氧化石墨烯对磷酸钙骨水泥的水化行为的影响

将氧化石墨烯(GO)分散液作为固化液,研究了该固化液对磷酸钙骨水泥(CPC)的水化行为的影响。利用维卡仪、万能压力试验机和热导式等温量热仪等研究了GO浓度对CPC骨水泥的凝结时间、抗压强度和水化行为的影响。利用X射线衍射和扫描电子显微镜等技术研究了GO浓度对CPC骨水泥固化体的晶相组成和断面形貌的影响。研究结果表明,固化液中加入GO,对骨水泥的断面形貌和水化产物均有影响,同时可以使CPC骨水泥的凝结时间由(36±4)min大幅度延长到(67±2)min,抗压强度由(20.1±1.7)MPa增加到(25.6±2.7)MPa。     

可注射磷酸钙骨水泥复合材料研究进展

研制既具有多孔结构又具有足够力学强度的磷酸钙骨水泥材料是当前骨修复材料研究的热点之一。报道了研制的磷酸钙骨水泥复合材料,在植入初期具有较高的力学强度,植入后可渐渐降解成孔,为骨修复材料的研究提供了新的方法和途径。磷酸钙骨水泥复合材料以磷酸钙骨水泥为基体,在基体中加入具有生物降解性的微球形成复合材料,保证了复合材料植入初期有足够力学强度为新生组织提供支撑,防止自身的坍塌,而具有生物降解性微球的降解速度比磷酸钙骨水泥的固化体快,随着微球的降解在磷酸钙骨水泥基体中就会产生很多三维孔隙,利于细胞粘附生长,血管和神经长入,以及营养成分的渗入和代谢产物排出。这种结构设计使可体内降解成孔的磷酸钙骨水泥既具有足够力学强度又具有多孔结构,还可以通过改变不同材料的比例来调节复合材料的初始力学强度和降解速度。目前已研制成功了壳聚糖微球/磷酸钙骨水泥复合材料、聚羟基丁酸—戊酸酯(PHBV)/磷酸钙骨水泥复合材料,其凝固时间为10～15min,抗压强度达到30～40MPa,孔隙率70%～80%,孔径分布为100～300μm,并对复合材料的降解性、细胞相容性和动物体内植入试验进行了研究,表明所研制的材料具有良好的生物相容性,可降解性和成...     

磷酸钙骨水泥负载庆大霉素的制备与性能

制备了庆大霉素、磷酸钙骨水泥药物缓释体系,研究了药物缓释效果及载入庆大霉素对骨水泥组成、结构与性能的影响.结果表明,庆大霉素、磷酸钙骨水泥体系具有良好的药物缓释效果;随着庆大霉素的载入,骨水泥的凝结时间延长,但当载入量达到5%时,骨水泥的凝结时间又缩短至15 min,继续增大药物含量,凝结时间又略有延长.低载药量(1%)时骨水泥的抗压强度有所提高,但再继续增大载药量,体系的抗压强度又逐渐下降.庆大霉素的加入对骨水泥的最终水化产物没有明显影响,水化产物都是弱结晶的羟基磷灰石.庆大霉素的载入量为3%～5%时,庆大霉素/磷酸钙骨水泥缓释体系具有最佳的综合性能.     

β-TCP可注射骨水泥的制备工艺及性能研究

以自制β-TCP作为CPC固相粉体,以壳聚糖、柠檬酸、聚乙烯醇按一定的比例配置成溶液作为液相,设计正交试验以简化实验,从凝固时间和抗压强度两方面来确定该体系CPC的最佳配比,制备可满足临床需要的可注射磷酸钙骨水泥。并分析了各个组分对凝固时间和抗压强度影响。此外,通过细胞培养实验评价了最优条件下骨水泥的生物相容性。     

