Investigation of an effervescent additive as porogenic agent for bone cement macroporosity

Calcium phosphate cements (CPCs) are biocompatible and osteoconductive materials used in dental, craniofacial and orthopaedic applications. One of the most important advantages of these materials is their replacement with bone followed by resorption. Already several attempts have been made to improve the resorption behaviour of calcium phosphate cements by increasing the porosity of the material. In this investigation a mixture of NaHCO(3) and citric acid monohydrate was added to the apatite cement component as an effervescent additive for producing interconnected macropores into the cement matrix. Mercury intrusion porosimetry was employed to determine pore volume and pore size distribution in the calcium phosphate cement (CPC) samples. Results showed that addition of only 10 wt % of the effervescent additive (based on the cement powder) to the CPC components lead to producing about 20 V % macropores (with the size of 10 to 1000 mum) into the cement structure. The setting time was measured in an incubator at 37 degrees C and decreased from 40 min for additive-free CPC to about 14 min for CPC containing effervescent additive. Other properties of the CPCs such as compressive strength, phase composition, microstructure morphology and dissolution behavior were evaluated after immersing them in a simulated body fluid solution. The results showed that the rate of formation of poor crystalline apatite phase have been improved by production of macroporosity into the cement matrix.     

Calcium phosphate cement containing resorbable fibers for short-term reinforcement and macroporosity.

Calcium phosphate cement (CPC) sets to form hydroxyapatite and has been used in medical and dental procedures. However, the brittleness and low strength of CPC prohibit its use in many stress-bearing locations, unsupported defects, or reconstruction of thin bones. Recent studies incorporated fibers into CPC to improve its strength. In the present study, a novel methodology was used to combine the reinforcement with macroporosity: large-diameter resorbable fibers were incorporated into CPC to provide short-term strength, then dissolved to create macropores suitable for bone ingrowth. Two types of resorbable fibers with 322 microm diameters were mixed with CPC to a fiber volume fraction of 25%. The set specimens were immersed in saline at 37 degrees C for 1, 7, 14, 28 and 56d, and were then tested in three-point flexure. SEM was used to examine crack-fiber interactions. CPC composite achieved a flexural strength 3 times, and work-of-fracture (toughness) nearly 100 times, greater than unreinforced CPC. The strength and toughness were maintained for 2-4 weeks of immersion, depending on fiber dissolution rate. Macropores or channels were observed in CPC composite after fiber dissolution. In conclusion, incorporating large-diameter resorbable fibers can achieve the needed short-term strength and fracture resistance for CPC while tissue regeneration is occurring, then create macropores suitable for vascular ingrowth when the fibers are dissolved. The reinforcement mechanisms appeared to be crack bridging and fiber pullout, the mechanical properties of the CPC matrix also affected the composite properties.     

丙烯酸树脂骨水泥复合材料对软骨下骨诱发膝骨关节炎的影响

背景：丙烯酸树脂骨水泥植入人体发生硬化后其可抵抗78-93 MPa的强度,但骨水泥凝固过程中释放大量的热能,会杀死正常细胞导致周围组织坏死。 目的：观察丙烯酸树脂骨水泥复合材料替代软骨下骨后诱发兔膝骨关节炎的特点。 方法：将30只日本大耳白兔随机均分为5组,实验A、B、C、D组在刮除右侧膝关节胫骨平台内侧软骨下骨后,均植入聚甲基丙烯酸甲酯粉剂/羟基磷灰石复合材料,空白对照组仅暴露左侧膝关节胫骨平台内侧骨膜。实验组A、B、C、D组分别在软骨下骨刮除后3,6,9,12周处死动物,切取复合材料上方1.5 mm处的软骨下骨标本进行苏木精-伊红染色、基质金属蛋白酶表达分析,同时检测关节液中白细胞介素1β及肿瘤坏死因子α水水平。 结果与结论：实验C组的Mankin骨关节炎分级高于空白对照组和实验A组(P < 0.05),实验组D的Mankin骨关节炎分级高于实验B组(P < 0.05)。基质金属蛋白酶1的灰度值比较：空白对照组> 实验A组> 实验B组>实验C组> 实验D组(P < 0.05)。白细胞介素1 β及肿瘤坏死因子α水平比较：实验D组> 实验C组> 实验B组> 实验A组> 空白对照组(P < 0.05)。表明丙烯酸树脂骨水泥复合材料替代软骨下骨后能引发膝骨关节炎,并且会导致基质金属蛋白酶1及细胞因子水平的升高。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Alumina as a filler for bone cement: a feasibility study

