快速固化型磷酸钙骨水泥的研究

用模拟体液(simulated body fluid,SBF)作为固化液,对磷酸四钙(TTCP)+一水磷酸二氢钙(MCPM)+β-磷酸三钙(β -TCP)系骨水泥理化性质进行研究.结果表明,随液固比增大,抗压强度先增加后降低,当液固比为0.445时,抗压强度达到最大值15.23 MPa;骨水泥固化较快,液固比为0.594时,t_f为12 min;随着浸泡时间的增加抗压强度逐渐减小;X射线(XRD)和扫描电镜(SEM)分析结果显示,随液固比改变,固化反应结晶物均有羟基磷灰石(HA)相出现;浸泡后的骨水泥没有新物相产生.     

Soluble phosphate salts as setting aids for premixed calcium phosphate bone cement pastes

Recently, premixed calcium phosphate cement pastes have been proposed as biomaterials for bone tissue repair and regeneration. Use of premixed pastes saves the time and removes an extra step during a medical operation. α-Tricalcium phosphate (α-TCP) based cements set to form calcium deficient hydroxyapatite which has a moderate bioresorbtion speed. α-TCP cements require a setting aid, usually a sodium or potassium phosphate salt, to speed up the setting process. Within the current research we investigated which setting aid has significant advantage, if α-TCP is used in form of non-aqueous premixed paste. This approach offers the application of simple ingredients to produce a premixed calcium phosphate cement. The following properties of cement formulations were evaluated: cohesion, phase composition, microstructure, pH value of the liquid surrounding the cement, and compressive strength.Compositions using mixture of basic and acidic potassium phosphate salts (KH₂PO₄ and K₂HPO₄) in sufficient amounts give the best overall results (adequate cohesion and pH of the surrounding liquid, hydrolysis of starting materials within 48 h, and compressive strength of 12 ± 3 MPa). Cement prepared with basic sodium phosphate salt (Na₂HPO₄) as setting aid had considerably higher compressive strength 22 ± 1 MPa, but the pH of the surrounding liquid was basic (9.0).     

Improvement of a commercial calcium phosphate bone cement by means of drug delivery and increased injectability

Calcium phosphate cements (CPCs) have been increasingly used as synthetic bone substitutes for repair and regeneration of bone defects given their biocompatibility, resemblance to bone and malleability. Moreover, their use as local antibiotic delivery systems is of main interest against bone infections, avoiding the adverse effects of high dosages of conventional therapy. The main goals of this work were to improve the properties of a commercial CPC (Neocement®), turning it injectable, and to provide it with a new functionality as a drug delivery system able to ensure a sustained release of an antibiotic commonly used in orthopaedics (gentamicin sulphate, GS). For this, the influence of the liquid phase amount (%LP) and type of polymer contained in the formulation (chitosan, Chi, or hydroxypropyl methylcellulose, HPMC) on the basic properties of the material was evaluated. It was found that the formulation containing 42%LP + HPMC+1.87% wt GS was the best one. It showed suitable setting and mechanical properties, and injectability around 87% (much superior to the original Neocement®, with 31%). It ensured a sustained release of GS for at least 14 days, at antibacterial levels. The antibiotic released is highly effective against S. epidermidis, but also presents some antibacterial activity against S. aureus. The CPC revealed to be non-cytotoxic. Moreover, it demonstrated good flowability and connectivity with human cadaveric trabecular bone.     

磷酸镁水泥性能试验研究

采用过烧镁砂与磷酸镁二氢钾为主要原料,按照一定配比制备出可工业化生产的磷酸镁水泥。研究了磷酸镁水泥的凝结硬化时间、不同龄期的强度、干缩率、耐腐蚀性及粉煤灰对其性能的改性,并采用X射线衍射分析和扫描电镜等手段对其水化产物进行了分析。研究结果表明,磷酸镁水泥凝结时间受水灰比、成型温度影响较大,早期强度发展迅速,干缩率较小,耐腐蚀性好,掺加适量的粉煤灰可有效地提高其后期强度。该体系水化产物主要是六水磷酸镁钾晶体和一些无定形物质。     

Preparation and characterization of calcium phosphate bone cement with rapidly-generated tubular macroporous structure by incorporation of polysaccharide-based microstrips

