明胶溶胀行为对自固化多孔骨水泥性能和结构的影响

目的 研究明胶溶胀行为对多孔骨水泥性能和结构的影响。方法 在α-磷酸钙骨水泥体系中加入生物明胶，研究明胶对骨水泥水化产物、抗压强度和产物微结构所产生的影响。结果利用明胶的溶胀行为与水化过程中体系pH值变化的相关性，可制备具有大孔和微孔结构的骨水泥。结论加入明胶促进羟基磷灰石的成核，提高骨水泥的抗压强度。     

复合唑来膦酸磷酸钙骨水泥的力学性能测定

目的研究加入不同浓度的唑来膦酸对磷酸钙骨水泥体外凝结时间、抗压强度的影响。方法将唑来膦酸与磷酸钙骨水泥以不同质量比混合,制备力学性能测试标本,并分为A(空白对照)、B(含0.2%唑来膦酸)、C(含0.4%唑来膦酸)、D(含0.6%唑来膦酸)4组,每组6个标本。测定其凝结时间及抗压强度。结果随载药浓度的增加,复合磷酸钙骨水泥凝结时间逐渐延长,但各实验组凝结时间与空白对照组均无明显统计学差异(0.05)。B、C组抗压强度与A组之间无明显统计学差异(0.05),而D组与A组之间有统计学差异(=0.000)。结论三组中唑来膦酸的添加量对磷酸钙骨水泥凝结时间无明显影响,且各组凝结时间均满足临床应用标准。含0.2%和0.4%唑来膦酸对磷酸钙骨水泥抗压强度无明显影响,而含0.6%唑来膦酸可使磷酸钙骨水泥抗压强度明显降低。但三含量组的抗压强度均满足临床应用标准。     

利塞膦酸对硅酸钙骨水泥材料性能影响及体外释放机理的研究

目的探讨利塞膦酸对硅酸钙骨水泥材料性能的影响及其体外缓释的机理。方法将不同浓度的利塞膦酸(0.1%、0.5%和1.0%)与硅酸钙骨水泥粉末混合后进行水化反应,观察骨水泥固化时间及3天和7天后的抗压强度,并利用X射线衍射仪和Rietveld数字模拟精修方法定性与定量分析水化后骨水泥的相组成。同时,将固化后载药骨水泥样本放入磷酸盐缓冲液中,利用高效液相色谱仪检测利塞膦酸28天内的释放曲线。结果固化速度及3天和7天后力学强度均受到利塞膦酸的影响,且随着利塞膦酸含量的增加,固化速度减慢,力学性能下降。X射线衍射的定性分析与Rietveld定量分析表明,利塞膦酸强有力附着在硅酸钙水化后产物硅酸钙水凝胶表面,阻碍水化反应进一步发生,从而延长固化时间并减少骨水泥的力学强度。体外药物释放曲线表明,利塞膦酸在浸泡后2周内达到释放峰值,在其后的14天中,并无明显释放,证明硅酸钙骨水泥作为利塞膦酸载药系统具有缓释及控释的效果。吸附与脱附实验及Higuchi方程分析表明,利塞膦酸在水化时形成不溶性钙盐,因此药物释放速度受到制约。结论硅酸钙骨水泥作为利塞膦酸缓释系统具有缓释和控释的效果,有利于合并骨质疏松症患者的骨折修复与重铸。     