A composite bone cement of Alcoa A-10 Alumina and very finely ground poly(methyl methacrylate) beads (PMMA) was fabricated. It was tested in an attempt to improve on the conventionally used pure PMMA bone cement.

By knowing the densities of the powders and their volumes, the mass of each was calculated for the most efficient packing of PMMA and Al₂O₃ powders and a 65% PMMA: 35% Al₂O₃ ratio by weight composition was determined. This was tested, as well as the pure cement so comparisons could be made. Cylinders for the strength tests were also made of silane treated Al₂O₃.

The compositions were tested for compressive and tensile strengths. The pure PMMA, composite and silane treated composite had compressive strengths of 79.64 ± 13.0, 83.17 ± 4.8, and 71.52±8.6 MPa and the tensile strengths were 6.69 ±0.6, 5.12 ±0.3, and 7.12±0.5 MPa respectively. Also the 65%–35% PMMA-Al₂O₃ composite required 64% less monomer for mixing than did the pure cement which is thought to be better for tissue healing. The maximum temperature attained from room temperature was 110°–115°C for both cements. The composite took 6.5 min longer to reach its peak temperature than did the pure cement. The bone cements were implanted for one week in a rabbit and both compositions seemed acceptable by the tissue.     

Adhesive bone cement containing hydroxyapatite particle as bone compatible filler.

Acrylic bone cement containing hydroxyapatite (HA) as a filler was developed using 4-methacryloyloxyethyl trimellitate anhydride (4-META) to promote adhesion both to bone and HA. The mechanical strengths of the cement did not decrease significantly with increasing HA in the cement by 4-META. However, strengths decreased with increasing HA content in the absence of 4-META. Scanning electron micrographic examination of fractured surfaces of the cement clearly showed that the HA particles adhered to the matrix resin when 4-META was added. Thus, it was important to maintain the original mechanical strengths for 4-META. The HA particles along the surface increased with increased HA content in the cement. The cement adhered to bone with a tensile bond strength was higher than 10 MPa.     

Open wedge tibial osteotomy with acrylic bone cement as bone substitute

We studied the results of 245 valgus producing high tibial osteotomies performed with the use of an opening wedge technique and rigid internal fixation followed by early passive and active motion of the knee. Previous studies have used iliac bone grafts or hemicollastasis held by an external fixator for opening the osteotomy. In our series the opening was obtained by a block of cement interposed in the postero-medial part of the osteotomy. This series confirms that the opening wedge osteotomy allows good accuracy for the correction. Ninety-three percent of the knees had a correction adjusted between 180 and 187 degrees for the hip-knee-ankle angle. Survivorship analysis showed an expected rate of survival, with conversion to a total knee on the end point, of 94% at 5 years, 85% at 10 years and 68% at 15 years. Conversion to a total knee arthroplasty was accomplished without difficulty in the patients who had this procedure done. We recommend opening wedge tibial osteotomy with acrylic cement bone cement as bone substitute, rigid internal fixation, and early motion for patients who undergo high tibial osteotomy.     