含盐酸四环素α-TCP骨水泥的理化性能

对含有盐酸四环素的α-TCP骨水泥的理化性能进行了研究。盐酸四环素吸附和同钙离子螯合而结合到磷酸钙晶体表面,从而对磷酸钙骨水泥的水化过程产生影响。研究结果表明,盐酸四环素的加入一定程度上延长了骨水泥的凝结时间．但XRD分析显示并不影响α-TCP的最终的转化;同时改变了骨水泥固化体的晶体形貌和微结构,使形成的羟基磷灰石晶体由原来发散的针状晶转变为相互交织的条状和层状晶,这种晶体形貌的改变在一定盐酸四环素含量的条件下明显提高了骨水泥的抗压强度。     

柠檬酸浓度对硼酸盐玻璃骨水泥性能的影响

以壳聚糖-甘油磷酸钠-柠檬酸溶液为液相, 制备了一种新型可注射的硼酸盐玻璃骨水泥, 通过维卡仪、万能试验机、XRD、FTIR、SEM-EDS等探究了液相中柠檬酸浓度(0.1, 0.2和0.4 g/mL)对硼酸盐玻璃骨水泥性能的影响。结果表明: 柠檬酸浓度显著影响骨水泥的凝结时间和可注射性。柠檬酸浓度为0.2 g/mL时获得的骨水泥的凝结时间最短, 为(16±0.5) min; 可注射性最好, 接近100%。骨水泥压缩强度随柠檬酸浓度增大而增强, 最大可达(26.7±1.9) MPa。SEM照片显示骨水泥中生成了许多纳米微粒。XRD、FTIR和EDS等结果证明, 这些纳米微粒主要是硼酸盐、磷酸盐和柠檬酸盐等物质, 而且柠檬酸浓度能够影响骨水泥中硼酸盐晶体的形成。此外, 柠檬酸能够加速玻璃颗粒在磷酸钠盐缓冲液中的降解速率。     

磷酸钙骨水泥的制备及性能

磷酸钙骨水泥是一种新型的骨修复材料,具有良好的生物相容性。针对其机械性能不是很高的弱点,本文研究了钙磷摩尔比、固化液组成、模拟体液浸泡等制备条件对骨水泥力学性能的影响。结果表明,钙磷比为1．67,固化液为模拟体液,浸泡3天可以得到强度相对较高的水化产物。     

磷酸钙/纤维蛋白胶复合支架材料的结构及力学性能分析

用可吸收磷酸钙骨水泥和纤维蛋白胶按一定比例体外构建复合支架材料,通过XRD、SEM、抗压实验和空隙率测试等方法对其结构及力学性能进行分析.结果发现:由于加入纤维蛋白胶,复合支架材料在一定程度上延长了磷酸钙骨水泥的初凝时间,但并不影响磷酸钙骨水泥的终凝时间;同时,加入纤维蛋白胶改变了骨水泥固化体的微观结构,提高了骨水泥的抗压强度,其最大抗压强度达到14MPa,弹性模量在96.64～269.39MPa之间,空隙率为38.8%.与在同样条件下制备的磷酸钙骨水泥比较,复合支架材料的抗压强度增强了55.6%,而空隙率仅仅下降了6.9%;XRD分析显示,复合支架材料并不影响磷酸钙骨水泥的最终的转化,其结晶结构仍是羟基磷灰石结构,是更好的骨组织工程支架材料.     

磷酸钙骨水泥机械性能的研究

目前,磷酸钙骨水泥(CPC)的脆性大、强度低限制了其在很多承受应力部位或骨质薄弱部位的应用,提高骨水泥的机械性能是扩展骨水泥应用范围的重要方面.分别从CPC固体粉末的组成、原料的粒度、液固比与孔隙率、羟基磷灰石晶种的加入、固化液组成、有机无机复合、纤维增强等方面来综述提高骨水泥强度的研究.     

