Analysis of the shelf life of a two-solution bone cement

Two-solution bone cement consists of methyl methacrylate monomer and poly(methyl methacrylate) polymer dissolved together to yield a viscous solution. Two solutions are used such that the initiator, benzoyl peroxide (BPO), is placed in one solution and the activator, N,N, dimethyl-para-toluidine, is placed in the other. This approach to bone cement provides for a simplified use during surgery and eliminates some of the sources of porosity formation. However, the BPO-containing solution cement will spontaneously polymerize over time and will limit the useful shelf life of this component of the system. The activator-containing component is much more stable and is not as susceptible to spontaneous polymerization. In making two-solution cements, it is envisioned that antibiotics may be incorporated and that the polymer may be sterilized using gamma(gamma)-irradiation. Therefore, this study investigated the shelf life of the initiator-containing solution bone cement and studied the effects of initiator concentration, gamma-irradiation, gentamicin addition, and the role of storage temperature. Isothermal differential scanning calorimetry (Iso-DSC) techniques were used to monitor the polymerization of BPO-containing solutions. It was found that the shelf life was highly temperature dependent and followed an Arrhenius expression where refrigeration storage (4 degrees C) yielded approximately a 12-month storage time, while 70 degrees C storage results in setting in about 5-7 min. gamma-irradiation and gentamicin addition did not significantly affect the shelf life. Initiator concentration affected storage time with higher levels resulting in shorter shelf life.     

Histological evaluation of the bone response to calcium phosphate cement implanted in cortical bone

The aim of this study was to investigate the physicochemical and biological properties of a newly developed calcium phosphate cement (CaP cement) implanted in cortical bone. CaP cement was injected as a paste into tibia cortical bone defects in goats. Polymethylmethacrylate (PMMA) bone cement was used as a control. The animals were killed after 3 days, 2, 8, 16 and 24 weeks. X-ray diffraction and Fourier transform infrared spectroscopy performed at retrieved samples showed that the CaP cement had set as a carbonate apatite and remained stable over time. Light microscopic evaluation showed that after 2 weeks the cement was in tight contact with the bone without any inflammatory reaction or fibrous encapsulation. At later time points, the CaP cement implants were totally covered by a thin layer of bone and osteoclasts, present at the interface, which were clearly resorbing the cement. At locations where CaP cement was resorbed, new bone was deposited. Transmission electron microscopy revealed that indeed a seamless contact existed between CaP cement and bone, as characterized by the occurrence of an electron dense line of 50-60 nm thick that covered the CaP cement. Osteoblasts, in contact with the cement, were depositing new bone. Although the bulk of the material was still in situ after 24 weeks, the progressive osteoclast resorption of the cement followed by new bone formation suggests that all of the material may be replaced eventually. In contrast to the CaP cement, the PMMA reference cement was always surrounded by a thin fibrous capsule. The results indicate that the investigated CaP cement is biocompatible, osteoconductive as well as osteotransductive and is a candidate material for use as a bone substitute.     

Evaluation of a resorbable, in situ setting bone substitute in a sheep model

The gold standard for bone substitution is the autologous bone graft, but because of its limited supply and the associated morbidity, the search for synthetic alternatives is necessary. A new in situ setting tricalcium phosphate cement was implanted in a trepanation defect (9.4 mm diameter, 10 mm depth) in the distal femoral epiphysis of sheep. Empty cavities and autologous bone graft were used as controls. Histologic and histomorphometric examinations were carried out after 12 weeks. Nearly 90% of the implanted cement was resorbed and replaced by ingrown bone with close contact between surrounding bone, new bone, and remaining cement particles. The amount of bone in the defect area was significantly higher in defects filled with cement relative to defects filled with autologous bone graft (mean 27 vs. 21%, 95% confidence intervals 23 to 31 and 18 to 23, p = 0.026). In conclusion, this new in situ setting cement is bioactive, resorbable, and osteoconductive. It will be useful as an alternative to autologous bone graft to fill stable defects.     

A novel high-viscosity, two-solution acrylic bone cement: effect of chemical composition on properties.