包裹多柔比星微球骨水泥的制备及其表征

背景:不同材料的骨水泥其性能不同,治疗的效果也会有所不同。目的:对比观察CPC、CPC/D、CPC/M/D3种材料的性能,探讨包裹多柔比星微球骨水泥的制备方法。方法:采用复乳溶剂挥发法制备多柔比星微球,将多柔比星药物微球与CPC粉末以3∶7的比例均匀混合,制备成柱状包裹药物微球骨水泥。实验分为3组:①CPC组材料中只有骨水泥,不含药物和药物微球。②CPC/D组含有多柔比星药物的骨水泥。③CPC/M/D组包裹有多柔比星药物微球的骨水泥。用扫描电镜在不同放大倍数下观察样本结构特征,测量微球的粒径。采用X射线衍射分析仪测试样品的化学成分。分别对3组骨水泥在25℃和37℃下凝结时间进行测定,并计算可注射性和孔隙率。将试件置于万能生物力学试验机上进行最大抗压强度的测定,记录标本样条的最大抗压强度和断裂强度。结果与结论:PLGA微球(100~150μm)表面光整圆滑,骨水泥与药物混合后的微结构变化不大,无法判断药物在骨水泥中的位置和特征性表现。载微球骨水泥(100~150μm)的结构疏散,均匀分布于CPC粉末之间。3种样品的XRD谱线与标准的羟基磷灰石的XRD谱线一致,其主峰位于XRD谱线32°附近。加入药物和微球并没有新的相产生。3种骨水泥刚投入生理盐水中材料均无崩解,但24h后包裹微球的骨水泥表面有明显溃散,材料不完整。CPC/M/D组凝结时间最长,CPC组凝结时间最短;37℃时,凝结时间较长;终凝时间较长,在CPC/M/D组可达45min左右。加入药物微球的CPC/M/D组可注射性能最好。CPC/M/D组的孔隙率最大,CPC组最小。CPC中加入药物微球后,其孔隙率可显著增加达61.67%。CPC组屈服应力最大,CPC/M/D组最小。当多柔比星原药和药物微球加入磷酸钙骨水泥后,其强度会有所降低,但两者之间差异并不显著。结果证实包裹多柔比星微球骨水泥的制备方法可靠,产物具有理想的结构和良好的性能。     

一种新型磷酸钙骨水泥的制备、基本性能 的研究及生物安全性评价

对研制出的钙磷比为 1.5的新型缺钙羟基磷灰石 ( CDHA)骨水泥进行了基本性能的考察 ,结果表明其凝结时间能够满足临床上的要求 ;骨水泥固化体的抗压强度随着浸泡时间的延长而增加 ,并与调和液的种类有关。生物安全性评价的结果表明 ,钙骨水泥有好的生物相容性 ,对肌肉无刺激性并具有生物降解特性     

一种可注射体内成孔的磷酸钙骨水泥

背景：磷酸钙骨水泥存在脆性大、抗水溶性(血溶性)差、力学性能不足、降解缓慢等缺点,其临床应用受到一定限制,故需要对其进行改性研究。 目的：制备一种具有一定强度、孔隙率、适合骨生长的多孔磷酸钙骨水泥生物支架材料。 方法：以磷酸钙骨水泥为基本体系,液相采用壳聚糖的弱酸溶液,以提高磷酸钙骨水泥的可塑性和黏弹性,使骨水泥具有可注射性,显著提升骨水泥的应用范围及应用舒适度。固相为双相磷酸钙(磷酸四钙+磷酸氢钙)粉体,并在固相中添加一定量的甘露醇及聚乳酸-乙醇酸共聚物作为造孔剂,制备磷酸钙支架材料。 结果与结论：此材料孔径可达到10~300 μm。添加60%致孔剂时,磷酸钙骨水泥固化体孔隙率可达到(68.3±1.5)%。磷酸钙骨水泥孔隙率的增加使材料的力学性能下降,其抗压强度从最初不含致孔剂时的(53.0±1.4) MPa下降到含60%致孔剂的(2.5±0.2) MPa。实验制备的此种多孔磷酸钙骨水泥材料,是具有一定抗压强度、较好的孔隙率,并能体内降解的可注射生物支架材料。     

医用磷酸钙骨水泥的制备及性能的实验研究

探索了磷酸四钙（Ca4（PO4）2O，TTCP）的制备，并合成了磷酸钙骨水泥（CPC），对CPC固化时间、引起浸泡液pH值的变化、抗压强度、产物物相组成及微观结构进行了研究。结果表明：在真空条件下、1500℃下煅烧6h可制得TTCP，并含有少量CaO。CPC初凝时间为4min、终凝时间为15min，浸泡1d和7d后的抗压强度分别为20MPa和35MPa，浸泡液的pH值在6．4～8．9之间变化，这些性能均符合临床用CPC的性能要求。CPC水化产物为片状或针状羟基磷灰石（Ca5（PO4）3OH，HA），相互交错呈连续分布的网状结构，这种结构有利于材料强度的提高。实验研制的CPC材料可用于骨缺损的修复治疗。     

