPP) formulation containing degradable microspheres of bio-compatible poly (lactic-co-glycolic acid) (PLGA) serving as porogen. The present study is aimed at characterizing the effect of in-vitro degradation of PLGA microspheres on the physical, chemical and structural characteristics of the composite cements. The porosity measurements results reveal the formation of highly interconnected macroporous scaffolds after degradation of PLGA microspheres. The in-vitro characterizations also suggest that the degradation by products of PLGA reduces the pH of the local environment thereby increasing the dissolution rate of the cement. In addition, the in-vitro vancomycin release from the composite CPC scaffold suggests that the drug association with the composite scaffolds can be tuned to achieve control release kinetics. Further, the study demonstrates control release lasting for longer than 10weeks from the composite cements in which vancomycin is encapsulated in PLGA microspheres.

Two novel high performing composite PMMA-CaP cements for vertebroplasty: An ex vivo animal study

There is a growing body of the literature on new cement formulations that address the shortcomings of PMMA bone cements approved for use in vertebroplasty (VP) and balloon kyphoplasty (BKP). The present study is a contribution to these efforts by further characterization of two pre-mixed CaP filler-reinforced PMMA bone cements intended for VP; namely, PMMA-HA and PMMA-brushite cements. Each of these cements showed acceptable levels of various properties determined in porcine vertebral bodies. These properties included radiographic contrast, maximum exotherm temperature setting time, cement extravasation, stiffness change after fatigue loading, change of VB height after fracture following fatigue loading, and interdigitation. Each property value was comparable to or better than that for a PMMA bone cement approved for use in BKP. Thus, the results for the composite bone cements are promising.

A Novel Composite PMMA-based Bone Cement with Reduced Potential for Thermal Necrosis.

Percutaneous vertebroplasty (VP) and balloon kyphoplasty (BKP) are now widely used to treat patients who suffer painful vertebral compression fractures. In each of these treatments, a bone cement paste is injected into the fractured vertebral body/bodies, and the cement of choice is a poly(methyl methacrylate) (PMMA) bone cement. One drawback of this cement is the very high exothermic temperature, which, it has been suggested, causes thermal necrosis of surrounding tissue. In the present work, we prepared novel composite PMMA bone cement where microcapsules containing a phase change material (paraffin) (PCMc) were mixed with the powder of the cement. A PCM absorbs generated heat and, as such, its presence in the cement may lead to reduction in thermal necrosis. We determined a number of properties of the composite cement. Compared to the values for a control cement (a commercially available PMMA cement used in VP and BKP), each composite cement was found to have significantly lower maximum exothermic temperature, increased setting time, significantly lower compressive strength, significantly lower compressive modulus, comparable biocompatibility, and significantly smaller thermal necrosis zone. Composite cement containing 20% PCMc may be suitable for use in VP and BKP and thus deserves further evaluation.

Novel doped calcium phosphate-PMMA bone cement composites as levofloxacin delivery systems

Antibiotic-loaded acrylic bone cements (ALABCs) are well-established and cost-effective materials to control the occurrence of bone and joint infections. However, the inexistence of alternative antibiotics other than those already commercially available and the poor ability to bind to bone tissue hampering its biological function are still major drawbacks of ALABCs clinical application. The concept of this research work is to develop a novel bone cement (BC) drug delivery system composed by Mg- and Sr-doped calcium phosphate (CaP) particles as drug carriers loaded into a lactose-modified acrylic BC, which, to the best of our knowledge, has never been reported. CaP particles are known to promote bone ingrowth and current research is focused on using these carriers as antibiotic delivery systems for the treatment of bone infections, like osteomyelitis. Levofloxacin is a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues and increasingly being recommended to manage bone-related infections. Also, the lactose-modified BC matrix, with a more porous structure, has already proved to enhance antibiotic release from the BC inner matrix. This novel BC composite biomaterial has shown improved mechanical integrity, biocompatibility maintenance, and sustained release of levofloxacin, with concentrations over the minimum inhibitory concentration values after a 48h while maintaining antibacterial activity over an 8-week period against Staphyloccocus aureus and Staphyloccocus epidermidis, common pathogens associated with bone infections.