Solutions of poly(methyl methacrylate) (PMMA) powder predissolved in methyl methacrylate (MMA) have been developed as an alternative to current powder/liquid bone cements. They utilize the same addition polymerization chemistry as commercial cements, but in mixing and delivering via a closed system, porosity is eliminated and the dependence of material properties on the surgical technique is decreased. Twelve different sets of compositions were prepared, with two solutions of constant polymer-to-monomer ratio (80 g of PMMA/100 mL of MMA) and all combinations of four benzoyl peroxide (BPO) initiator levels added to the first solution and three N, N-dimethyl-p-toluidine (DMPT) activator levels added to the second. These compositions were tested, along with Simplex-P bone cement, for effects of BPO and DMPT concentrations on polymerization exotherm, setting time, flexural strength, modulus, and maximum strain. The results show that each of these dependent variables was affected significantly by the individual concentrations of BPO and DMPT and their interactions. The flexural strength, modulus, and polymerization exotherm reached their maximums at about a 1:1 molar ratio of BPO to DMPT. Most compositions had exotherms, setting times, and maximum strains within the range of commercial cements and flexural strengths and moduli up to 54 and 43% higher than Simplex-P, respectively.     

Quantitative analysis of monomer vapor release from two-solution bone cement by using a novel FTIR technique

Methyl methacrylate monomer can evaporate from bone cement to reach cytotoxic levels of concentrations in the implant bed of total joint prosthesis. Therefore, this study was performed by using a novel Fourier transform infrared spectroscopy method to quantify the release of monomer vapor from experimental two-solution bone cement in vitro during polymerization, to examine the effect of surface area versus cement mass, and to explore the effect of initiation chemistry. The results revealed that monomer vapor release is a surface phenomenon. In addition, initiation chemistry plays a major role in controlling the reaction time, and therefore heat concentration and dissipation, which resulted in a higher absorbance peak as initiation chemicals concentration increased. It was concluded that using the FTIR to monitor MMA vapors is an effective technique to obtain quantitative information about monomer vapor release from bone cements during polymerization and provides insight on the polymerization kinetics of two-solution acrylic bone cement.     

Long-term evaluation of a calcium phosphate bone cement with carboxymethyl cellulose in a vertebral defect model

We investigated histological and compressive properties of a calcium phosphate bone cement (BoneSource (CPC); Stryker Orthopaedics, Mahwah, New Jersey) plus carboxymethyl cellulose (CMC) using a sheep vertebral bone void model. Bone voids were surgically created in L3 and L5 in each of 40 sheep, and the voids were filled with the cement. Histological and radiographic evaluations were performed on one vertebral body from each animal at either: 0, 3, 6, 12, 24, or 36 months after surgery; mechanical testing was performed on operated and non-operated vertebral bodies from 35 sheep. Undecalcified sections were digitized, and the area of the original defect, new bone formation, empty space, fibrous tissue, and residual cement were quantified with histomorphometry. Decalcified sections were evaluated qualitatively. The cement was biocompatible, extremely osteoconductive and underwent steady resorption and replacement by bone and bone marrow. Histomorphometry showed variations in the rate of cement remodeling among animals in each time group, but on average, at 36 months the original defect area was occupied by approximately 14% bone, 82% cement, and 4% bone marrow. Even in animals that had greater resorption of cement, there was good bone ingrowth with no fibrous tissue. Compressive testing did not reveal a significant difference in the mechanical properties between vertebral bodies augmented with cement and non-augmented controls, irrespective of the postoperative time. BoneSource mixed with CMC had adequate osteoconductivity, biocompatibility, and adequate compressive strength. There was variability among animals, but histology suggests that considerable cement was still present in most samples after 36 months.     

Degree of polymerization of acrylic bone cement.

Self-curing powder-liquid admixed acrylic systems are used for internal fixation fo total hip and total knee prostheses. Gel permeation chromatography revealed that the polymer chain length distributions of set cements were basically unaffected by their curing pressures. However, a decrease of approximately 11% in porosity coupled with a measured increase in mechanical strengths could be induced through the use of high curing pressures well beyond those attainable by the surgeon in the current arthroplasties. The conclusion of the investigation was that, to improve such cements, attention should be focused on elimination of porosity rather than attempting to produce higher degree of polymerization.     