磷酸钙骨水泥的研究进展

磷酸钙陶瓷具有良好的生物相容性和骨的传导性,在人工骨和骨材料中得到广泛的应用,而磷酸钙骨水泥(CPC)具有水化、硬化特性,具有可调和性、可塑性以及具有更大的生物降解性,因而在骨缺损的修复和重建等领域中占据着重要的地位。本文就近几年磷酸钙骨水泥的制备、水化机理、生物相容性、降解机理以及磷酸钙骨水泥在临床的应用的进展作一综述。     

抗稀散性碳酸化羟基磷灰石骨水泥的研究

目的研制一种适合出血部位植骨的碳酸化羟基磷灰石骨水泥代骨材料.方法合成碳酸化羟基磷灰石骨水泥,在固化液中按重量比添加水溶性磷酸化壳聚糖,通过固化时间、抗压强度、残余百分比、X线衍射分析、傅里叶变换红外线分析等检测方法筛选合适的配方.结果添加壳聚糖对碳酸化羟基磷灰石骨水泥的固化时间影响不大,平均固化时间为11～15min,符合临床操作要求.但是对抗压强度影响较大,由39MPa降到31MPa.壳聚糖的添加量为0.4%(质量分数)时,抗稀散达到100%.大于0.5%时,骨水泥的操作性能明显下降.添加量为1.5%时,部分标本发现少量的磷酸八钙形成,羟基磷灰石的转化受到了影响.傅里叶变换红外线分析证明,其固化产物的晶格相中含有5.6%碳酸根成分.结论磷酸化壳聚糖能明显增加碳酸化羟基磷灰石骨水泥的黏度系数,增强钙离子的熬合作用,有效抑制血液渗入材料内部,保证骨水泥的固化反应顺利进行.当壳聚糖的添加量为0.4%时,材料表现出良好的操作性能,抗稀散性达到100%,适合出血部位的骨缺损修复.     

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％。     

Effects of the granularity of raw materials on the hydration and hardening process of calcium phosphate cement

Effects of the granularity of the raw materials on the hydration and hardening process of calcium phosphate cement (CPC) composed of equimolar tetracalcium phosphate (TECP) and dicalcium phosphate anhydrous (DCPA) were investigated systematically. The variation of pH value in CPC slurry indicated that the control step of CPC hydration was the dissolution of DCPA under these experimental conditions. Reducing the particle size of DCPA could accelerate the hydration rate, and decreasing the particle size of TECP would expedite the dissolution of DCPA, which would obviously result in a faster hydration rate. The results of isothermal conduction calorimetry showed that reducing the particle size of TECP could increase the conversion ratio of starting materials to hydration products, which would lead to an increase in the compressive strength of the hardened body of CPC. The sample composed of the smallest particle size of DCPA and TECP obtained the compressive strength of 41 MPa, which would not attain the highest compressive strength, 49 MPa. The smaller the particle size of either DCPA or TECP, the shorter the setting time was. During the setting process of CPC, the microstructure progresses from a gel structure to an agglomeration-crystallization structure. The calculated values of setting time from the rheological model coincided with the experimental data very well. The parameters of AC impedance spectroscopy were closely correlated with the mean pore diameter and porosity of the CPC hardened body. The results of AC impedance spectroscopy further verified that a small particle size of raw materials could result in high hydration rate and the compressive strength of 49.1 MPa.     

Physicochemical properties of TTCP/DCPA system cement formed in physiological saline solution and its cytotoxicity

In this paper, the physicochemical properties and cytotoxicity of calcium phosphate cement (CPC), prepared by mixing cement powders of tetracalcium phosphate (TTCP) and dicalcium phosphate (DCPA) with a cement liquid of physiological saline solution, were investigated. The microstructure evolution of various hardened cement bodies and their hydration crystals as a function of immersion time in similar physiological fluids, physiological saline solution (0.9% NaCl), or simulated body fluids (SBF), were also studied. Results show that the setting time of CPC is in the range of 12-15 min, which meets the clinical application demands. We also found that the mean compressive strength of the CPC samples immersed in SBF for 3 days is 104+/-10 MPa which reaches the transverse compressive strength, 106-133 MPa, of human long bone. The results obtained from both the X-ray powder diffraction analyses (XRD) and scanning electron microscopy (SEM) observations indicated that a reinforcing effect of some remaining TTCP particles in the early stages of immersion is mainly responsible for the increase in the initial strength. Although the CPC failed to keep this high level when immersed for a longer time, the initial reinforcing effect of the remaining TTCP particles provides advantages for clinical applications. This would be effective when the material is loaded at the very beginning of the implantation, especially for the material used as a fixation, which requires a certain initial strength in the early stages of the implantation. The cytotoxicity results showed that the relative growth rate (RGR%) of L929 cells on the CPC samples using physiological saline solution as a cement liquid was slightly superior to that of the samples using the 0.5 mol/L phosphate acid solution as the cement liquid. This was most likely caused by the pH difference between the two CPC samples immersed in a DMEM-BFS medium.     