Calcium phosphate cements (CPCs) have been extensively used as bone graft substitutes for the repair of bone defect due to its biocompatibility, osteoconductivity and in-situ setting capability. They poorly degrade thus limiting their use in tissue engineering application. A possible strategy to improve the speed of CPC degradation is to add porogen to CPC to create macropores that can enhance cement resorption and can consequently be replaced by new bone. The as-generated macropores are generally not connected because of spherical shape of the porogens which can limit the extent of newly formed bone. The aim of this study was to fabricate CPCs having tubular macroporous structure by incorporating fast-dissolving maltodextrin microstrips (MDMS) and explore their properties such as setting time, mechanical property, microstructure and degradability of the cements. The results showed that after immersing MDMS-embedded composites in simulated body fluid under physiological condition for 1 d MDMS rapidly disintegrated (more than 70%), generating tubular macropores in CPCs. The disintegration of MDMS completed in 1 week. CPCs containing MDMS lower than 30% by weight had the same final setting time as those without MDMS. The average values of compressive strength of the CPC composites decreased with the disintegration of MDMS. % Porosity and pore interconnectivity increased with increasing MDMS content. In addition, MDMS-embedded CPCs were cell friendly with excellent cell adhesion, indicating a possible candidate as bone graft substitutes.     

Preparation and characterization of calcium phosphate cement with enhanced tissue adhesion for bone defect repair

Anti-washout and tissue adhesion properties are essential for the clinical application of injectable bone materials. In this study, we prepared calcium phosphate cement (CPC) with anti-washout and tissue adhesion properties and attempted to build covalent bonds between CPC and the amino groups in bone tissue under a self-regulating pH system in the CPC (acidic to basic). The results of push-out tests demonstrated that a significant enhancement (from 6.42 ± 0.76 N to 61.5 ± 4.09 N) in tissue adhesion was obtained with the addition of 6% (w/w) oxidized sodium alginate (OSA) in CPC. The FTIR, XRD, anti-washout test, XPS, pH test, and SEM results suggested that the synergistic effect of OSA-citric acid (CA) led to the formation of a three-dimensional gel network structure in the CPC, and the Schiff base reaction between aldehyde and amino groups induced adhesion between CPC and the bone tissue. Further, the addition of less OSA had no significant negative effect on the hydration properties of CPC. Our work aims to promote the development of injectable bone material in clinical applications.     

Synthesis of weakly crystallized hydroxyapatite with Zn substitution and its effect on the calcium phosphate and calcium sulfate cements

Zn is an essential trace element in the normal growth and loading Zn into biomaterials for biomedical applications has always been a hot topic due to its immune regulation. The preparation and characterization of Zn-substituted weakly crystallized hydroxyapatite (WCH) are studied in this work, and Zn-substituted WCH was added to calcium phosphate and calcium sulfate cements (CPC and CSC) to address the effect of Zn²⁺ on the hydration crystallization behavior of calcium phosphate and calcium sulfate. Our results demonstrate that Zn²⁺ will inhibit the transformation of α-TCP to HA during the hydration reaction of CPC. And the adding of Zn²⁺ in CSC changed the crystallization morphology of calcium sulfate. The regulation of Zn on the crystallization behavior of calcium phosphate and calcium sulfate resulted in the different in vitro degradation behaviors of CPC and CSC. With the purpose of improving the biological effects of materials, the polarization of Zn²⁺ released from cements on macrophages was also characterized in this work, and the results showed that appropriate concentrations of Zn²⁺ can inhibit inflammation after stimulating RAW264.7 cells for an appropriate period of time. The presented results may be useful guidelines for the preparation and design of composite bone cement with specific Zn content.     

Synergistically reinforcement of a self-setting calcium phosphate cement with bioactive glass fibers

Calcium phosphate cements (CPCs) are highly promising for clinical uses due to their in situ-setting ability, excellent osteoconductivity and bone-replacement capability. However, the low strength limits their uses to non-load-bearing applications. In the present research, first, bioactive glass fibers (BGFs) in the ternary SiO₂-CaO-P₂O₅ system were prepared, and then the fiber composites with compositions based on CPC and BGFs were prepared and characterized. Then, the effect of structure and amount of BGF incorporation into the CPC system, and the effect of mechanical compaction on the fiber-modified system were investigated. The results showed that the compressive strength of the set cements without any BGFs was 0.635 MPa which was optimally increased to 3.69 MPa by applying 15% BGF and then decreased by further addition of it. In addition, both the work-of-fracture and elastic modulus of the cement were considerably increased after applying the fibers in the cement composition. Also, the setting time slightly decreased by applying the fibers. In summary, processing parameters were tailored to achieve optimum mechanical properties and strength. The prepared composite may be useful in surgical sites that are not freely accessible by open surgery or when using minimally invasive techniques.     