Vertebroplasty using bisphosphonate-loaded calcium phosphate cement in a standardized vertebral body bone defect in an osteoporotic sheep model

In the context of bone regeneration in an osteoporotic environment, the present study describes the development of an approach based on the use of calcium phosphate (CaP) bone substitutes that can promote new bone formation and locally deliver in situ bisphosphonate (BP) directly at the implantation site. The formulation of a CaP material has been optimized by designing an injectable apatitic cement that (i) hardens in situ despite the presence of BP and (ii) provides immediate mechanical properties adapted to clinical applications in an osteoporotic environment. We developed a large animal model for simulating lumbar vertebroplasty through a two-level lateral corpectomy on L3 and L4 vertebrae presenting a standardized osteopenic bone defect that was filled with cements. Both 2-D and 3-D analysis of microarchitectural parameters demonstrated that implantation of BP-loaded cement in such vertebral defects positively influenced the microarchitecture of the adjacent trabecular bone. This biological effect was dependent on the distance from the implant, emphasizing the in situ effect of the BP and its release from the cement. As a drug device combination, this BP-containing apatitic cement shows good promise as a local approach for the prevention of osteoporotic vertebral fractures through percutaneous vertebroplasty procedures.     

Computational modelling of bone cement polymerization: Temperature and residual stresses

The two major concerns associated with the use of bone cement are the generation of residual stresses and possible thermal necrosis of surrounding bone. An accurate modelling of these two factors could be a helpful tool to improve cemented hip designs. Therefore, a computational methodology based on previous published works is presented in this paper combining a kinetic and an energy balance equation. New assumptions are that both the elasticity modulus and the thermal expansion coefficient depend on the bone cement polymerization fraction. This model allows to estimate the thermal distribution in the cement which is later used to predict the stress-locking effect, and to also estimate the cement residual stresses. In order to validate the model, computational results are compared with experiments performed on an idealized cemented femoral implant. It will be shown that the use of the standard finite element approach cannot predict the exact temporal evolution of the temperature nor the residual stresses, underestimating and overestimating their value, respectively. However, this standard approach can estimate the peak and long-term values of temperature and residual stresses within acceptable limits of measured values. Therefore, this approach is adequate to evaluate residual stresses for the mechanical design of cemented implants. In conclusion, new numerical techniques should be proposed in order to achieve accurate simulations of the problem involved in cemented hip replacements.     

Long-term reaction to bone cement in osteoporotic bone: new bone formation in vertebral bodies after vertebroplasty

Elderly patients frequently suffer from osteoporotic vertebral fractures resulting in the need of vertebroplasty or kyphoplasty. Nevertheless, no data are available about the long-term consequences of cement injection into osteoporotic bone. Therefore, the aim of the present study was to evaluate the long-term tissue reaction on bone cement injected to osteoporotic bone during vertebroplasty. The thoracic spine of an 80-year-old female was explanted 3.5 years after vertebroplasty with polymethylmethacrylate. The treatment had been performed due to painful osteoporotic compression fractures. Individual vertebral bodies were cut in axial or sagittal sections after embedding. The sections were analysed using contact radiography and staining with toluidine blue. Furthermore, selected samples were evaluated with scanning electron microscopy and micro-compted tomography (in-plane resolution 6 microm). Large amounts of newly formed callus surrounding the injected polymethylmethacrylate were detected with all imaging techniques. The callus formation almost completely filled the spaces between the vertebral endplate, the cancellous bone, and the injected polymethylmethacrylate. In trabecular bone microfractures and osteoclast lacuna were bridged or filled with newly formed bone. Nevertheless, the majority of the callus formation was found in the immediate vicinity of the polymethylmethacrylate without any obvious relationship to trabecular fractures. The results indicate for the first time that, contrary to established knowledge, even in osteoporosis the formation of large amounts of new bone is possible.     