Copolymerization of photocrosslinkable anhydride monomers for use as a biodegradable bone cement

A multifunctional anhydride monomer, methacrylated sebacic anhydride (MSA), was synthesized and copolymerized with methacrylic anhydride via photoinitiated polymerization to form highly crosslinked, degradable networks. This material system was investigated as a potential degradable bone cement. Several aspects were examined, including curing characteristics, degradation rates and mechanical properties. These copolymer networks reached high double-bond conversions on clinically acceptable time scales (<5 min). Furthermore, these divinyl monomer copolymerizations exhibit features of classical crosslinking polymerizations, including autoacceleration, autodeceleration and limited double-bond conversion. Additionally, the networks degrade via a surface erosion mechanism by which the degradation rate can be controlled through varying the degree of oligomerization of the multifunctional monomer backbone, varying the copolymer precursor composition and changing the monomer backbone chemistry. Finally, the copolymer was found to have improved mechanical properties over homopolymerized MSA. Compressive strengths as high as 78 +/- 5 MPa were attained with a 70/30 wt% MSA/methacrylic anhydride copolymer, which are comparable to measured (91 +/- 7 MPa) and literature (approx. 100 MPa) values for conventional poly(methyl methacrylate) bone cement.     

Influence of the activator in an acrylic bone cement on an array of cement properties

In all but one of the acrylic bone cement brands used in cemented arthroplasties, N,N-dimethyl-4-toluidine (DMPT) serves as the activator of the polymerization reaction. However, many concerns have been raised about this activator, all related to its toxicity. Thus, various workers have assessed a number of alternative activators, with two examples being N,N-dimethylamino-4-benzyl laurate (DMAL) and N,N-dimethylamino-4-benzyl oleate (DMAO). The results of limited characterization of cements that contain DMAL or DMAO have been reported in the literature. The present work is a comprehensive comparison of cements that contain one of these three activators, in which the values of a large array of their properties were determined. These properties range from the setting time and maximum exotherm temperature of the curing cement to the variation of the loss elastic modulus of the cured cement with frequency of the applied indenting force in dynamic nanoindentation tests. The present results, taken in conjunction with those presented in previous reports by the present authors and co-workers on other properties of these cements, indicate that both DMAL and DMPT are suitable alternatives to DMPT.     

Foamed surfactant solution as a template for self-setting injectable hydroxyapatite scaffolds for bone regeneration

The application of minimally invasive surgical techniques in the field of orthopaedic surgery has created a growing need for new injectable synthetic materials that can be used for bone grafting. In this work a novel fully synthetic injectable calcium phosphate foam was developed by mixing α-tricalcium phosphate (α-TCP) powder with a foamed polysorbate 80 solution. Polysorbate 80 is a non-ionic surfactant approved for parenteral applications. The foam was able to retain the porous structure after injection provided that the foamed paste was injected shortly after mixing (typically 2.5 min), and set through the hydrolysis of α-TCP to a calcium-deficient hydroxyapatite, thus producing a hydroxyapatite solid foam in situ. The effect of different processing parameters on the porosity, microstructure, injectability and mechanical properties of the hydroxyapatite foams was analysed, and the ability of the pre-set foam to support osteoblastic-like cell proliferation and differentiation was assessed. Interestingly, the concentration of surfactant needed to obtain the foams was lower than that considered safe in drug formulations for parenteral administration. The possibility of combining bioactivity, injectability, macroporosity and self-setting ability in a single fully synthetic material represents a step forward in the design of new materials for bone regeneration compatible with minimally invasive surgical techniques.     

Influence of filler content on static properties of glass-reinforced bone cement

A commercial acrylic bone cement was modified by the incorporation of different weight fractions of glass spheres. The influence of the filler proportion on the mechanical behavior was assessed. Composite cements were prepared by replacing part of the powder phase of the cement by an equivalent weight of glass particles, which resulted in an increase in the liquid-to-powder (L/P) ratio of the polymeric matrix. Dynamic mechanical analysis revealed an increase in residual monomer content with increasing filler proportion as a consequence of the increase in L/P. Flexural, compressive, and fracture properties of the cement with varying amounts of glass particles were measured. It was found that up to 50 wt% glass particles could be added with significant increases in flexural modulus and fracture toughness. The mechanical behavior was explained in terms of both the reinforcing effect of the filler and the plasticizing effect of the monomer. Glass-filled bone cements displayed superior workability compared with the standard cement, which was attributed to a decrease in the viscosity of the initial mix and the surface characteristics of the glass particles. The observed increase in fracture toughness could be rationalized through the application of proposed mechanisms for toughening of particle-reinforced polymers.     