硫酸钙/磷酸三钙可控骨水泥的制备及性能研究

研究中,α-磷酸三钙(α-tricalcium phosphate,α-TCP)分别以0,5%,10%,15%,20%,25%的比例与α-半水硫酸钙(α-calcium sulfate hemihydrate,α-CSH)进行复合;分别以0.9%NaCl溶液、2.5%Na_2HPO_4溶液、7%柠檬酸(citric acid,CA)溶液以及2.5%Na_2HPO_4和7%CA(2.5%Na_2HPO_4/7%CA)混合溶液为4种固化液与固体粉末进行复合;对硫酸钙/磷酸三钙骨水泥(α-CSH/α-TCP)的可控性进行研究。实验对复合材料进行扫描电镜(scanning electron microscope,SEM)观察、X射线衍射(X-ray diffraction, XRD)分析、固化时间、力学性能和降解性能测试。探讨了加入α-TCP含量的改变对以α-CSH为基体的骨水泥性能的影响;另外,在α-CSH和α-TCP的含量一定时,讨论固化液对α-CSH/α-TCP性能的影响。结果表明在硫酸钙基骨水泥中添加平均粒径为0.21μm的α-TCP后,α-CSH/α-TCP的降解性能相较于纯的α-CSH基骨水泥得到改善。随着α-TCP含量的增加,固化时间延长,力学性能呈现逐渐减弱的趋势;当α-TCP含量为15%时,Na_2HPO_4和CA的加入可以延长α-CSH/α-TCP的凝固时间,但是以Na_2HPO_4为固化液的复合材料抗压强度明显高于α-CSH/α-TCP与其它几种固化液的复合材料。α-TCP的添加,以及不同的固化液在一定程度可对复合骨水泥的力学性能、凝固时间和降解速率进行调节,为骨修复材料的临床应用提供实验依据。     

Preparation and properties of calcium phosphate cements incorporated gelatin microspheres and calcium sulfate dihydrate as controlled local drug delivery system

To develop high macroporous and degradable bone cements which can be used as the substitute of bone repairing and drug carriers, cross-linked gelatin microspheres (GMs) and calcium sulfate dihydrate (CSD) powder were incorporated into calcium phosphate bone cement (CPC) to induce macropores, adjust drug release and control setting time of α-TCP–liquid mixtures after degradation of GMs and dissolution of CSD. In this study, CSD was introduced into CPC/10GMs composites to offset the prolonged setting time caused by the incorporation of GMs, and gentamicin sulphate (GS) was chosen as the model drug entrapped within the GMs. The effects of CSD amount on the cement properties, drug release ability and final macroporosity after GMs degradation were studied in comparison with CPC/GMs cements. The resulting cements presented reduced setting time and increased compressive strength as the content of CSD below 5 wt%. Sustained release of GS was obtained on at least 21 days, and release rates were found to be chiefly controlled by the GMs degradation rate. After 4 weeks of degradation study, the resulting composite cements appeared macroporous, degradable and suitable compressive strength, suggesting that they have potential as controlled local drug delivery system and for cancellous bone applications.     

Physicochemical properties and release characteristics of growth factor‐modified calcium phosphate bone cement