Phase evaluation of an effervescent-added apatitic calcium phosphate bone cement

Development of macroporosity during setting would allow fast bone ingrowth and good osteointegration of the implant. The interconnected macropores could be created in calcium phosphate cements (CPCs) through the addition of an effervescent porogen mixture to the component of the cements. But this addition could also affect other characteristics of CPCs, such as setting time, mechanical strength, extent of conversion of reactant to apatite phase, crystallinity, and chemical composition of apatite lattice. In this study, these properties were investigated in an effervescent-added calcium phosphate bone cement. From 0 to 20 wt % of an effervescent mixture was added to calcium phosphate cement (CPC) components and phase evaluations were performed after 24 h incubation at 37 degrees C and 28% relative humidity and 1, 3, 7, and 14 days immersion in a specific simulated body fluid. XRD and FTIR techniques were used to characterize the cement composition, crystallinity, and chemical groups in final CPCs. The results showed that addition of effervescent porogen affects the extent of conversion of reactant to apatite phase and crystallinity. In other words, using the effervescent porogen in CPCs could accelerate the rate of conversion of TTCP/DCPA reactant to apatite phase with smaller crystallites, so that it was the predominant phase (about 67%) after only 3 days soaking in SBF solution. The content of carbonate groups substituted for phosphate groups in apatite lattice increased when the effervescent additive was further added. The compressive strength of the set calcium phosphate cement decreased significantly with the addition of the effervescent agent and reached from 8 MPa for additive-free CPC to 1.3 MPa for 20% effervescent-added CPC. The compressive strength was improved after 3 days immersing of CPC in the simulated body fluid solution.     

Cephalexin-loaded injectable macroporous calcium phosphate bone cement

Different types of calcium phosphate cements (CPCs) have been studied as potential matrices for incorporating different types of antibiotics. All of these matrices were morphologically microporous whereas macroporosity is essential for rapid cement resorption and bone replacement. In this study, liberation of cephalexin monohydrate (CMH) from a macroporous CPC was investigated over 0.5-300 h in simulated body fluid and some mathematical models were fitted to the release profiles. Macroporosity was introduced into the cement matrix by using sodium dodecyl sulfate molecules as air-entraining agents and the effect of both surfactant and CMH on basic properties of the CPC was studied. Incorporation of CMH into the CPC composition increased the setting time, decreased the crystallinity of the formed apatite phase, and improved the injectability of the paste. The use of both CMH and sodium dodecyl sulfate did not affect the rate of conversion of the reactants into apatite phase while soaking the cements in simulated body fluid. Results showed that the liberation rate of the drug from porous CPC was higher than that of the nonporous CPC but same release patterns were experienced in both types of cements, that is, like to nonporous CPC, a time-dependent controlled release of the incorporated drug was obtained from macroporous CPC. The Weibull model was the best fitting-equation for release profiles of all cements. The liberated CMH was as active as fresh cephalexin. It is concluded that this macroporous CPC can be successfully used as drug carrier with controlled release profile for the treatment of bone infections.     