Influence of mixing technique on some properties of PMMA bone cement

PMMA bone cements (Refobacin-Palacos R, Sulfix 6, AKZ, and CMW bone cement, types I and II), from six different clinics, were investigated in three stages. In the first stage, studies of density, hardness, flexural strength, and compressive strength were made, as well as molecular weight measurements and microscopic investigations. These studies reflected the current state of techniques of application used in operating theaters. They revealed wide variations in the properties of the materials studied. Secondly, a comprehensive study of the process-technology in the laboratory was performed. The following variables were investigated or discussed: mixing vessel, order of the individual components, mixing time, rate of mixing, pressure application on the mixed bone cement, kneading, cement thickness, pouring into the syringe, contact force during polymerization, and preparation quantity. The third stage involved the development and clinical testing of an improved mixing technique. Using this improved mixing technique, all three selected clinics achieved far better results with reduced variability. A comparison between a centrifuging technique after mixing and our improved, but conventional, mixing technique, displays advantages for the latter. The question regarding a correlation between cement specimens of high porosity and early implant loosening could not be answered on the basis of the 43 PMMA bone cement explants investigated (implanted 6 months to 15 years). In some cases, the studies revealed that the bone cement manufacturers should be required to revise and quantify existing instructions for use. The users, on the other hand, should give more consideration to the mixing technique and its consequences.     

Adhesion enhancement of steel fibers to acrylic bone cement through a silane coupling agent

The use of a silane coupling agent (methacryloxypropyl-trichlorosilane) to improve the mechanical properties of steel fiber-reinforced acrylic bone cements was assessed. Changes to the tensile and fracture properties of bone cements reinforced with silane-coated or uncoated 316L stainless steel fibers of different aspect ratios were studied. Contact-angle measurements indicated that the coupling agent coats the metal surface through room temperature treatments in a short time (within 2 h). Push-out tests indicated that the interfacial shear strength of silane-coated 316L stainless steel rods is 141% higher than the uncoated rods. The elastic moduli, ultimate stresses, and fracture toughness of the silane-coated, steel fiber-reinforced bone cements are significantly higher than the bone cements reinforced with uncoated steel fibers. There were no differences in the tensile mechanical properties of the silane-coated or uncoated, steel fiber-reinforced cements after aging in a physiological saline solution, indicating that the bonding effectiveness is decreased by the intrusion of water at the metal-polymer interface. Because of possible biocompatibility issues with leaching of the silane coupling agent and no long-term mechanical benefit in simulated aging experiments, the use of these agents is not recommended for in vivo use.     

高黏度骨水泥与传统骨水泥治疗骨质疏松性椎体压缩性骨折的疗效比较

目的比较高黏度骨水泥与传统聚甲基丙烯酸甲酯(PMMA)骨水泥治疗骨质疏松性椎体压缩性骨折的疗效,探讨高黏度骨水泥在临床应用中的优势。方法选择2009年7月~2013年7月治疗并获得随访160例骨质疏松性椎体压缩性骨折患者,其中男性64例,女性96例;年龄61~88岁,平均年龄69.1岁。分高黏度骨水泥组[91例(112个椎体)]和传统骨水泥组[69例(86个椎体)]。高黏度骨水泥组,采用以色列Disc-O-Tech公司Confidence骨水泥,施行经皮椎体成形术(PVP);传统骨水泥组,采用PMMA骨水泥,施行PVP。术后对比两组患者视觉疼痛模拟评分(VAS)、责任椎Cobb角的恢复情况及术后骨水泥渗漏情况,并随访观察。结果高黏度骨水泥组与传统骨水泥组VAS评分(1.5±0.8vs1.4±0.9)比较差异无统计学意义(P0.05);高黏度骨水泥组Cobb角恢复优于传统骨水泥组(13.6°±3.1°vs 19.8°±3.0°),差异有统计学意义(P0.05);高黏度骨水泥组渗漏率远低于传统骨水泥组(19.6%vs 41.9%),差异有统计学意义(P0.05)。所有患者术后获得3~48个月(平均16个月)随访,其中3例出现神经根症状,所有患者未出现感染、肺栓塞等并发症。结论高黏度骨水泥与传统PMMA骨水泥相比,在纠正椎体Cobb角及降低骨水泥渗漏发生率方面效果更佳,明显提高了PVP的安全性及有效性。     