Nano-mechanics of bone and bioactive bone cement interfaces in a load-bearing model

Many bioactive bone cements were developed for total hip replacement and found to bond with bone directly. However, the mechanical properties at the bone/bone cement interface under load bearing are not fully understood. In this study, a bioactive bone cement, which consists of strontium-containing hydroxyapatite (Sr-HA) powder and bisphenol-alpha-glycidyl dimethacrylate (Bis-GMA)-based resin, was evaluated in rabbit hip replacement for 6 months, and the mechanical properties of interfaces of cancellous bone/Sr-HA cement and cortical bone/Sr-HA cement were investigated by nanoindentation. The results showed that Young's modulus (17.6+/-4.2 GPa) and hardness (987.6+/-329.2 MPa) at interface between cancellous bone and Sr-HA cement were significantly higher than those at the cancellous bone (12.7+/-1.7 GPa; 632.7+/-108.4 MPa) and Sr-HA cement (5.2+/-0.5 GPa; 265.5+/-39.2 MPa); whereas Young's modulus (6.3+/-2.8 GPa) and hardness (417.4+/-164.5 MPa) at interface between cortical bone and Sr-HA cement were significantly lower than those at cortical bone (12.9+/-2.2 GPa; 887.9+/-162.0 MPa), but significantly higher than Sr-HA cement (3.6+/-0.3 GPa; 239.1+/-30.4 MPa). The results of the mechanical properties of the interfaces were supported by the histological observation and chemical composition. Osseointegration of Sr-HA cement with cancellous bone was observed. An apatite layer with high content of calcium and phosphorus was found between cancellous bone and Sr-HA cement. However, no such apatite layer was observed at the interface between cortical bone and Sr-HA cement. And the contents of calcium and phosphorus of the interface were lower than those of cortical bone. The mechanical properties indicated that these two interfaces were diffused interfaces, and cancellous bone or cortical bone was grown into Sr-HA cement 6 months after the implantation.     

Histological and mechanical evaluation of self-setting calcium phosphate cements in a sheep vertebral bone void model

We investigated the histological and compressive properties of three different calcium phosphate cements (CPCs) using a sheep vertebral bone void model. One of the CPCs contained barium sulfate to enhance its radiopacity. Bone voids were surgically created in the lumbar region of 23 ovine spines - L3, L4, and L5 (n = 69 total vertebral bodies) - and the voids were filled with one of the three CPCs. A fourth group consisted of whole intact vertebrae. Histologic evaluation was performed for 30 of the 69 vertebrae 2 or 4 months after surgery along with radiographic evaluation. Compressive testing was performed on 39 vertebrae 4 months after surgery along with micro-CT analysis. All three CPCs were biocompatible and extremely osteoconductive. Osteoclasts associated with adjacent bone formation suggest that each cement can undergo slow resorption and replacement by bone and bone marrow. Compressive testing did not reveal a significant difference in the ultimate strength, ultimate strain, and structural modulus, among the three CPCs and intact whole vertebrae. Micro-CT analysis revealed good osseointegration between all three CPCs and adjacent bone. The barium sulfate did not affect the CPCs biocompatibility or mechanical properties. These results suggest that CPC might be a good alternative to polymethylmethacrylate for selected indications.     

In vivo bone response to porous calcium phosphate cement

We conducted an in vivo experiment to evaluate the resorption rate of a calcium phosphate cement (CPC) with macropores larger than 100 microm, using the CPC called Biocement D (Merck Biomaterial, Darmstadt, Germany), which after setting only shows pores smaller than 1 microm. The gas bubble method used during the setting process created macroporosity. Preset nonporous and porous cement implants were inserted into the trabecular bone of the tibial metaphysis of goats. The size of the preset implants was 6 mm and the diameter of the drill hole was 6.3 mm, leaving a gap of 0.3 mm between implant surface and drill wall. After 2 and 10 weeks, the animals were euthanized and cement implants with surrounding bone were retrieved for histologic evaluation. Light microscopy at 2 weeks revealed that the nonporous implants were surrounded by connective tissue. On the cement surface, we observed a monolayer of multinucleated cells. Ten weeks after implantation, the nonporous implants were still surrounded by connective tissue. However, a thin layer of bone now covered the implant surface. No sign of cement resorption was observed. In contrast, the porous cement evoked a completely different bone response. At 2 weeks, bone formation had already occurred inside the implant porosity. Bone formation even appeared to occur as a result of osteoinduction. Also, at their outer surface, the porous implants were completely surrounded by bone. At 2 weeks, about 31% of the initial cement was resorbed. After 10 weeks, 81% of the initial phosphate cement was resorbed and new bone was deposited. On the basis of these observations, we conclude that the creation of macropores can significantly improve the resorption rate of CPC. This increased degradation is associated with almost complete bone replacement.     