矿物掺合料改性磷酸镁水泥研究进展

在总结磷酸镁水泥水化产物、水化速度、孔结构、流动性和物理力学性能等的基础上,综述了粉煤灰、矿渣、硅灰、赤泥和偏高岭土等矿物掺合料对磷酸镁水泥的改性效果和作用机理。矿物掺合料改性磷酸镁水泥具有优异的物理力学性能和经济性,耐水性、严苛条件下耐久性、负温下水化硬化特征和矿物掺合料改性机制等课题尚待深入研究,以期为促进磷酸镁水泥及其修补砂浆在重点工程中的应用提供参考。     

Reduced graphene oxide/carbon nanotubes reinforced calcium phosphate cement

Improving the mechanical properties of calcium phosphate cement (CPC) will be helpful for expanding its application range in the treatment of bone defect. In this work, reduced graphene oxide (RGO), which has two-dimensional structure and excellent mechanical properties, and carbon nanotubes (CNTs) were used as toughening materials collectively, to enhance the mechanical properties of CPC. Setting time, morphology and mechanical properties of CPC were analyzed. The two dimensional structure of RGO could increase the interface area between RGO and substrate, which achieved an effective transfer of load between substrate and RGO. Moreover, by reasons of bridging cracks, preventing crack extension, pulling out from substrate and interface debonding, the flexural strength and compressive strength of CPC were increased by 67.1% ± 4.8% and 76.4% ± 10.6% respectively. Therefore, the CPC composite we studied has potential to be used as load-bearing substitution in bone defects.     

Solubility controlling of the precursor powders of magnesium phosphate cement by changing the powder composition

One of the important factors to introduce a cement as an injectable one is to control the setting time of the cement. In this paper to control the setting time of magnesium phosphate cement, the effect of addition of calcium and sodium on phase composition and the solubility of its precursor powders was evaluated. Three phosphate precursor powders that contained only Mg, Mg–Na and Mg–Na–Ca were synthesised via an emulsion precipitation method. Phase composition, particle size distribution and solubility of the powders were determined by XRD, laser particle size analyser and ionic chromatographic methods, respectively. Addition of calcium and sodium decreased the mean size of the powder significantly from 114 to 12?µm. Furthermore, solubility of the powders decreased by the addition of calcium and sodium.     

高性能化磷酸钙骨水泥的研究进展

磷酸钙骨水泥（CPC）作为一种新型的自固化型骨修复材料,因其具有良好的生物相容性、骨传导性、可降解性及可塑性等优点,受到了国内外众多学者的广泛关注,具有广阔的应用前景。本文从磷酸钙骨水泥高性能化着手,综述了CPC的复合物及其外添加剂的研究成果,并对新型CPC的研制进展做了介绍。     

Phase transformation on bone cement: Monocalcium phosphate monohydrate into calcium-deficient hydroxyapatite during setting

This study evaluated the phase transformation of calcium phosphate cement (CPC) using a mixture of monocalcium phosphate monohydrate (MCPM) and CaCO₃ as the solid phase and either water or a sodium phosphate buffer (SPB) solution (pH=7.0) as the liquid phase. The synthetic CPC was characterized by X-ray diffraction (XRD) analysis and transmission electron microscopy (TEM). The setting reaction in the SPB solution involved three phase transformations. Firstly, MCPM and CaCO₃ reacted with sodium phosphate immediately to form dicalcium phosphate dehydrate (DCPD) which continued to dissolve. Secondly, meanwhile, an intermediate amorphous calcium phosphate (ACP) was formed. Finally, ACP transformed into calcium-deficient hydroxyapatite (CDHA). In contrast, the reaction stopped at the first stage in water. Consequently, the SPB solution not only caused the dissolution of DCPD but also provided the buffering capacity to induce the conversion of the starting materials to CDHA.     

