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In vitro cytokine production by mononuclear cells exposed to bone cement extracts.

The authors evaluated the ability of bone cement to modify the profile of pro-inflammatory cytokines secreted by the immune cells. Peripheral blood mononuclear cells (PBMC) collected from healthy individuals were cultured with cement extracts and tested to assess the release of IL-1beta, TNFalpha, GM-CSF and IL-6 in both unstimulated and PHA-stimulated PBMC. The cytokine release of unstimulated PBMC was very poor, and in particular the IL-1beta was undetectable: the addition of cement extract increased both TNFalpha and GM-CSF release and decreased IL-6, sometimes significantly. The most recurrent observation in PHA-stimulated PBMCs exposed to bone cement extract was the increase in both IL-1beta and IL-6 release, while both the mean concentration and the index of release of TNFalpha and GM-CSF were changeable. In conclusion our results showed that leachable components of some bone cements can induce in vitro the release of pro-inflammatory cytokines which are known to be involved in the bone resorption associated with aseptic loosening of hip prostheses. These findings allowed us to identify materials endowed with the highest inflammatory power.

Biocompatible Materials↗

[Physical properties of apatite bone cement].

Some properties of the apatite bone cement which is composed of alpha-tricalcium phosphate and hydroxyapatite for use as a biomaterial were investigated. The powder of cement was synthesized from calcium phosphate, calcium carbonate and dicalcium phosphate by solid reaction. Several kinds of citric acid solutions were used for hardening. When the liquid for hardening was 30% (w/w) citric acid solution, the setting time was about six minutes, the compressive strength of hardened bodies was 24.96 MPa, and the solubility was about 1.4 wt%. The compressive strength was increased by the addition of Na or K salt. Especially, when copolymer of acrylic acid/itaconic acid was added to the liquied, the strength was increased about three times, but the setting time was significantly shortened. The results of this study indicate that the apatite bone cement is a potentially highly useful biomaterial for dental and medical applications.

Apatites↗

[Experimental observations on acrylic bone cement containing antitumor drugs].

By methods of human osteosarcoma cell culture in vitro, 3H-TdR isotope incorporation, gas chromatography and animal test, experimental observations were made on acrylic bone cement containing antitumor drugs. The results were as follows: 1. BLMA5, DACT, Ara-c, CDDP, and ADM were more thermostable. It is possible that these drugs can endure the polymerizing heat of bone cement. 2. The effective release of BLMA5, Ara-c and DACT from bone cement persisted over 2 months. 3. Scanning electron microscopy revealed that drug particles in the bone cement decreased or disappeared after immersion of the cement in tissue culture medium or implantation of it in animal bones. This shows that drug particles can be released from bone cement in vitro or in vivo 4. Animal experimental demonstrated that the bone cement containing BLMA5 or Ara-c had no effect on the healing of soft tissue, and the injury in local bone and bone marrow adjacent to the bone cement was slight and could recover in 4-8 weeks. 5. The release of residual monomer from polymerized bone cement continued as long as one month. Although the residual monomer inhibited the growth of tumor cells slightly during the early stage, it was far from being as effective as medicated bone cement.

Animals↗

Gentamicin release from modified acrylic bone cements with lactose and hydroxypropylmethylcellulose.

Modified polymethylmethacrylate (PMMA) bone cements formulations were prepared by including different proportions of gentamicin and release modulators such as lactose or hydroxypropylmethylcellulose (HPMC). Surface aspect, gentamicin release and porosity of these modified formulations were studied by means of scanning electron microscopy (SEM), a specially designed system for the dissolution studies of the bone cements, and mercury intrusion porosimetry. Lactose modified cements presented an irregular surface with numerous hollows and voids due to the lactose dissolution. HPMC cements presented a characteristic laminated and flaky surface. The drug release of lactose formulations was up to four-fold greater (13%) than the commercial bone cement CMW1 Gentamicin one (3%). The amount of gentamicin eluted at the first withdrawn sample ranged from 30% to 60% of total gentamicin released over the assay. Gentamicin release from lactose formulations increased as lactose percentage was increased which agree with the porosity results. Nevertheless, the use of release modulator HPMC increased porosity, but did not produce an increase in the gentamicin release. HPMC dissolution creates a surrounding sticky and viscous medium similar to a gel that makes the gentamicin release from the cement matrix difficult.