Tissue response to a newly developed calcium phosphate cement containing succinic acid and carboxymethyl-chitin

We developed a new calcium phosphate cement containing succinic acid and carboxymethyl-chitin in the liquid component. In this study, the biocompatibility and osteoconductivity of this new cement were investigated. After mixing, cement in putty form was implanted immediately between the periosteum and parietal bone and in the subcutaneous tissues of rats. In control cement, distilled water was used instead of the liquid component. In addition to histological evaluations, analyses with X-ray diffraction and Fourier transform infrared were performed for the subcutaneously implanted cements. Histological examination showed slight inflammation around the new cement on the bone and in the subcutaneous tissue at 1 week after surgery. At 2 weeks, the cement was partially bound to the parietal bone. The extent of the surface of the new cement directly in contact with the bone increased with time, and most of the undersurface of the new cement bound to the host parietal bone by 8 weeks. Analysis by X-ray diffraction showed that the new cement in the subcutaneous tissue was transformed into hydroxyapatite by 8 weeks. These results indicate that this new calcium phosphate cement is useful as a bone substitute material.     

Biocompatibility of a new radiopaque iodine-containing acrylic bone cement

Radiopacity in the vast majority of the commercially available acrylic bone cements that are used clinically is provided by particles of either BaSO(4) or ZrO(2). Literature reports have shown these agents to have a detrimental effect on some mechanical properties of the cements as well as on its biological response. We, therefore, have developed a new type of bone cement, for which radiopacity results from the presence of an iodine-containing methacrylic copolymer. The focus of the present work was the comparison of the biocompatibility of this new cement and a commercially available cement that contains barium sulfate. In vitro experiments show that both cements are cytocompatible materials, for which no toxic leachables are found. Implantation of the cements in a rabbit for three months resulted in the occasional presence of a thin fibrous tissue at the cement-bone interface, which is common for acrylic bone cements. Consideration of all the results led to the conclusion that the new cement is as biocompatible as the BaSO(4)-containing one.     

Normal and osteopenic bone-derived osteoblast response to a biomimetic gelatin-calcium phosphate bone cement

We have recently developed a new calcium phosphate bone cement enriched with gelatin (GEL-CP), which exhibits improved mechanical properties with respect to the control cement (C-CP). In a previous study, we demonstrated the good response of osteoblast-like cells to the new biomimetic bone cement. Herein, we extend the investigation to primary culture of osteoblasts derived from healthy and pathological bones. Osteoblasts derived from normal (N-OB) and osteopenic (O-OB) sheep bones were cultured on samples of GEL-CP, and their behavior was compared with that of cells cultured on C-CP as control. Cell morphology, proliferation, and differentiation were evaluated at 3 and 7 days. SEM analysis revealed that both N-OB and O-OB showed a normal morphology when cultured on GEL-CP. Biological tests demonstrated that the gelatin-enriched cement improves osteoblasts' activity and differentiation of O-OB cultures, with respect to the control samples. The data indicate that the new composite cement positively stimulates alkaline phosphatase activity, collagen type I, and osteocalcin production, not only in N-OB, but also in O-OB culture. The improvement due to the presence of gelatin suggests that the biomimetic composite material could be successfully applied as bone substitute also in the presence of osteopenic bone.     