The addition of growth factors, such as recombinant human transforming growth factor‐β1 (rhTGF‐β1) to calcium phosphate cements (CPCs) may improve bone regeneration. Previously we have shown that the differentiation of pre‐osteoblastic cells from adult rat long bones was stimulated by rhTGF‐β1 in CPC. CPC that was intermixed with rhTGF‐β1 and then applied in rat calvarial defects enhanced bone growth around the cement and increased the degradation of the cement. It is still unknown however whether the addition of rhTGF‐β1 changes the material properties of the CPC, and what the release characteristics are of rhTGF‐β1 from the CPC. We therefore determined here the release of rhTGF‐β1 in vitro from the cement pellets as implanted in the rat calvariae. The possible intervening effects of rhTGF‐β1‐intermixing on clinical compliance of CPC were studied by assessing its compressive strength and setting time, as well as crystallinity, calcium to phosphorus ratio, porosity and microscopic structure. CPC was prepared by mixing calcium phosphate powder (58% α‐tricalcium‐phosphate, 25% dicalcium‐phosphate anhydrous, 8.5% calcium‐carbonate and 8.5% hydroxyapatite), with liquid (3 g/ml). The liquid for standard CPC consisted of water with 4% sodium hydrogen phosphate, while the liquid for modified CPC, was mixed with an equal amount of 4 mM hydrochloride with 0.2% bovine serum albumin. The hydrochloride liquid contained the rhTGF‐β1 in different concentrations for the release experiments. Most of the incorporated rhTGF‐β1 in the cement pellets was released within the first 48 hr. Approximately 0.5% rhTGF‐β1 (intermixed at 100 ng to 2.5 mg/g CPC) was released within the first 4 hr increasing to 1% after 48 hr. rhTGF‐β1 release continued at 0.1% up to at least 8 weeks. Modification of CPC slightly increased the initial setting time at 20°C from 2.6 to 5 min, but did not affect the final setting time of the CPC at 20°C, nor the initial and final setting time at 37°C. The compressive strength was increased from 18 MPa (standard CPC) to 28 MPa (modified CPC) only at 4 hr after mixing. The compressive strength diminished in the modified CPC between 24 hr and 8 weeks from 55 to 25 MPa. X‐ray diffraction revealed that both standard and modified CPC changed similarly from the basic components, alpha‐tri‐calcium phosphate and dicalcium phosphate anhydrous, into an apatite cement. The calcium to phosphorus ratio as determined by an electron microprobe did not differ for standard CPC and modified CPC. Standard and modified CPC became a dense and homogeneous structure after 24 hr, but the modified CPC contained more crystal plaques compared to the standard CPC, as observed by scanning electron microscopy (SEM). SEM and back scattered electron images revealed that after 8 weeks both cements showed an equally and uniform dense structure with microscopic pores (less than 1 μm). Both CPCs showed fewer crystal plaques at 8 weeks than at 24 hr. This study shows that the calcium phosphate cement was not severely changed by modification of the CPC for rhTGF‐β1. Clinical handling may be affected by the prolonged setting time of modified cement, but it is still within preferable limits. Compressive strength was for both standard and modified cements within the range of thin trabecular bone, and therefore both CPCs can withstand equal mechanical loading. The faster diminishing compressive strength of modified cement (from 24 hr to 8 weeks) likely results in early breakdown, and therefore might be favourable for bone regeneration. Together with our previous studies showing the beneficial effects of adding rhTGF‐β1 to CPC on bone regeneration, we conclude that the envisaged applications for CPC in bone defects are upgraded by intermixing of rhTGF‐β1. Therefore the combination of CPC with rhTGF‐β1 forms a promising synthetic bone graft.     

磷酸钙/BMP复合生物活性骨水泥水化性能及诱导成骨特性研究

采用微细α-磷酸三钙(α-TCP)粉料、辅助料与冻干牛骨形态发生蛋白(BMP)预先固相混合制备了新型磷酸钙(CPC)/BMP复合生物骨水泥.通过水化、凝固性能研究优化了配料成分、调和液和促凝剂组成;通过大鼠肌袋种植实验研究了骨水泥的异位成骨性能.结果表明:以α-TCP:CaHPO₄:CaO(0.95:0.025:0.025)为固相配料,以0.25mol/LNaH₂PO₄/Na₂HPO₄混合液([P]_T=0.5mol/L)作为调合液可制备性能优异的骨水泥材料,骨水泥初凝时间为6min,终凝时间为30min,固化强度达33MPa,达到临床手术的要求;α-TCP粉料粒度对骨水泥凝固性能影响显著,实验选用α-TCP粉料粒径d₅₀为1.3μm;骨水泥在Hank’s溶液中浸泡5天抗压强度可达最大值;骨水泥块经浸泡后内部生成针状羟基磷灰石晶体的网状结构.新型CPC/BMP复合骨水泥异位成骨作用明显,4周即能快速形成板层骨结构,证明该新型复合材料具有较强的诱导成骨活性.该生物活性骨水泥复合材料可望成为一类新型组织工程骨修复材料.     