Evaluation of feasibility of hydroxyapatite putty as a local hemostatic agent for bone

Although bone wax is known to cause an inflammatory reaction in soft tissue and a delay of bone healing, it is usually the first choice to arrest bleeding from bone. Hydroxyapatite (HAP) putty is proposed here. This study evaluated the feasibility of HAP putty with respect to whether or not it has potential value as a hemostatic agent for bone. First, the adhesive strength of HAP putty to bone was evaluated. The adhesive strength of HAP putty to wet bone was much higher when compared with that of bone wax, even though the adhesive strengths of HAP putty and bone wax to dry bone were equivalent. Next, to evaluate the hemostatic ability of HAP putty, bony defects were made in rabbits. HAP putty could arrest bleeding from bone within 3 min. However, when the hemostasis was performed with bone wax, bleeding was arrested within 8 min. Thus, HAP putty showed better hemostatic ability than bone wax. Finally, the tissue response to HAP putty in rabbit subcutaneous tissue was evaluated. Histological observation revealed a slight inflammatory response around HAP putty, whereas bone wax was surrounded by moderate inflammatory tissue. In conclusion, HAP putty has good potential value to be a hemostatic agent for bone because it has strong adhesion, good hemostatic ability, and biocompatibility.     

Influence of mixing techniques on the physical properties of acrylic bone cement

Palacos R bone cement was prepared using three commercially available mixing techniques, first generation, second generation and third generation, to determine the mechanical properties and porosity contents of the bone cement. The compressive strengths, bending strengths and flexural moduli were expressed as a function of void content. The volume of pores within the cement structure was found to be a contributing factor to the physical properties of acrylic bone cement. The lower the volume of voids in the cement the better the compressive and flexural properties, hence stronger bone cement. It was found that the best results were obtained from cement that had been mixed using the Mitab Optivac or Summit HiVac Syringe systems at a reduced pressure level of between -72 and -86 kPa below atmospheric pressure, resulting in cement of porosity 1.44-3.17%; compressive strength 74-81 MPa; flexural modulus 2.54-2.60 GPa; and flexural strength 65-73 MPa.     

Preparation of acrylic bone cements for vertebroplasty with bismuth salicylate as radiopaque agent

One of the problems of percutaneous vertebroplasty attributed to the use of acrylic cements is related to the radiopacity of the formulation. The use of bismuth salicylate as the radiopaque agent is proposed in this work, taking into account the high radiopacity of organobismuth compounds used in dental applications and the possible analgesic effect of salicylic acid. Various cements formulated with this compound (some of them modified with polyethylene oxide) were examined. Setting parameters, mechanical properties, rheological behaviour, injectability, radiopacity and biocompatibility were studied for a variety of formulations, showing that the cement formulations containing bismuth salicylate have a higher radiopacity and better injection properties than commercial bone cement preparations and present good mechanical properties.     