Anti-Bacterial Agents↗

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

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

Benzoyl Peroxide↗

Mechanical behaviour of a new acrylic radiopaque iodine-containing bone cement.

In total hip replacement, fixation of a prosthesis is in most cases obtained by the application of methacrylic bone cements. Most of the commercially available bone cements contain barium sulphate or zirconium dioxide as radiopacifier. As is shown in the literature, the presence of these inorganic particles can be unfavourable in terms of mechanical and biological properties. Here, we describe a new type of bone cement, where X-ray contrast is obtained via the introduction of an iodine-containing methacrylate copolymer; a copolymer of methylmethacrylate and 2-[4-iodobenzoyl]-oxo-ethylmethacrylate (4-IEMA) is added to the powder component of the cement. The properties of the new I-containing bone cement (I-cement) are compared to those of a commercially available bone cement, with barium sulphate as radiopacifier (B-cement). The composition of the I-cement is adjusted such that similar handling properties and radiopacity as for the commercial cement are obtained. In view of the mechanical properties, it can be stated that the intrinsic mechanical behaviour of the I-cement, as revealed from compression tests, is superior to that of B-cement. Concerning the fatigue behaviour it can be concluded that, though B-cement has a slightly higher fatigue crack propagation resistance than I-cement, the fatigue life of vacuum-mixed I-cement is significantly better than that of B-cement. This is explained by the presence of BaSO4 clumps in the commercial cement; these act as crack initiation sites. The mechanical properties (especially fatigue resistance) of the new I-cement warrant its further development toward clinical application.

Bone Cements↗

[Microangiographic and histologic findings in the tibiae of rats after implantation of bone cement (author's transl)].

The reaction of bone tissue to the filling of the medullary cavity with acrylic bone cement was studied in the rat by histological and microangiographic methods. Three months after plugging, the fibrous borderline tissue between cement and bone had changed into newly formed bone with a secondary medullary cavity, depending on the content of monomer next to the tissue. The blood support of the bone came from periosteal vessels. After 6 months a definitive secondary medullary cavity had been established, the cement was enveloped by newly formed primary bone, and the inner and middle portions of the cortical bone had been invaded by vessels originating from the secondary medullary cavity.

Angiography↗

Influence of oscillatory mixing on the injectability of three acrylic and two calcium-phosphate bone cements for vertebroplasty.

Injecting acrylic and, increasingly, calcium-phosphate cements into the porous bone structure is an emerging procedure, referred to as vertebroplasty, for the augmentation of osteoporotic vertebrae. Despite the benefits of vertebroplasty, it has limitations. The limitations of interest in this study are the injectability of bone cements and their mixing variability (i.e., low reproducibility of resulting viscosity). The objective of this study is to investigate the effect of oscillatory versus manual mixing on cement viscosity and mixing variability. Five cements are tested: (a) Vertebroplastic, (b) DP-Pour, (c) Antibiotic Simplex, (d) chronOS Inject, and (e) Biopex. Compared to manual mixing, oscillatory mixing significantly decreased the mean viscosity and the mixing variability, which was inferred from the coefficient of variation. For example, under oscillatory mixing, the viscosity and the variability for Vertebroplastic decreased to one-third of the corresponding values for manual mixing. Similar results were obtained for the other cements. The decrease in viscosity is attributed to the pseudo-plastic behavior of bone cements. The decrease in the variability of cement viscosity was attributed to greater dispersive mixing of the cement components under oscillatory mixing. The decrease in viscosity eases the injection by reducing the pressure required. The decrease in the variability of cement viscosity increases reproducibility of the cement injection. Oscillatory mixing appears to have the potential to contribute to improving vertebroplasty.

Bone Substitutes↗

Formation of a synovial-like membrane at the bone-cement interface. Its role in bone resorption and implant loosening after total hip replacement.