Dual setting α-tricalcium phosphate cements

An extension of the application of calcium phosphate cements (CPC) to load-bearing defects, e.g. in vertebroplasty, would require less brittle cements with an increased fracture toughness. Here we report the modification of CPC made of alpha-tricalcium phosphate (α-TCP) with 2-hydroxyethylmethacrylate (HEMA), which is polymerised during setting to obtain a mechanically stable polymer-ceramic composite with interpenetrating organic and inorganic networks. The cement liquid was modified by the addition of 30–70 % HEMA and ammoniumpersulfate/tetramethylethylendiamine as initiator. Modification of α-TCP cement paste with HEMA decreased the setting time from 14 min to 3–8 min depending on the initiator concentration. The 4-point bending strength was increased from 9 MPa to more than 14 MPa when using 50 % HEMA, while the bending modulus decreased from 18 GPa to approx. 4 GPa. The addition of ≥50 % HEMA reduced the brittle fracture behaviour of the cements and resulted in an increase of the work of fracture by more than an order of magnitude. X-ray diffraction analyses revealed that the degree of transformation of α-TCP to calcium deficient hydroxyapatite was lower for polymer modified cements (82 % for polymer free cement and 55 % for 70 % HEMA) after 24 h setting, while the polymerisation of HEMA in the cement liquid was quantitative according to FT-IR spectroscopy. This work demonstrated the feasibility of producing fracture resistant dual-setting calcium phosphate cements by adding water soluble polymerisable monomers to the liquid cement phase, which may be suitable for an application in load-bearing bone defects.     

Increase of the final setting time of brushite cements by using chondroitin 4-sulfate and silica gel

Chondroitin 4-sulfate (C4S) is a bioactive glycosaminoglycan with inductive properties in bone and tissue regeneration. Dicalcium phosphate dehydrate cements (known as brushite) are biocompatible and resorbable materials used in bone and dental surgery. In this study we analyzed the effect of C4S on the setting of a calcium phosphate cement and the properties of the resulting material. Brushite based cement powder was synthesised by mixing monocalcium phosphate with β-tricalcium phosphate and sodium pyrophosphate. When the concentration of C4S, in the liquid added to the cement powder, was between 1 and 8% the cement final setting time increases. Furthermore, the cement diametral tensile strength remains unaffected when solutions with concentrations of C4S below 5% were used, but decreases at higher C4S concentrations. Calorimetric analysis showed that the cements prepared with C4S alone and in combination with silica gel have a greater content of hydrated water. We concluded from our study that the addition of small amounts of C4S increases the cement setting time without affecting its diametral tensile strength and at the same time improves the cement’s hydrophilicity.     

抗水型钙磷水泥生物活性骨修复材料研究

采用纤维素作为添加剂、以非水相溶剂作为固化液, 研究了一种抗水型磷酸钙骨水泥生物活性骨修复材料. 对其抗水性能、理化性能、水化产物及生物相容性进行了研究. 结果表明: 该骨水泥可任意塑形, 也可用针管注射成形, 抗水性能优良, 添加剂纤维素的加入, 对骨水泥的凝结时间、抗压强度及最后的转化产物没有明显影响. 培养细胞在材料表面粘附铺展且增殖良好, 初步表明材料有较好的生物相容性. 该材料有望用于骨缺损填充及椎体成形等微创手术.     

Synthesis of bioactive PMMA bone cement via modification with methacryloxypropyltri- methoxysilane and calcium acetate

