Preparation and compressive strength of alpha-tricalcium phosphate/gelatin gel composite cement.

A novel alpha-tricalcium phosphate (TCP) and gelatin gel composite cement was prepared, and the effects of gelatin content, liquid/powder ratio, setting time, and additives (rod-like hydroxyapatite and CaTiO3 particles) on the microstructure and compressive strength of the setting product were investigated. Addition of gelatin gel to alpha-TCP cement resulted in the formation of a porous solid possessing pores of 20-100 microm in diameter whose pore diameter increased with increasing gelatin gel content. The compressive strength of alpha-TCP cement after 1 week increased from 9.0 to 14.1 MPa with increasing gelatin gel content up to 5 wt % and thereafter decreased. The compressive strength of the cement containing 5 wt % gelatin gel increased with time up to 35 MPa after 1 month whereas without gelatin gel it was approximately 20 MPa. Dispersion of 5 wt % of rod-like hydroxyapatite and CaTiO3 powders with alpha-TCP cement containing 5 wt % gelatin gel increased the compressive strength after 1 week from 14.1 to 31.3 and 34.8 MPa, respectively.     

Material characterization and in vivo behavior of silicon substituted alpha-tricalcium phosphate cement

The possibility and biological effects of substituting silicon in alpha-tricalcium phosphate (alpha-TCP) by way of solid-state reaction have been evaluated. alpha-TCP powders with varying substitution amounts (1 and 5 mol % Ca2SiO4) were synthesized by reacting mixtures of CaCO3, Ca2P2O7, and SiO2, at a rate of 4 degrees C(min)(-1) to 1100 degrees C, left to dwell for 2 h and then heated to 1325 degrees C at 4 degrees C(min)(-1) and left to dwell for a period of 4 h. The powders were then rapidly quenched in air. Si incorporation could be verified by X-ray diffraction analysis, indicating an increase of the lattice volume with increasing Si content from 4284.1(8) to 4334(1) A3 for pure alpha-TCP and alpha-Si5%TCP, respectively. The hydrolysis of milled alpha-SiTCP powders was monitored by isothermal calorimetry, and the compressive strength of set cements was tested. The results showed changes in speed and amount of heat released during reactivity tests and a decrease in mechanical strength (60, 50, and 5 MPa) with increasing Si content. In vitro bioactivity of the set cements after soaking in simulated body fluid for 4 weeks was also tested. The formation of a bonelike apatite layer on the surface of the set cements could be observed and was thickest for 1%Si (20 microm). These results were in good agreement with the in vivo studies performed, which showed strong evidence that the cement containing 1% silicon doped alpha-TCP enhanced mesenchymal cell differentiation and increased osteoblast activity compared with alpha-TCP.     

Combined effect of strontium and pyrophosphate on the properties of brushite cements

In this study we report the synthesis of strontium-containing brushite cement with good cohesion and a diametral tensile strength (DTS) of 5 MPa. The cement powder, composed of β-tricalcium phosphate (β-TCP) and monocalcium phosphate, was adjusted by different concentrations of strontium and pyrophosphate ions. The cement liquid phase was 2 M phosphoric acid solution. The cement cohesion and mechanical properties were measured after being aged in water for 24 h at 37 °C. It was found that at low concentration both strontium and pyrophosphate ions inhibit the cement setting reaction. However, the final setting time was significantly reduced when SrCl₂ increased from 5 to 10 wt.% at pyrophosphate concentrations equal to or higher than 2.16 wt.%. The incorporation of strontium ions did not increase the DTS of brushite cements significantly. In contrast, the addition of pyrophosphate ions did increase the DTS of brushite cements significantly. When both ions were added simultaneously, the brushite cement with a Sr²⁺ content of 5 wt.% had the highest DTS value. Nevertheless, the DTS values of Sr-containing cements were significantly reduced if the pyrophosphate concentration was higher than 2.16 wt.%. The Sr²⁺ ions had a negative effect on brushite cement cohesion, although the solid weight loss started to decrease at Sr²⁺ concentrations higher than 5 wt.%.     