Histologic evaluation of tissue surrounding the loosened components after joint replacement reveals the presence of a synovial-like lining adjacent to the polymethyl methacrylate cement. The tissue is heavily infiltrated with particulate cement as well as polyethylene associated with a foreign body-type giant cell reaction. That this tissue response may be responsible for the bone lysis associated with loosening is suggested by the demonstration of high prostaglandin E2 levels and enhanced bone resorbing activity in the tissue culture medium of fragments from this membrane.

Arachidonic Acid↗

EPR study of free radicals in PMMA bone cement: a feasibility study.

In order to determine the feasibility of using electron paramagnetic resonance (EPR) to monitor the molecular processes occurring in polymethylmethacrylate (PMMA) bone cement, a preliminary study has been conducted on the bone cement in vitro. It has been found that a sufficient concentration of free radicals is generated in the bone cement during the polymerization process so that both the polymerization and the curing can be monitored by EPR. The results of these measurements on both radiolucent and radiopaque Surgical SimplexR P bone cement are presented. It has also been found that free radicals are present in the radiopaque bone cement powder as received from the manufacturer. These radicals which apparently are produced in the radiation sterilization process have been found to be unaffected by the polymerization/curing process and to be stable for temperatures below about 100 degrees C. It has clearly been shown that EPR can used to monitor the molecular processes of bone cement in vitro. It is hoped that this technique can be utilized to monitor the in vivo ageing process of bone cement used to fix orthopedic implants.

Bone Cements↗

Bioactive bone cement as a principal fixture for spinal burst fracture: an in vitro biomechanical and morphologic study.

STUDY DESIGN: An in vitro biomechanical and radiographic study to evaluate the properties of a newly developed bioactive bone cement for stabilization of the fractured spine, suitable for minimally invasive application. OBJECTIVES: To determine the mechanical stability of the fractured spine after injection of the newly developed bioactive bone cement under quasi-static and cyclic loading regimens. SUMMARY OF BACKGROUND DATA: Bone cement injection has been reported as a potentially useful, minimally invasive technique for treating vertebral body fracture or stabilizing osteoporosis. However, potential problems associated with the use of polymethylmethacrylate (PMMA) have prompted the search for alternative solutions. The use of bioactive bone cement as a potential replacement for PMMA has been reported. METHODS: Biomechanical and radiographic analyses were used to test the mechanical stability of the fractured spine. The cement used was formed from hydroxyapatite powder containing strontium and bisphenol A diglycidylether dimethacrylate (D-GMA) resin. Twenty-six fresh porcine spine specimens (T10-L1) were divided into three groups: pilot, intact, and cemented. Spinal stiffness and failure strength were recorded in the intact group with the specimens flexed at 10 degrees. Uniform injuries were created in all specimens of the cemented group, and compressive loading was applied with 10 degrees of flexion until a fracture occurred. The bone cement was injected into the fractured spine, and stiffness was evaluated after 1 hour. Failure strength was also recorded after 3000 and 20,000 fatigue load cycles. Morphology of the specimens was observed and evaluated. RESULTS: Results from a cell biocompatibility test indicated that the new bioactive bone cement was favorable for cell growth. Spinal stiffness significantly decreased after fracture (47.5% of intact condition). Instant stiffness of the spine recovered to 107.8% of the intact condition after bone cement injection. After 3000 and 20,000 cycles of fatigue loading, stiffness of the cemented spine was found to be 93.5% and 94.4% of intact stiffness, respectively (P < 0.05). Average failure strength of the spine was 5056 N (after 3000 cycles) and 5301 N (after 20,000 cycles) after bone cement injection and fatigue loading. Radiographs and cross-sectional observations indicated a good cement-bone bonding and fracture fill. CONCLUSIONS: A new bioactive bone cement without cytotoxic effect has been developed. Results show that minimally invasive techniques to apply this cement to porcine spines results in augmentation of mild burst fractures such that the original stiffness and strength of the vertebra are recovered. This new cement therefore shows potential as an augmentation to traditional instrumentation in the surgical management of vertebral fractures. The potential for further clinical applications is currently under investigation.