Cementing mechanism of potassium phosphate based magnesium phosphate cement

Magnesium phosphate cements (MPCs) are materials that belong to chemically bonded ceramic materials. They have a wide range of potential applications, due to their superior performance. In this paper, the reaction products and cementing mechanism of magnesium phosphate bonded cement based on the dead burned magnesia and the mono-potassium phosphate (MPP) are investigated. Fine powder and grains of dead burned magnesia were used to prepare pure cement paste and bonding cluster samples, respectively. The cement reaction products and their micro-morphology in the both different samples are examined. The microstructure of specimens is analyzed by SEM, TEM, XDR, and optical microscopy. Struvite of potassium (MgKPO₄·6H₂O) is observed in the reaction products. According to the analysis, it is found that struvite exists in both crystalline and amorphous form. There is also residual magnesia in the hardened cement paste. By means of microscopy observation, it can be seen that reaction products form around the unreacted magnesia and can develop into a continuum structure, which further produces the hardened paste. Struvite can grow up to form the more perfect crystal in a long term curing age, if large enough space is available during the hydration process.     

Composite monetite/amorphous calcium phosphate bone cement promotes bone regeneration

Monetite (MC) is a type of calcium phosphate cement (CPC). It has various morphologies, continuous degradation and absorption properties; however, its high porosity will affect its mechanical properties. There is minimal research on MC is immature. Amorphous calcium phosphate (ACP) is widely used and exhibits good biocompatibility; however, it is unstable. In this study, MC was combined with ACP at different weight ratios to form new types of bone cements. The mechanical properties, biocompatibility, and inductive ability for osteogenesis and osteoclasts of different MC/ACP composite bone cements were evaluated. The biocompatibility and effects on osteogenic and osteoclast differentiation of MC/ACP composite bone cements were investigated in vitro using mouse bone marrow mesenchymal stem cells (mBMMSCs) and mouse monocyte/macrophage cell line RAW 264.7. RAW 264.7 cells can differentiate into osteoclasts by osteoclast differentiation. The results indicated that the overall performance of the MC/ACP composite bone cement was better than that of the MC or ACP alone. Compared to the other groups, the biocompatibility of MC75 (75 wt% MC and 25 wt% ACP) was optimal; it was able to induce mBMMSCs osteogenesis to a greater extent. MC75 was the least favorable for the proliferation, migration, and differentiation of osteoclasts. The mechanical properties, setting time and injectability of MC75 meet clinical application requirements. This study demonstrated that MC75 is a promising bone cement for repairing bone defects.     

Immobilization of solidified ceramic forms with magnesium phosphate cement

Ceramic solidification offers higher waste loading and a more stable state than can be provided by the glass solidification method because of the stable crystalline structure of its forms, but the process of fabricating large bulk solidified ceramic forms is complicated and therefore limited in application. In this paper, particulate ceramic solidification forms were first prepared by using high-temperature sintering; particulate ceramic solidification forms were then added into a paste of magnesium phosphate cement (MPC), which form composite solidified forms after curing. The mechanical and durability properties of the samples were investigated, and the phases, microstructure, high-temperature stability, and leaching properties of samples were measured by X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, and inductively coupled plasma mass spectrometry. The results show that the solidified forms prepared have excellent mechanical properties, high-temperature stability, soaking resistance, and freeze–thaw resistance. The compressive strength of samples decreased with increasing ceramic content, with the strength reaching 27.8 MPa with a 50 wt% load content of ceramic. With adsorption of the simulated nuclides by the hydration products of cement and the retardation effect of MPC, the leaching rate of the simulated nucleus was found to be 1.86 × 10⁻⁷ cm/day, which is less than that of the ceramic solidified form. A protective layer on the surface of the solidified ceramic form with MPC can further improve the performance of the solidified form.     