硅酸钙-磷酸盐复合骨水泥的制备及其性能研究

分别以α-磷酸三钙（α—TCP）、磷酸四钙（TTCP）为基本原料，添加羟基磷灰石（HAP）、磷酸氢钙（DCPD）、碳酸钙（CaCO2）、氧化钙（CaO）等其它辅料，并与一定量的无定形硅酸钙（CaSiO3）进行复合，确定了钙磷比均为1．50的六种骨水泥配方，对其基本性能进行了研究。对固化骨水泥样品进行了Ringer’S模拟液浸泡实验，研究了浸泡液pH值、样品的抗压强度随浸泡时间的变化。结果表明：调和液0．25MK2HPO4／KH2PO4和无定形CaSiO3对骨水泥有促凝作用，缩短骨水泥的终凝时间，其中初凝时间为4～5．5min，终凝时间为18～19．5min；同时添加适量无定形CaSiO3可以显著提高骨水泥的抗压强度，其中添加适量无定形CaSiO3的以α—TCP为主要原料的骨水泥Ringer’s模拟液浸泡两周后抗压强度可达45．3MPa。     

Immersion behavior of gelatin-containing calcium phosphate cement

Calcium phosphate cements (CPCs) have many favorable properties that support their clinical use as bone defect repair. However, it is difficult to deliver to the required site and hard to compact adequately due to inherently low ductility of ceramics. The aim of this study focused on the effect of the gelatin content on properties of CPCs. The diametral tensile strength, morphology, and weight loss of gelatin cements were evaluated after immersion in physiological solution, in addition to setting time. The results indicated that the setting time significantly increased with increasing gelatin amount. The 2 wt.% gelatin could make CPCs attain the maximum strength value of 2.1 MPa at 15-day immersion, while 1.6 MPa for the cement without gelatin. It is concluded that the presence of gelatin improved mechanical properties of CPCs; in particular, 2 wt.% gelatin. CPCs containing 2 wt.% gelatin hardened in an acceptable time recommended for clinical applications.     

α-磷酸三钙/HA晶须/羧甲基壳聚糖-明胶复合增强多孔骨水泥的制备研究

为研究羟基磷灰石(HA)晶须和羧甲基壳聚糖-明胶(CMC-Gel)对多孔磷酸钙骨水泥(CPC)力学性能的影响,将α-磷酸三钙(α-TCP)粉、HA晶须和致孔剂L-谷氨酸钠按一定的质量比进行混合,加入调和液制备成α-TCP/HA晶须复合多孔骨水泥,然后将其浸润到一系列不同CMC和Gel质量比的溶液中以制备α-TCP/HA晶须/CMC-Gel复合增强多孔骨水泥,对其进行抗压强度测试和扫描电镜观察。结果显示,当HA晶须含量为4%,未添加CMC和Gel时,α-TCP/HA晶须复合多孔骨水泥的抗压强度达到2.57MPa,与未复合HA晶须的骨水泥相比提高了81%;当CMC和Gel的质量比为50∶50时,α-TCP/HA晶须/CMC-Gel复合多孔骨水泥的抗压强度达到最大值3.34MPa,与单纯的多孔α-TCP骨水泥相比提高了135%,同时韧性也有较大改善。     

A novel strontium(II)-modified calcium phosphate bone cement stimulates human-bone-marrow-derived mesenchymal stem cell proliferation and osteogenic differentiation in vitro