Self-setting bioactive calcium-magnesium phosphate cement with high strength and degradability for bone regeneration

Calcium phosphate cement (CPC) has been successfully used in clinics as bone repair biomaterial for many years. However, poor mechanical properties and a low biodegradation rate limit any further applications. Magnesium phosphate cement (MPC) is characterized by fast setting, high initial strength and relatively rapid degradation in vivo. In this study, MPC was combined with CPC to develop novel calcium-magnesium phosphate cement (CMPC). The setting time, compressive strength, phase composition of hardened cement, degradation in vitro, cells responses in vitro by MG-63 cell culture and tissue responses in vivo by implantation of CMPC in bone defect of rabbits were investigated. The results show that CMPC has a shorter setting time and markedly better mechanical properties than either CPC or MPC. Moreover, CMPC showed significantly improved degradability compared to CPC in simulated body fluid. Cell culture results indicate that CMPC is biocompatible and could support cell attachment and proliferation. To investigate the in vivo biocompatibility and osteogenesis, the CMPC samples were implanted into bone defects in rabbits. Histological evaluation showed that the introduction of MPC into CPC enhanced the efficiency of new bone formation. CMPC also exhibited good biocompatibility, biodegradability and osteoconductivity with host bone in vivo. The results obtained suggest that CMPC, having met the basic requirements of bone tissue engineering, might have a significant clinical advantage over CPC, and may have the potential to be applied in orthopedic, reconstructive and maxillofacial surgery.     

Rheological properties of concentrated aqueous injectable calcium phosphate cement slurry

In this paper, the steady and dynamic rheological properties of concentrated aqueous injectable calcium phosphate cement (CPC) slurry were investigated. The results indicate that the concentrated aqueous injectable CPC showed both plastic and thixotropic behavior. As the setting process progressed, the yield stress of CPC slurry was raised, the area of the thixotropic hysteresis loop was enlarged, indicating that the strength of the net structure of the slurry had increased. The results of dynamic rheological behavior indicate that the slurry presented the structure similar to viscoelastic body and the property of shear thinning at the beginning. During the setting process, the slurry was transformed from a flocculent structure to a net structure, and the strength increased. Different factors had diverse effects on the rheological properties of the CPC slurry in the setting process, a reflection of the flowing properties (or injection), and the microstructure development of this concentrated suspension. Raising the powder-to-liquid ratio decreased the distance among the particles, increased the initial strength, and shortened the setting time. In addition, raising the temperature improved the initial strength, increased the order of reaction, and shortened the setting time, which was favorable to the setting process. The particle size of the raw material had much to do with the strength of original structure and setting time. The storage module G' of CPC slurry during the setting process followed the rule of power law function G'=A exp(Bt), which could be applied to forecast the setting time, and the calculated results thereafter are in agreement with the experimental data.     

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.     

An effective approach by a chelate reaction in optimizing the setting process of strontium-incorporated calcium phosphate bone cement

Strontium (Sr) plays a special role in enhancing the biological osteo-stimulation of calcium phosphate cement (CPC), not only increasing osteoblast-related gene expression and the alkaline phosphatase (ALP) activity of mesenchymal stem cells (MSCs), but also inhibiting the differentiation of osteoclasts. However, the incorporation of Sr unfortunately delays the setting of CPC and weakens its mechanical properties. The purpose of this study was to overcome the aforementioned problems by introducing a chelate reaction between Ca/Sr cations from the original solid phases and carboxyl groups from the liquid phases. As expected, the setting process of Sr-incorporated CPC was optimized and the cement body after rapid hardening was mostly consisting of unreacted original solid phases. After soaking in simulated body fluid for 14 and 28 days, the composition of the cement body gradually converted to the most thermodynamic stable phase, hydroxyapatite, indicating an in vitro bioactivity. The compressive strength was not impaired in the Sr-incorporated groups, but rather, further increased over time. Higher cell proliferation rate and better ALP activity of MG-63 cells cultured on the cement surface were obtained with the presence of Sr content, demonstrating potential abilities to favor new bone formation.     

自固化磷酸钙人工骨的最新研究进展

自固化磷酸钙（CPC）是数年前在美国研制成功的一种非陶瓷型羟基磷灰石类（HAP）人工骨材料。它克服了陶瓷型HAP烧结成型、修整困难等缺点，具有制备容易、使用方便等优点。1991年以来，CPC开始在临床试用，修复颅骨缺损，获得满意效果。本文报告了CPC的最新研究结果，包括固化过程及固化工艺的研究，快速凝固型、抗水型CPC的研制，有机复合CPC水门汀的研究和作为载体缓释多种药物的体外试验结果等。随着研究范围的不断深入和扩大，CPC有可能成为未来非负重或低负重部位骨缺损修复的理想材料。