Effect of modification degree of nanohydroxyapatite on biocompatibility and mechanical property of injectable poly(methyl methacrylate)-based bone cement.

The objective of this study is to prepare a biocompatible nanohydroxyapatite/poly(methyl methacrylate) (HA/PMMA) composite bone cement, which has good mechanical property and can be used for vertebroplasty. Up to 40 wt % of nanohydroxyapatite (nano-HA) in the power, which was surface modified with poly(methylmethacrylate-co-γ-methacryloxypropyl timethoxysilane) [P(MMA-co-MPS)] copolymer, was incorporated into the composite bone cement. The content of P(MMA-co-MPS) on the surface of nano-HA (18.7%, 22.8%, and 26%) was determined through thermogravimetric analysis (TGA). The morphology of biomineralized surface of composite bone cement was observed under scanning electron microscope (SEM). The mechanical measurements of the composite cements implied that the interfacial interaction between the HA and PMMA matrix may be greatly enhanced after surface modification of HA. Biochemical assays indicated that the HA/PMMA bone cement had no cytotoxicity and induced no hemolysis. The cell adhesion and alkaline phosphatase (ALP) activity assays indicated that the biocompatibility of HA/PMMA bone cement could be promoted, demonstrating that it can be used as an ideal weight-bearing bone repair materials on clinical application.

Preparation and mechanical properties of reinforced hydroxyapatite bone cement with nano-ZrO2

In the research described, a new method was investigated to prepare hydroxyapatite (HAp) bone cement using nano-hydroxyapatite, CaO and (NH4)2HPO4 as initial raw materials, and reinforcement effects of HAp bone cement with ZrO2 nanotubes and ZrO2 nanoparticles were studied in detail. The morphologies, crystal structure and mechanical properties etc. were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffractometer (XRD), and electro-mechanical universal testing machine. Results indicated that after solidification the composition of bone cement was hydroxyapatite with good crystallinity and purity. Addition of ZrO2 nanoparticles or ZrO2 nanotubes to the bone cement could substantially improve its strength, the optimum addition amount being 20wt%, however, the enhancement effects between ZrO2 nanoparticles and ZrO2 nanotubes were slightly different.

Novel tricalcium silicate/magnesium phosphate composite bone cement having high compressive strength, in vitro bioactivity and cytocompatibility.

Although inorganic bone cements such as calcium phosphate cements have been widely applied in orthopaedic and dental fields because of their self-setting ability, development of high-strength bone cement with bioactivity and biodegradability remains a major challenge. Therefore, the purpose of this study is to prepare a tricalcium silicate/magnesium phosphate (C3S/MPC) composite bone cement, which is intended to combine the excellent bioactivity of C3S with remarkable self-setting properties and mechanical strength of MPC. The self-setting and mechanical properties, in vitro induction of apatite formation and degradation behaviour, and cytocompatibility of the composite cements were investigated. Our results showed that the C3S/MPC composite cement with an optimal composition had compressive strength up to 87 MPa, which was significantly higher than C3S (25 MPa) and MPC (64 MPa). The setting time could be adjusted between 3 min and 29 min with the variation of compositions. The hydraulic reaction products of the C3S/MPC composite cement were composed of calcium silicate hydrate (CSH) derived from the hydration of C3S and gel-like amorphous substance. The C3S/MPC composite cements could induce apatite mineralization on its surface in SBF solution and degraded gradually in Tris-HCl solution. Besides, the composite cements showed good cytocompatibility and stimulatory effect on the proliferation of MC3T3-E1 osteoblast cells. Our results indicated that the C3S/MPC composite bone cement might be a new promising high-strength inorganic bioactive material which may hold the potential for bone repair in load-bearing site.

Composite bone cements loaded with a bioactive and ferrimagnetic glass-ceramic: Leaching, bioactivity and cytocompatibility.