Bone cement consisting of polymethylmethacrylate (PMMA) powder and methylmethacrylate (MMA) liquid is clinically used for fixation of implants such as artificial hip joints. However, it does not show bone-bonding ability, i.e., bioactivity. The lack of bioactivity would be one of factors which cause loosening between the cement and the implant. The present authors recently showed the potential of bioactive PMMA-based bone cement through modification with γ -methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. In this study, the effects of the kinds of PMMA powder on setting time, apatite formation and compressive strength were investigated in a simulated body fluid (Kokubo solution). The cement modified with calcium acetate calcined at 220 ^∘C could set within 15 min when the PMMA powder had an average molecular weight of 100,000 or less. The addition of calcium acetate calcined at 120 ^∘C in the PMMA powder required a much longer period for setting. The modified cements formed an apatite layer after soaking in the Kokubo solution within 1 day for cement starting from PMMA powder with a molecular weight of 100,000 or less. Compressive strengths of the modified cements were more than 70 MPa for cements starting from 100,000 and 56,000 in molecular weight. After soaking in Kokubo solution for 7 days, the modified cement consisting of PMMA powder of 100,000 in molecular weight showed a smaller decrease in compressive strength than that consisting of 56,000 in molecular weight. These results indicate that bioactive PMMA cement can be produced with appropriate setting time and mechanical strength when PMMA powders with a suitable molecular weight are used. Such a type of design of bioactive PMMA bone cement leads to a novel development of bioactive material for bone substitutes.     

Fabrication of mesoporous calcium silicate/calcium phosphate cement scaffolds with high mechanical strength by freeform fabrication system with micro-droplet jetting

In this study, we explored the feasibility of fabrication bioactive mesoporous calcium silicate/calcium phosphate cements (MCS/CPC) scaffolds with high mechanical strength by Freeform Fabrication System with Micro-Droplet Jetting. After preparation of ordered mesoporous calcium silicate (MCS) powder, ready-to-use MCS/CPC paste was formed by mixing calcium phosphate cement (CPC) powder and MCS powder with the binder polyvinyl alcohol (PVA) aqueous solution at a certain ratio of powder to liquid. MCS/CPC scaffolds with various architectures, pore sizes, and interconnectivity were then directly printed at room temperature using MCS/CPC paste. The mechanical strength, apatite formation, degradation rate, and cytocompatibility of the composite scaffolds were systematically investigated. The results showed that MCS/CPC paste exhibited outstanding printability to form MCS/CPC scaffolds. The hybrid MCS/CPC scaffolds with predefined pore size of 350 μm showed fast degradation rate, high mechanical strength, and good cytocompatibility. It was indicated that the hybrid MCS/CPC scaffolds might be a promising candidate for critical bone defect repair.     

Some factors controlling the injectability of calcium phosphate bone cements

The injectability of four calcium phosphate bone cements (CPBCs) was measured using a commercial disposable syringe. It varied considerably with the cement powder composition, with the liquid/powder ratio, with the time after starting the mixing of liquid and powder, with the accelerator concentration (% Na2HPO4), and with the ageing time of the cement powder which was prepared by milling. The injectability test could be used to determine accurately the dough time of CPBCs. Relations between the setting time and the cohesion time are discussed.     

The effect of modification of KH2PO4 hardening liquid with H3PO4 and chitosan on setting reactions and compressive strength of calcium phosphate cement

The setting processes and mechanical properties of tetracalcium phosphate (TTCP) -monetite cements with H₃PO₄ and chitosan modified KH₂PO₄ hardening liquid have been studied. From XRD phase analysis, it was found that brushite was created in the first stage of the setting process by the interaction between phosphate compounds in hardening liquids and TTCP. Calcium deficient hydroxyapatite was the final product of the hardening process. The orthophosphoric acid addition to KH₂PO₄ hardening liquid caused lowering resistance to disintegration and an increase in the setting times of cements which allows the possibility for their control. Cement with pure KH₂PO₄ hardening liquid was resistant to wash-out immediately after mixing. Chitosan addition to KH₂PO₄ + H₃PO₄ hardening liquid of an amount around 1 wt.% did not affect change of setting time or improvement of disintegration behaviour of cement. Compressive strengths were around 80–100 MPa in cements soaked in SBF without an chitosan addition and chitosan caused an approximately 15% decrease in compressive strength. The compressive strength of calcium phosphate cements is more influenced by the hydroxyapatite particle morphology than their crystallinity.