In the present study, the in vitro effects of novel strontium-modified calcium phosphate bone cements (SrCPCs), prepared using two different approaches on human-bone-marrow-derived mesenchymal stem cells (hMSCs), were evaluated. Strontium ions, known to stimulate bone formation and therefore already used in systemic osteoporosis therapy, were incorporated into a hydroxyapatite-forming calcium phosphate bone cement via two simple approaches: incorporation of strontium carbonate crystals and substitution of Ca²⁺ by Sr²⁺ ions during cement setting. All modified cements released 0.03–0.07 mM Sr²⁺ under in vitro conditions, concentrations that were shown not to impair the proliferation or osteogenic differentiation of hMSCs. Furthermore, strontium modification led to a reduced medium acidification and Ca²⁺ depletion in comparison to the standard calcium phosphate cement. In indirect and direct cell culture experiments with the novel SrCPCs significantly enhanced cell proliferation and differentiation were observed. In conclusion, the SrCPCs described here could be beneficial for the local treatment of defects, especially in the osteoporotic bone.     

Effect of added gelatin on the properties of calcium phosphate cement

This study investigates the effect of gelatin on the setting time, compressive strength, phase evolution and microstructure of calcium phosphate cement. The composite cement powder (about 18 wt% gelatin, and 82 wt% alpha-tricalcium phosphate) was prepared from the solid compound obtained by casting a gelatin aqueous solution containing alpha-tricalcium phosphate. 5 wt% of CaHPO(4) x 2H(2)O were added to the powder before mixing with the liquid phase. Two cement formulations were prepared using two different liquid/powder ratios, and their properties compared with those of control samples, prepared without gelatin. The final setting time increases from 10 min to more than 45 min when the L/P ratio increases from 0.3 to 0.4 ml/g. The presence of gelatin accelerates the setting reaction, and improves the mechanical properties of the cements. The compressive strength increases with the setting reaction up to 10.7-14.0 MPa for the gelatin cements, whereas the control samples exhibit much lower values. The improved mechanical properties of the composite cements with respect to the controls can be related to their reduced total porosity and more compact microstructure.     

Rheological enhancement of mechanically activated alpha-tricalcium phosphate cements

Most biocements are two- or three-component acid-based systems with large differences in the component particle sizes, which occurs by virtue of the differing processing routes. This work aimed to improve injectability and strength of a single reactive component cement, that is, mechanically activated alpha-tricalcium phosphate (TCP)-based cement by adding 13-33 wt % of several fine-particle-sized (d(50) of 0.5-1.1 microm) fillers [dicalcium phosphate anhydrous (DCPA), titanium dioxide (TiO(2)), and calcium carbonate] to the monomodal alpha-TCP matrix (d(50) = 9.8 microm). A high zeta-potential was measured for all particles in trisodium citrate solution. The fraction of alpha-TCP cement "injected" through an 800-microm hypodermic needle was found to be only 35% at a powder-to-liquid ratio of 3.5 g/mL. In contrast, the use of fillers decreased cement viscosity to a point, where complete injectability could be obtained. Mechanistically, these additives disrupted alpha-TCP particle packing yet decreased the interparticle spacing by a factor of approximately 5.5 such that the electrostatic repulsion effect was enhanced. A strength improvement was found when DCPA and TiO(2) were used as fillers despite the lower degree of conversion of these cements. Compressive strengths of precompacted cement samples increased from 70 MPa for unfilled alpha-TCP cement to 140 (110) MPa for 23 wt % DCPA (or TiO(2)) fillers as a result of porosity reduction. Strength improvement for more clinically relevant uncompacted cements was achieved by higher powder-to-liquid ratio mixes for filled cements such that maximum strengths of 90 MPa were obtained for 23 wt % DCPA filler compared with 50 MPa for single-component alpha-TCP cement.     

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.     

Release profile of antimicrobial agents from alpha-tricalcium phosphate cement.