In this work, composite bone cements, based on a commercial polymethylmethacrylate matrix (Palamed®) loaded with ferrimagnetic bioactive glass-ceramic particles (SC45), were produced and characterized in vitro. The ferrimagnetic bioactive glass-ceramic belongs to the system SiO2-Na2O-CaO-P2O5-FeO-Fe2O3 and contains magnetite (Fe3O4) crystals into a residual amorphous bioactive phase. Three different formulations (containing 10, 15 and 20 wt.% of glass-ceramic particles respectively) have been investigated. These materials are intended to be applied as bone fillers for the hyperthermic treatment of bone tumors. The morphological, compositional, calorimetric and mechanical properties of each formulation have been already discussed in a previous paper. The in vitro properties of the composite bone cements described in the present paper are related to iron ion leaching test (by graphite furnace atomic absorption spectrometer), bioactivity (i.e. the ability to stimulate the formation of a hydroxyapatite - HAp - layer on their surface after soaking in simulated body fluid SBF) and cytocompatibility toward human osteosarcoma cells (ATCC CRL-1427, Mg63). Morphological and chemical characterizations by scanning electron microscopy and energy dispersion spectrometry have been performed on the composite samples after each test. The iron release was negligible and all the tested samples showed the growth of HAp on their surface after 28 days of immersion in a simulated body fluid (SBF). Cells showed good viability, morphology, adhesion, density and the ability to develop bridge-like structures on all investigated samples. A synergistic effect between bioactivity and cell mineralization was also evidenced.

In situ Synchrotron X-ray Powder Diffraction Study of the Early Hydration of α-tricalcium Phosphate/tricalcium Silicate Composite Bone Cement

Bioactivity, osteogenicity and mechanical properties of α-tricalcium phosphate (α-TCP) based phosphates cements can be improved by adding tricalcium silicate (C3S); however, the addition of C3S delays the precipitation and growth of calcium deficient hydroxyapatite (CDHA). Thus, the aim of this work was the study of in situ setting reaction of α-TCP/C3S composite bone cement under high energy X-ray generated by a synchrotron source within the first 72h. The results showed that the addition of C3S induces the precipitation of nanosized CDHA at early times depending on the added content. Calculated crystallite sizes showed that the higher the content of C3S, the smaller the crystal size at the beginning of the precipitation. These results are different from those obtained by conventional XRD method, suggesting that the proposed technique is a powerful tool in determining the composition and extent of reaction of CPCs surfaces in real time.

Preparation of calcium phosphate cement and polymethyl methacrylate for biological composite bone cements.

BackgroundWe studied the biological safety, biomechanics, and tissue compatibility of calcium phosphate cement and Polymethyl Methacrylate composite bone cement mixed in different ratios.Material/MethodsCPC and PMMA were mixed in different ratios (3: 1, 2: 1, 1: 1, 1: 2, 1: 5, 1: 10, 1: 15, and 1: 20). PMMA solvent is a general solvent containing a dissolved preparation of the composite bone cement specific to a given specimen to determine biological safety, biomechanics, and tissue compatibility.ResultsThe CPC/PMMA (33%) group, CPC/PMMA (50%) group, CPC/PMMA (67%) group, and CPC/PMMA (75%) group were more in line with the composite bone cement without cytotoxicity requirements. The compressive strength of the CPC/PMMA (67%) group and CPC/PMMA (75%) group was 20Mpa–30Mpa, while that of the CPC/PMMA (4.8%) group, CPC/PMMA (6.25%) group, CPC/PMMA (9.1%) group, CPC/PMMA (16.7%) group, CPC/PMMA (33%) group, and CPC/PMMA (50%) group was 40Mpa–70Mpa. Curing time was longer in the CPC group (more than 11 min) and shorter in the PMMA group (less than 2 min). The results of weight loss rate showed that there were no significant differences between the CPC/PMMA group (4.8%, 6.25%, 9.1%, 16.7%, 33%) and PMMA control group (p>0.05). With the decrease of CPC content, the rate of weight loss gradually decreased.ConclusionsThe CPC/PMMA (50%) group, CPC/PMMA (67%) group, and CPC/PMMA (75%) group provide greater variability and selectivity for the composite bone cement in obtaining better application.

Silicate bioceramic/PMMA composite bone cement with distinctive physicochemical and bioactive properties

New bioactive silicate/PMMA composite bone cements possess improved setting properties, high mechanical strength, excellent apatite-mineralization ability and biological activity for injectable bone regeneration materials application.

Effects of Alendronate Sodium Content on the Interface Strengths of Composite Acrylic Bone Cement.