钙镁磷肥发展前景综述

我国主要磷资源形成于距今6.5亿至5.5亿年前,1亿年内在扬子古海沉积了105亿t以中、低品位为主的胶磷矿。这类磷矿中的大多数含镁高,是制造钙镁磷肥的最佳原料。利用玻璃结构因子配料法可充分利用磷矿开采过程中废弃的低品位磷矿及顶板剥离层生产钙镁磷肥。并介绍中国的钙镁磷肥与日本、韩国熔成磷肥的生产现况及对比3国的售价,提出中国钙镁磷肥应与世界熔成磷肥的标准与价格接轨,有利于我国磷资源的合理利用。     

Tailoring the pore structure and property of porous biphasic calcium phosphate ceramics by NaCl additive

This study investigated the effects of NaCl additive on the phase composition, pore structure and mechanical property of porous biphasic calcium phosphate (BCP) ceramics, which were prepared by freeze-casting. The results indicated that the addition of NaCl promoted transformation of β-tricalcium phosphate to hydroxyapatite in the BCP ceramics; the OH group in HA phase of BCP ceramic was partially replaced by chloride ion. As the mass fraction of NaCl in the slurry increased from 0 to 3%, the porosity of obtained porous BCP ceramics decreased from 77.76% to 60.22%; the average width of dendritic pores increased from 74.37 µm to 111.27 µm; the compressive strength achieved threefold increase. As the amount of NaCl additive reached 4.5%, the porosity, pore width, and compressive strength of the porous BCP ceramics were comparable with those modified by 3% NaCl. NaCl is regarded as an effective additive to tailor the pore structure and property of freeze-cast porous ceramics.     

Enhancement in the osteogenesis and angiogenesis of calcium phosphate cement by incorporating magnesium-containing silicates

Based on the good osteogenic and angiogenic effects of silicon and magnesium elements, three types of micro-nano magnesium-containing silicates (MS), including akermanite (Ake, Ca₂MgSi₂O₇), diopside (Dio, CaMgSi₂O₆) and forsterite (For, Mg₂SiO₄), were incorporated into calcium phosphate cement (CPC) to improve its osteogenic and angiogenic performances for clinical application. In this present work, the physicochemical properties, osteogenesis and angiogenesis of MS/CPCs (Ake/CPCs, Dio/CPCs and For/CPCs) were investigated systematically and comparatively. The results showed that all MS/CPCs had good biomineralization and significantly stimulated the osteogenic differentiation of mBMSCs and angiogenic differentiation of HUVECs, respectively. Besides, the stimulating effects were related to not only the category of MS, but also the content of MS. The For/CPCs had a good angiogenic property but their initial setting times were beyond 60 min. The Dio/CPCs showed the lowest biological performance among the three groups of MS/CPCs due to the lower ion release (Si and Mg). The Ake was the ideal modifier that could provide CPC with appropriate physicochemical properties, better osteogenesis and angiogenesis. Simultaneously, a higher addition (10 wt%) of akermanite resulted in the best potential to bone regeneration. Taken together, this research provides an effective approach to improve the overall performance of CPC, and 10Ake/CPC is of great promising prospect in bone repair.     

Fabrication and performance of calcium phosphate cement/small intestinal submucosa composite bionic bone scaffolds with different microstructures

The microstructure of the tissue has a very important determining effect on its performance. Herein, two calcium phosphate cement (CPC)/small intestinal submucosa(SIS) composites bionic bone scaffolds with different microstructures were fabricated by rolling or/ and assembling method. The microstructure, 3D morphology, the crystal phase and mechanical properties of the scaffolds were investigated by micro CT, XRD, FIIR, SEM and electronic universal testing machines respectively. The results showed that the pore size of all scaffolds are in the range of 100–400?µm, which are beneficial to cells growth, migration, and tissue vascularization. Their porosity and the specific surface area were 14.53?±?0.76%, 8.74?±?1.38?m²/m³ and 32?±?0.58%, 26.75?±?2.69?m²/m³ separately. The high porosity and the large specific surface area can provide a larger space and contact area for cells adhesion and proliferation. Meanwhile, compressive strength of the scaffolds soaked were 10?MPa and 27?MPa, about 1.2 folds and 3.2 folds of the original scaffolds, respectively. The results are derived from different microstructures of the scaffolds and chemical bonds between SIS and new phases (hydroxyapatite), and the scaffolds performance steadily increased at near the physiological conditions. Finally, biocompatibility of the scaffolds was evaluated by CCK8, bionic microstructure scaffolds are no cytotoxicity and their biocompatibility is favorable. Based on the microstructure, compressive strength and cytotoxicity of the scaffolds, bionic Harvarsin microstructure CPC/SIS composite scaffold is expected to turn into a scaffold with the excellent properties of real bone.