A new method for treating carious dentine with alpha-tricalcium phosphate (alpha-TCP) dental cement containing antimicrobial agents has been recently introduced. However, the release behavior of antimicrobial agents from this cement has not yet been clarified. The aim of this study is therefore to examine the release profile of the antimicrobial agents from the alpha-TCP cement. Three kinds of antimicrobial agents (metronidazole, cefaclor and ciprofloxacin) were added to two commercially available alpha-TCP cements (new apatite liner type I and type II). The set cements were then immersed in water at 37 degrees C and the released antimicrobial agents and Ca ion were determined at regular intervals for three months. In addition, scanning electron microscopic observations were conducted before and after immersion for three months. The release profile of the cements containing antimicrobial agents varied depending on the types of antimicrobial agents. The incorporation of antimicrobial agents affected the setting reaction of the cements. The release behavior of the drugs also varied depending on the types of the cements. The differences in the release profile between type I and type II cements reflected the structures and compositions of their matrices.     

In vitro assessment of poly(methylmethacrylate)-based bone cement containing magnetite nanoparticles for hyperthermia treatment of bone tumor

Poly(methylmethacrylate) (PMMA)-based cements containing magnetite (C-PMMA/Fe(3) O(4) ) is useful in hyperthermia treatment for bone tumor. We have prepared C-PMMA/Fe(3) O(4) by incorporating Fe(3) O(4) powders of different diameters (means of 300, 35, and 11 nm) into the polymerization reaction of methyl methacrylate monomer to develop a new bone cement with high heating efficiencies in alternating current (AC) magnetic fields. Further, we have investigated the in vitro heating capability of the cements in different AC magnetic fields. The mechanical strength and biocompatibility of the resultant cements were also assessed. Their heat generation strongly depends on the magnetite nanoparticle sizes and applied magnetic fields. The cement containing Fe(3) O(4) with mean diameter around 35 nm exhibited the highest heating capability in AC magnetic fields of 120 and 300 Oe at 100 kHz while that with mean diameter around 11 nm exhibited optimum heating capability in AC magnetic fields of 40 Oe at 600 kHz. The incorporation of Fe(3) O(4) into cement-30 wt % of the total amount of cement-did not significantly change the compressive strength of cement, and the proliferation of rat fibroblast Rat-1 cells on cement discs was not inhibited. Our investigations are useful for designing new PMMA/Fe(3) O(4) bone cement with high heating efficiencies and biocompatibilities for bone tumor treatments. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2537-2545, 2012.     

Biological and mechanical properties of PMMA-based bioactive bone cements

We reported previously that a bioactive PMMA-based cement was obtained by using a dry method of silanation of apatite-wollastonite glass ceramic (AW-GC) particles, and using high molecular weight PMMA particles. But handling and mechanical properties of the cement were poor (Mousa et al., J Biomed Mater Res 1999;47:336-44). In the present study, we investigated the effect of the characteristics of PMMA powder on the cement. Different cements containing different PMMA powders (CMW1, Surgical Simplex, Palacos-R and other two types of PMMA powders with Mw 270,000 and 1,200,000) and AW-GC filler in 70 wt% ratio except Palacos-R (abbreviated as B-CMW1 and B-Surg Simp, B-Palacos 50 [50 wt% AW-GC filler] and B-Palacos 70 [70 wt% AW-GC filler], B-270 and B-1200) were made. Dough and setting times of B-CMW1, B-Surg Simp B-270 and B-1200 were similar to the commercial CMW1 cement which did not contain bioactive powder (C-CMW1), but B-palacos which contained large PMMA beads with high Mw had delayed setting time. B-270 had the highest bending strength among the tested cements. After 4 and 8 weeks of implantation in the medullary canals of rat tibiae, the bone-cement interface was examined using SEM. The affinity index of B-1200 was significantly higher than the other types of cements. B-270 showed good combination of handling properties, high mechanical properties and showed higher bioactivity with minimal soft tissue interposition between bone and cement compared with commercial PMMA bone cement. This may increase the strength of the bone-cement interface and increase the longevity of cemented arthroplasties.     