Animals↗

The effect of cross-linking agents on acrylic bone cements containing radiopacifiers.

Poly(methylmethacrylate) PMMA, based cements are the most widely used bone cements in joint replacement surgery. Although, there are some disadvantages in the use of these cements, the clinical success rate is fairly high. Intrinsic radiopacity is difficult to achieve in these cements due to the constituent elements of the PMMA polymer. As radiopacity is an essential requirement, PMMA bone cements have been rendered radiopaque by blending heavy metal ion salts, which tend to adversely affect the mechanical and biological properties of the bone cement. In this study, dimethacrylate cross-linking agents were added to the monomer phase in order to generate a cross-linked matrix, with barium sulphate as a radiopaque agent. The results suggest that the mechanical properties can be improved or retained with the addition of such cross-linking agents.

Acrylates↗

Static and fatigue mechanical behavior of bone cement with elevated barium sulfate content for treatment of vertebral compression fractures.

The use of bone cement to treat vertebral compression fractures in a percutaneous manner requires placement of the cement under fluoroscopic image guidance. To enhance visualization of the flow during injection and to monitor and prevent leakage beyond the confines of the vertebral body, the orthopedic community has described increasing the amount of radiopacifier in the bone cement. In this study, static tensile and compressive testing, as well as fully reversed fatigue testing, was performed on three PMMA-based bone cements. Cements tested were SimplexP with 10% barium sulfate (Stryker Orthopedics, Mahwah, NJ) which served as a control; SimplexP with 36% barium sulfate prepared according to the clinical recommendation of Theodorou et al.; and KyphX HV-R with 30% barium sulfate (Kyphon Inc., Sunnyvale, CA). Static tensile and compressive testing was performed in accordance with ASTM F451-99a. Fatigue testing was conducted in accordance with ASTM F2118-01a under fully reversed, +/-10-, +/-15-, and +/-20-MPa stress ranges. Survival analysis was performed using three-parameter Weibull modeling techniques. KyphX HV-R was found to have comparable static mechanical properties and significantly greater fatigue life than either of the two control materials evaluated in the present study. The static tensile and compressive strengths for all three PMMA-based bone cements were found to be an order of magnitude greater than the expected stress levels within a treated vertebral body. The static and fatigue testing data collected in this study indicate that bone cement can be designed with barium sulfate levels sufficiently high to permit fluoroscopic visualization while retaining the overall mechanical profile of a conventional bone cement under typical in vivo loading conditions.

Barium Sulfate↗

Carbon fiber-reinforced bone cement in orthopedic surgery.

A tougher, more fatigue-resistant bone cement consisting of short, highmodulus carbon fibers dispersed randomly in normal ply(methyl methacrylate) bone cement has been developed. Fatigue and impact tests are reported that demonstrate the superior fracture resistance and prolonged load-carrying ability of this system. The use of this carbon fiber-reinforced bone cement in the treatment of a pathological fracture of the femur associated with neoplastic disease of the bone is reported. The tougher cement has provided long-term stability of the fracture.

Bone Cements↗

[The biological fixation strength of the bone particle impregnated bone cement].

This article reports the result of the comparative study on the biological fixation strength of two kinds of bone particle impregnated bone cement. Organic and inorganic bone particle impregnated bone cement were implanted into alternative side of the upper femurs of New Zealand rabbits. The cancellous bone and cortical bone segments of the implanted femurs removed at intervals of 1, 2 and 3 months after operation were subjected to push-out test. In cancellous bone segment, shearing strength of cement-bone interface was increased gradually, but no significant difference between these two kinds of cement after 3 months operation. In cortical bone segment, the interface shearing strength was lower than that of the cancellous bone, but it increased rapidly from 1 month, especially for the organic bone particle bone cement, after 3 months operation the interface shearing strength had a significant difference between the two kinds of cement. More prominent biological fixation effect showed in the organic bone particle group.

Animals↗

Incudostapedial rebridging ossiculoplasty with bone cement.