VersaBond bone cement prospective randomized study of the clinical properties of a new bone cement in total knee replacement

VersaBond is a newly developed bone cement. To investigate its clinical performance, VersaBond was compared to Palacos R in a prospective randomized study in total knee replacement. Fifty-nine patients (61 knees) undergoing total knee replacement were randomized to either VersaBond or Palacos R bone cement and followed for 24 months using radiostereometric analysis (RSA). Up to 2 years there were no significant differences in clinical performance between the two cements. The mean/median values for implant migration were very similar for the two bone cements, as were the dispersion, and distribution of outliers. Also the proportion "stable" and "continuously migrating" implants was similar between the two cements. The result of this study indicates that VersaBond bone cement will perform at least equally as well as Palacos R in total knee replacement as regards as aseptic loosening.     

Comprehensive biocompatibility testing of a new PMMA-HA bone cement versus conventional PMMA cement in vitro

For more than 50 years PMMA bone cements have been used in orthopaedic surgery. In this study attempts were made to show whether cultured human bone marrow cells (HBMC) show an osteogenetic response resulting in new bone formation, production of extracellular matrix (ECM) and cell differentiation when they were cultured onto polymerized polymethylmethacrylate (PMMA)-hydroxyapatite (HA), conventional PMMA bone cement being taken as reference. Biocompatibility parameters were collagen-I and -III synthesis, the detection of the osteoblast markers alkaline phosphatase (ALP) and osteocalcin, the number of adherent cells and the cytodifferentiation of immunocompetent cells. Cement surface structure, HA stability in culture medium and chemical element analysis of specimens were considered. Fresh marrow cells were obtained from the human femora during hip replacement. Incubation time was up to ten weeks. We used atomic forced microscopy (AFM) and scanning electron microscopy (SEM) for cement specimen analysis. Fluorescent activated cell sorter (FACS), immunohistochemical staining, SEM and light microscopy (LM) served us to judge the cellular morphology. Products of the extracellular matrix were analyzed by protein dot blot analysis, SEM energy dispersive X-ray analysis (SEM-EDX) and Ca²⁺/PO₄ ^3- detection. HA particles increased the osteogenetic potential of PMMA bone cement regarding the cellular production of collagen, alkaline phosphatase (AP), the number of osteoblasts and the cellular differentiation pattern in vitro. Both tested cements showed good biocompatibility in a human long-term bone marrow cell-culture system.     

椎体后凸成形骨水泥注射治疗的有限元模型数字化评价

背景:由于经皮椎体后凸成形的治疗原理、远期疗效、并发症均与其生物力学密切相关,其生物力学引起了广泛关注。目的:建立椎体后凸成形骨水泥注射治疗后的生物力学变化及骨水泥泄漏虚拟数字化评价系统。方法:在前期实验已建立的L3-L5三维模型的基础上进行椎体后凸成形骨水泥注射操作,并导入Abaqus2016软件将模型立体化,进行有限元分析,分析骨水泥注射方式、注射压力及注射量对L4骨折椎体终板应力的影响。结果与结论:①模拟经皮椎体后凸成形手术操作填充骨水泥后,L4骨折椎体终板在骨水泥的承载分压作用下应力明显降低。不同注射方式对L4骨折椎体终板所受应力影响不显著(P> 0.05),但双侧注射使骨水泥分布更加均匀,效果最好;②不同注射压力对L4骨折椎体终板所受应力影响不显著(P> 0.05),但随着注射压力的增加,骨水泥分布更加分散,更容易出现渗漏;③随着骨水泥注射剂量逐渐增加,L4骨折椎体终板应力逐渐降低(P<0.05),注射2 mL时不能恢复椎体的生理刚度,4 mL时骨水泥分布更加集中,8 mL时达到屈服点;④骨水泥注射后,下位椎体上终板比上位椎体下终板更容易出现再骨折的情况:⑤结果表明,模拟手术前后L4椎体终板应力发生明显转移,即L4上终板应力增加,L4下终板应力减少;不同注射方式对手术结果影响不大,但双侧注入的骨水泥分布更加均匀,降低了术后再次骨折和塌陷的概率;选用低注射压力可降低术后骨水泥泄露风险;4 mL注射量既能使病椎恢复较好的刚度及生理曲度又未达到屈服点而引起再次骨折。