Physico-chemical-mechanical and in vitro biological properties of calcium phosphate cements with doped amorphous calcium phosphates

Calcium phosphate cements (CPCs) are successfully used as bone substitutes in dentistry and orthopaedic applications. This study investigated the physico-chemical-mechanical properties of and in vitro biological properties (cell response) of CPCs prepared with amorphous calcium carbonate phosphate (ACCP) doped with magnesium (ACCP-Mg), zinc (ACCp-Zn) or fluoride (ACCP-F) ions. The experimental CPC consisted of alpha-TCP, doped ACCP, and MPCM powders as matrix and biphasic calcium phosphate (BCP) granules. X-ray diffraction analysis showed that the matrix converted to apatite with poor crystallinity (reflecting small crystal size) after setting for 24 h, while BCP remained apparently unchanged. Cements with ACCP-F (F-CPC) had shorter setting times and greater compressive strength compared to cements with ACCP-Mg (Mg-CPC) or ACCP-Zn (Zn-CPC). Scanning electron microscopy (SEM) showed that crystals set on Mg-CPC and Zn-CPC were smaller compared to those on F-CPC. The total porosity of Mg-CPC was greater compared to Zn-CPC or F-CPC. Osteoblast-like cells, MC3T3-E1, remained viable and maintained their ability to express alkaline phosphatase in contact with the CPCs with doped ACCPs.     

Energy dispersive X-ray diffraction study of phase development during hardening of calcium phosphate bone cements with addition of chitosan

The aim of this work was to study the phase transformation during the setting reaction of two calcium phosphate bone cements based on either alpha tricalcium phosphate (alpha-TCP) or tetracalcium phosphate (TetCP) initial solid phase, and a magnesium carbonate-phosphoric acid solution as the hardening liquid. Low molecular weight (38.2 kDa) chitosan was used to retard the cement's setting reaction. To follow the kinetics of the phase development, an energy dispersive X-ray diffraction technique was applied. This technique allowed the collection of diffraction patterns from the cement pastes in situ starting from 1 min of the setting process. In the case of the TetCP-based cement, the appearance and evolution of an intermediate phase was detected.     

Modulation of porosity in apatitic cements by the use of alpha-tricalcium phosphate-calcium sulphate dihydrate mixtures

Calcium phosphate bone cements are injectable biomaterials that are being used in dental and orthopaedic applications through minimally invasive surgery techniques. Nowadays, apatitic bone cements based on alpha-tricalcium phosphate (alpha-TCP) are of special interest due to their self-setting behaviour when mixed with an aqueous liquid phase. In this study, a new method to improve osteointegration of alpha-TCP-based cements is presented. This method consists in the modification of the cement's powder phase with different amounts of calcium sulphate dihydrate (CSD). The resulting hardening properties of the new biphasic cements are a combination between the progressive hardening due to the main alpha-TCP reactant and the progressive dissolution of the CSD phase, which render a porous material. It was observed that the maximum compressive strength of Biocement-H (45 MPa) decreased as the amount of CSD increased in the cement powder mixture ( approximately 30 MPa for 25 wt% of CSD). It was also observed that after complete dissolution of the CSD phase a porous apatitic structure appears with a mechanical compressive strength suitable for cancellous bone applications (10 MPa).     

Evaluation of apatite ceramics containing alpha-tricalcium phosphate by immersion in simulated body fluid

The purpose of this study was to estimate the availability of alpha-tricalcium phosphate (alpha-TCP) on/in hydroxyapatite (HAP) ceramics for bioactivity as bone-substitute materials by immersion in a simulated body fluid (SBF; Hanks' solution) containing ion concentrations similar to those in human blood plasma. Two alpha-TCP-surface-modified HAP and alpha-TCP-HAP composite materials were prepared by orthophosphoric acid treatment of sintered HAP and controlling the crystal phases of calcium phosphate cement, respectively. After immersion in SBF, the sintered HAP modified on the surface in an approximately 0.2 microm alpha-TCP layer was more effective for the precipitation of carbonated apatites than an approximately 2 microm alpha-TCP layer and HAP-only layer. In the calcium phosphate cements consisting of HAP and alpha-TCP phases, after immersion for 1 week, the specimens precipitated large amounts of apatites having alpha-TCP contents of approximately 25% and 50% in the cement. The results of immersion tests imply the possibility that the alpha-TCP on/in HAP ceramics may be a bioactive agent for bone-substituting HAP materials.     