OBJECTIVE: This study reports the authors' technique and hearing results with bone cement reconstruction of the incudostapedial chain. The technique is called incudostapedial rebridging ossiculoplasty. STUDY DESIGN: A retrospective analysis of the hearing results of the incudostapedial rebridging ossiculoplasty was performed on 15 patients. BACKGROUND: Recently, bone cements have been available commercially, and their use in otologic surgery is increasing. Polymaleinate glass ionomer cement is a commercially available bone cement that can be used to reconstruct a discontinuity between the incus and the stapes. SETTING: Tertiary referral center. PATIENTS: Disease-free or cleansed middle ear and mastoid and intact ossicular chain except for discontinuity between the long process of the incus and the head of the stapes. INTERVENTIONS: Therapeutic. MAIN OUTCOMES MEASURES: Functional results of incudostapedial rebridging ossiculoplasty. RESULTS: Of 15 patients, 9 achieved a successful hearing result (an air-bone gap within 20 dB) with incudostapedial rebridging ossiculoplasty after 1 year. The mean preoperative and postoperative air-bone gaps were 32.9 and 14.3 dB, respectively. CONCLUSIONS: Incudostapedial rebridging ossiculoplasty with bone cement is a cost-effective and safe procedure that yields good hearing results in selected patients.

Adolescent↗

Tissue response to in situ polymerization of a new two-solution bone cement: evaluation in a sheep model.

A two-solution bone cement (2-SC) was evaluated in a non-load bearing sheep model that simulated insertion of a cemented total joint replacement. A commercial powder-liquid bone cement formulation (Palacos R) was used as the control. The systemic response to the two cements was determined by monitoring changes in arterial blood pressure (ABP) and serum concentrations of methyl methacrylate monomer at intervals after insertion of the cement. The short-term tissue response to the two cements was assessed by quantifying histomorphometric parameters of new bone formation at 2, 4, and 12 weeks postsurgery. Intraoperatively, injection and pressurization of bone cement were well tolerated, with no significant changes in ABP in either group and no detectable circulating monomer in any animal. Several interesting trends were identified in the histomorphometry data. In the trabecular specimens, new bone formation immediately adjacent to the cement mantle was apparently suppressed in the first 2 weeks postsurgery, increased dramatically at 4 weeks, and then returned to baseline values by 12 weeks. This pattern was seen with both Palacos and 2-SC. In the cortical specimens, new bone formation was reduced on the endosteal surface when compared with the periosteal surface, with this effect being more noticeable at 2 and 4 weeks than at 12 weeks. There were no significant histopathological findings in either the bone or the draining lymph nodes. These data indicate that the biological response to 2-SC is substantially equivalent to that of Palacos R. Additional testing in a functional, load-bearing animal model is now recommended to more fully characterize the long-term biological response to 2-SC and to determine the mechanical performance of this new cement in vivo.

Animals↗

Comparative study of bone cements prepared with either HA or alpha-TCP and functionalized methacrylates.

The properties of bone cements prepared with both hydroxyapatite (HA) and alpha-tricalcium phosphate (alpha-TCP) and methacrylates containing acidic or basic groups are the main interest of this article. The presence of methacrylic acid or diethyl amino ethyl methacrylate as comonomers in the bone cement and both ceramic types as filler were found not to affect the amount of residual monomer, which was generally less than 4.5 wt%. In contrast, setting times, maximum temperature, and glass transition temperature were found to be composition dependent. For samples with acidic comonomer, a faster setting time, a higher maximum temperature, and higher glass transition temperatures were observed compared to those with the basic comonomer. The presence of the fillers slightly increased the setting time but did not affect the other parameters. The mechanical properties of the filled bone cements depended mainly on composition and type of testing. Both HA or alpha-TCP filled systems fulfilled the minimum compressive strength required for bone cement application, although a significantly lower value was observed for the alkaline comonomer systems. The minimum bending strength was not satisfied by any of these formulations. The tensile and shear strength of these composites ranged from 20 to 37.9 and from 18 to 27 MPa, respectively. In all cases it was higher for bone cements containing methacrylic acid. The results of this study suggest that the properties of dry unfilled bone cements prepared with MAA are comparable to CMW 3 in mechanical terms but inferior in their setting properties.

Bone Cements↗