Objective. Aim to study how the content of alendronate affected shear strengths at bone-bone cement-metal interfaces. Methods. All samples were divided into 6 groups, G0–G5. On the 1st and 60th day after surgery, bone-bone cement interface shear strengths and bone densities were examined. Interface strengths of metal-bone cement specimens were studied before immersion and 4 weeks after immersion. Results. On the 60th day, bone-bone cement interface shear strengths and bone densities showed significant differences (P < 0.05), and compared with G0, G2–G5 values increased significantly (P < 0.05), and the peak value was met in G3. Compared with the 1st day, on the 60th postoperative day both factors decreased significantly in G0 and G1 (P < 0.05). Four weeks after immersion, with the increasing dose of alendronate, the shear strengths decreased gradually and in G5 decreased significantly (P < 0.05). Compared with before immersion, the metal-bone cement interface strengths decreased significantly 4 weeks after immersion (P < 0.05). Conclusions. 50–500 mg alendronate in 50 g cement powders could prevent the decrease of shear strengths at bone-bone cement interfaces and had no effect on metal-bone cement interface strengths. While the addition dose was 100 mg, bone cement showed the best strengths.

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

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

Bone cement based on vancomycin loaded mesoporous silica nanoparticle and calcium sulfate composites.

A novel bone cement pellet, with sustained release of vancomycin (VAN), was prepared by mixing VAN loaded mesoporous silica nanoparticle (MSN) and calcium sulfate α-hemihydrate (CS) together. To improve the VAN loading ability, MSN was functionalized with aminopropyltriethoxysilane (APS) to give APS-MSN. The VAN loading content and entrapment efficiency of APS-MSN could reach up to 45.91±0.81% and 84.88±1.52%, respectively, much higher than those of MSN, which were only 3.91% and 4.07%, respectively. The nitrogen adsorption-desorption measurement results demonstrated that most of the VAN were in the pores of APS-MSN. The CS/VAN@APS-MSN composite pellet showed a strongly drug sustained release effect in comparison with CS control pellet. The in vitro cell assays demonstrated that CS/APS-MSN composite was highly biocompatible and suitable to use as bone cement. Furthermore, CS/VAN@APS-MSN pellet showed no pyrogenic effect and meet the clinical requirements on hemolytic reaction. These results imply that CS/VAN@APS-MSN was an ideal candidate to replace CS bone cement in the treatment of open fractures.

A novel controlled-release system for antibacterial enzyme lysostaphin delivery using hydroxyapatite/chitosan composite bone cement.

In this work, a lysostaphin-loaded, control-released, self-setting and injectable porous bone cement with efficient protein delivery was prepared by a novel setting method using hydroxyapatite/chitosan (HA/CS) composite scaffold. The cement samples were made through cementitious reactions by mixing solid powder, a mixture of HA/CS composite particles, lysostaphin, Ca(OH)2, CaCO3 and NaHCO3, with setting liquid containing citric acid, acetic acid, NaH2PO4, CaCl2 and poloxamer. The setting parameters of the cement samples were determined. The results showed that the final setting time was 96.6±5.2 min and the pH value increased from approximately 6.2 to nearly 10 during the setting process and the porosity was 34% at the end. And the microstructure and composition were detected by scanning electron microscopy (SEM), x-ray diffraction and Fourier transform-infrared spectroscopy. For the release behavior of lysostaphin loaded in the cement sample, the in vitro cement extract experiment indicated that about 94.2±10.9% of the loaded protein was released before day 8 and the in vivo Qdot 625 fluorescence tracking experiment showed that the loaded protein released slower than the free one. Then the biocompatibility of the cement samples was evaluated using the methylthiazol tetrazolium assay, SEM and hematoxylin-eosin staining, which suggested good biocompatibility of cement samples with MC 3T3-E1 cells and subcutaneous tissues of mice. Finally the antibacterial activity assay indicated that the loaded lysostaphin had good release ability and strong antibacterial enzymatic activity against methicillin-resistant Staphylococcus aureus. Collectively, all the results suggested that the lysostaphin-loaded self-setting injectable porous bone cement released the protein in a controlled and effective way and the protein activity was well retained during the setting and releasing process. Thus this bone cement can be potentially applied as a combination of artificial bone substitute and controlled-release system for delivery of lysostaphin to treat bone defects and infections.