Ready-to-use injectable calcium phosphate bone cement paste as drug carrier

Current developments in calcium phosphate cement (CPC) technology concern the use of ready-to-use injectable cement pastes by dispersing the cement powder in a water-miscible solvent, such that, after injection into the physiological environment, setting of cements occurs by diffusion of water into the cement paste. It has also been demonstrated recently that the combination of a water-immiscible carrier liquid combined with suitable surfactants facilitates a discontinuous liquid exchange in CPC, enabling the cement setting reaction to take place. This paper reports on the use of these novel cement paste formulations as a controlled release system of antibiotics (gentamicin, vancomycin). Cement pastes were applied either as a one-component material, in which the solid drugs were physically dispersed, or as a two-component system, where the drugs were dissolved in an aqueous phase that was homogeneously mixed with the cement paste using a static mixing device during injection. Drug release profiles of both antibiotics from pre-mixed one- and two-component cements were characterized by an initial burst release of ～7–28%, followed by a typical square root of time release kinetic for vancomycin. Gentamicin release rates also decreased during the first days of the release study, but after ～1 week, the release rates were more or less constant over a period of several weeks. This anomalous release kinetic was attributed to participation of the sulfate counter ion in the cement setting reaction altering the drug solubility. The drug-loaded cement pastes showed high antimicrobial potency against Staphylococcus aureus in an agar diffusion test regime, while other cement properties such as mechanical performance or phase composition after setting were only marginally affected.     

Polymer--calcium phosphate cement composites for bone substitutes

The use of self-setting calcium phosphate cements (CPCs) as bioresorbable bone-replacement implant materials presently is limited to non-load-bearing applications because of their low compressive strength relative to natural bone. The present study investigated the possibility of strengthening a commercially available CPC, alpha-BSM, by incorporating various water-soluble polymers into the cement paste during setting. Several polyelectrolytes, poly(ethylene oxide), and the protein bovine serum albumin (BSA) were added in solution to the cement paste to create calcium phosphate-polymer composites. Composites formulated with the polycations poly(ethylenimine) and poly(allylamine hydrochloride) exhibited compressive strengths up to six times greater than that of pure alpha-BSM material, with a maximum value reached at intermediate polymer content and for the highest molecular weight studied. Composites containing BSA developed compressive strengths twice that of the original cement at protein concentrations of 13-25% by weight. In each case, XRD studies correlate the improvement in compressive strength with reduced crystallite dimensions, as evidenced by a broadening of the (0,0,2) reflection. This suggests that polycation or BSA adsorption inhibits crystal growth and possibly leads to a larger crystal aspect ratio. SEM results indicate a denser, more interdigitated microstructure. The increased strength was attributed to the polymer's capacity to bridge between multiple crystallites (thus forming a more cohesive composite) and to absorb energy through plastic flow.     

Influence of Charnley hip neck-angle inclination on the stresses at stem/cement and bone/cement interfaces

The present work aims to elucidate the influence of neck-stem angle inclination on the principal normal and shear stress distributions and values along the interfaces of the stem/cement and bone/cement in a cemented Charnley curved back femoral component. The same stresses were also examined for the intact bone that was considered as a reference for the obtained results. The interface is considered the weakest link in the structure and its endurance limit to failure is much less than the limit of the adjacent materials. Interface loading is by far the influential aspect governing the induced interface stresses in femoral total hip replacement. Therefore, higher values and nonuniform distribution of stresses at the interface may lead to loosening and crack initiation and propagation that usually precede the stem fracture.     

Repair of segmental bone defects using bioactive bone cement: comparison with PMMA bone cement.

We developed a bioactive bone cement (BABC) that consists of apatite and wollastonite containing glass ceramic (AW-GC) powder and bisphenol-A-glycidyl dimethacrylate (Bis-GMA) based resin. In the present study, the effectiveness of the BABC for repair of segmental bone defects under load-bearing conditions was examined using a rabbit tibia model. Polymethylmethacrylate (PMMA) bone cement was used as a control. A 15-mm length of bone was resected from the middle of the shaft of the tibia, and the tibia was fixed by two Kirschner wires. The defects were replaced by cement. Each cement was used in 12 rabbits; six rabbits were sacrificed at 12 and 25 weeks after surgery, and the tibia containing the bone cement was excised and tension tested. At both the intervals studied, the failure loads of the BABC were significantly higher than those of the PMMA cement. The BABC was in direct contact with bone, whereas soft tissue was observed between the cement and bone in all PMMA cement specimens. Results indicated that the BABC was useful as a bone substitute under load-bearing conditions.