Characterization of a novel calcium phosphate/sulphate bone cement

Apatitic cements have shown excellent biocompatibility and adequate mechanical properties but have slow resorption in the human body. To assure that new bone tissue grows into the bone defect, a certain porosity is necessary although hard to achieve in injectable cements with suitable mechanical properties. An attempt was made by mixing alpha-tricalcium phosphate (alpha-TCP), calcium sulphate hemihydrate (CSH) and an aqueous solution containing 2.5 wt% of Na(2)HPO(4). The aim was to obtain a material containing two phases: a) one apatitic phase (calcium-deficient hydroxyapatite; CDHA) and b) one resorbable phase (calcium sulphate dihydrate; CSD). alpha-TCP and CSH mixtures were produced at relative intervals of 20 wt%. The liquid-to-powder (L/P) ratio to obtain a paste was 0.32 mLg(-1). The highest compressive strength (34 MPa) was obtained for the pure alpha-TCP sample. The strength was, in a first approximation, directly correlated to the weight proportions of the powders. X-ray diffraction analysis showed that the relative intensity for CDHA increased linearly, and the one for CSD decreased exponentially, when the amount of alpha-TCP increased. Thus, CSH ceased to transform to CSD when the amount of alpha-TCP increased. Observations in environmental scanning electron microscopy confirmed the X-ray diffraction results. CSH-crystals (100 microm) were embedded in the HA-matrix permitting gradual porosity in the material when resorbed.     

碳纤维增强α-磷酸三钙骨水泥的研究

为提高α-磷酸三钙（α—TCP）骨水泥的强度及降低其脆性，将表面改性后的碳纤维（CF）与α—TCP粉复合，制备成α—TCP／CF复合增强骨水泥。通过Ringer’s体液浸泡观察骨水泥快速结晶自固化能力，运用扫描电子显微镜（SEM）及抗压强度测试仪对复合材料浸泡后试样进行断面显微结构分析及抗压强度测试。结果显示，α—TCP骨水泥块浸泡5d后即转化生成片状羟基磷灰石晶体；适量的碳纤维在骨水泥基体中分布均匀，与基体结合性好，可得到抗压强度增强的骨修复材料；当碳纤维的加入重量百分数为0．5％时，复合材料抗压强度达到46．7MPa，比未增强的α—TCP材料提高了22％。     

Contact killing antimicrobial acrylic bone cements: preparation and characterization

Novel antimicrobial poly(methyl methacrylate) (PMMA)-based bone cement was synthesized by co-polymerizing PMMA/MMA with various percentages of quaternary amine dimethacrylate (QADMA) by free radical bulk polymerization technique at room temperature using benzoyl peroxide and N,N-dimethyl-p-toulidine (DMPT) as a redox initiator. The modified bone cement was characterized by FT-IR and 1H-NMR spectral studies. The thermal and physical properties of the bone cements of varying composition of QADMA were evaluated by thermogravimetric analysis (TGA), differential calorimetry (DSC) and contact angle measurements. Peak exothermic temperature was observed to decrease, while setting time increased with increase in QADMA content in the bone cement formulations. The antibacterial activity of the synthesized bone cement containing quaternary amine dimethacrylate against Escherichia coli and Staphylococcus aureus was studied by zone of inhibition, colony count method and scanning electron microscopy (SEM). QADMA containing acrylic bone cement showed a broad spectrum of contact killing antimicrobial properties. Retention of E. coli onto the surface of PMMA bone cement was observed, whereas there was complete prevention of retention of E. coli onto the modified PMMA bone cement with 15% QADMA. The studies were compared with the acrylic bone cement synthesized using 15% N-vinyl-2-pyrrolidone (NVP) in place of QADMA to which iodine was added as an antimicrobial agent during co-polymerization.