Composite time-lapse computed tomography and micro finite element simulations: A new imaging approach for characterizing cement flows and mechanical benefits of vertebroplasty

Vertebroplasty has been shown to reinforce weak vertebral bodies and reduce fracture risks, yet cement leakage is a major problem that can cause severe complications. Since cement flow is nearly impossible to control during surgery, small volumes of cement are injected, but then mechanical benefits might be limited. A better understanding of cement flows within bone structure is required to further optimize vertebroplasty and bone augmentation in general. We developed a novel imaging method, composite time-lapse CT, to characterize cement flow during injection.In brief, composite-resolution time-lapse CT exploits the qualities of microCT and clinical CT. The method consists in overlaying low-resolution time-lapse CT scans acquired during injection onto pre-operative high-resolution microCT scans, generating composite-resolution time-lapse CT series of cement flow within bone.In this in vitro study, composite-resolution time-lapse CT was applied to eight intact and five artificially fractured cadaveric vertebrae during vertebroplasty. The time-lapse scans were acquired at one-milliliter cement injection steps until a total of 10 ml cement was injected. The composite-resolution series were then converted into micro finite element models to compute strains distribution under virtual axial loading. Relocation of strain energy density within bone structure was observed throughout the progression of the procedure. Interestingly, the normalized effect of cement injection on the overall stiffness of the vertebrae was similar between intact and fractured specimens, although at different orders of magnitude.In conclusion, composite time-lapse CT can picture cement flows during bone augmentation. The composite images can also be easily converted into finite element models to compute virtual strain distributions under loading at every step of an injection, providing deeper understanding on the biomechanics of vertebroplasty.     

Introduction of enzymatically degradable poly(trimethylene carbonate) microspheres into an injectable calcium phosphate cement

Poly(trimethylene carbonate) (PTMC) is an enzymatically degradable polyester with rubber-like properties. Introduction of this polymer into an injectable calcium phosphate bone cement can therefore be used to introduce macroporosity into the cement for tissue engineering purposes as well as to improve mechanical properties. Aim of this study was to investigate calcium phosphate cements with incorporated PTMC microspheres (PTMC CPCs) on their physical/mechanical properties and in vitro degradation characteristics. Therefore, composites were tested on setting time and mechanical strength as well as subjected to phosphate buffered saline (PBS) and enzyme containing medium. PTMC CPCs (12.5 and 25 wt%) with molecular weights of 52.7 kg mol(-1) and 176.2 kg mol(-1) were prepared, which showed initial setting times similar to that of original CPC. Though compression strength decreased upon incorporation of PTMC microspheres, elastic properties were improved as strain-at-yield increased with increasing content of microspheres. Sustained degradation of the microspheres inside PTMC CPC occurred when incubated in the enzymatic environment, but not in PBS, which resulted in an interconnected macroporosity for the 25 wt% composites.     

Computational modelling of the mechanical environment of osteogenesis within a polylactic acid–calcium phosphate glass scaffold

A computational model based on finite element method (FEM) and computational fluid dynamics (CFD) is developed to analyse the mechanical stimuli in a composite scaffold made of polylactic acid (PLA) matrix with calcium phosphate glass (Glass) particles. Different bioreactor loading conditions were simulated within the scaffold. In vitro perfusion conditions were reproduced in the model. Dynamic compression was also reproduced in an uncoupled fluid-structure scheme: deformation level was studied analyzing the mechanical response of scaffold alone under static compression while strain rate was studied considering the fluid flow induced by compression through fixed scaffold. Results of the model show that during perfusion test an inlet velocity of 25 μm/s generates on scaffold surface a fluid flow shear stress which may stimulate osteogenesis. Dynamic compression of 5% applied on the PLA–Glass scaffold with a strain rate of 0.005 s^?1 has the benefit to generate mechanical stimuli based on both solid shear strain and fluid flow shear stress on large scaffold surface area. Values of perfusion inlet velocity or compression strain rate one order of magnitude lower may promote cell proliferation while values one order of magnitude higher may be detrimental for cells. FEM–CFD scaffold models may help to determine loading conditions promoting bone formation and to interpret experimental results from a mechanical point of view.     

Synchrotron X-ray microtomography (on a micron scale) provides three-dimensional imaging representation of bone ingrowth in calcium phosphate biomaterials

This study used synchrotron X-ray microtomography on a micron scale to compare three-dimensional (3D) bone ingrowth after implantation of various calcium phosphate bone substitutes in a rabbit model. The advantage of using this new method for the study of biomaterials was then compared with histomorphometry for analysis of interconnection and bone ingrowth. The study focused on the newly formed bone-biomaterial interface. Macroporous Biphasic Calcium Phosphate (MBCP) ceramic blocks and two different injectable calcium phosphate biomaterials [an injectable bone substitute (IBS) consisting of a biphasic calcium phosphate granule suspension in hydrosoluble polymer and a calcium phosphate cement material (CPC)] were studied after in vivo implantation.Absorption or phase-contrast microtomography was performed with the dedicated set-up at beamline ID22. Experimental spatial resolution was between 1 and 1.4 microm, depending on experimental radiation. All calcium phosphates tested showed osteoconduction. IBS observations after 3D reconstruction showed interconnected bioactive biomaterial with total open macroporosity and complete bone ingrowth as early as 3 weeks after implantation. This experimentation was consistent with two-dimensional histomorphometric analysis, which confirmed its suitability for biomaterials. This 3D study relates the different types of bone substitution to biomaterial architecture. As porosity and interconnection increase, bone ingrowth becomes greater at the expense of the bone substitute: IBS>MBCP>CPC.     

Noninvasive bone replacement with a new injectable calcium phosphate biomaterial

The use of injectable calcium phosphate (CaP) biomaterials in noninvasive surgery should provide efficient bone colonization and implantation. Two different kinds of injectable biomaterials are presently under development: ionic hydraulic bone cements that harden in vivo after injection, and an association of biphasic calcium phosphate (BCP) ceramic granules and a water-soluble polymer vehicle (a technique particularly investigated by our group), providing an injectable CaP bone substitute (IBS). In our study, we compared these two approaches, using physicochemical characterizations and in vivo evaluations in light microscopy, scanning electron microscopy, and three-dimensional microtomography with synchrotron technology. Three weeks after implantation in rabbit bone, both biomaterials showed perfect biocompatibility and bioactivity, but new bone formation and degradation of the biomaterial were significantly greater for BCP granules than for ionic cement. Newly formed bone developed, binding the BCP granules together, whereas new bone grew only on the surface of the cement, which remained dense, with no obvious degradation 3 weeks after implantation. This study confirms that BCP granules carried by a cellulosic polymer conserve bioactivity and are conducive to earlier and more extensive bone substitution than a carbonated-hydroxyapatite bone cement. The presence of intergranular spaces in the BCP preparation, as shown on microtomography imaging, seems particularly favorable, allowing body fluids to reach each BCP granule immediately after implantation. Thus, the IBS functions as a completely interconnected ceramic with total open macroporosity. This new bone replacement approach should facilitate microinvasive bone surgery and local delivery of bone therapy agents.     

预分化脂肪干细胞与纤维蛋白胶和磷酸钙骨水泥自体异位构建血管化移植物

背景：预构骨皮瓣研究启发人们构建预构血管化骨进行游离移植来替代带血管蒂游离自体骨移植修复大段骨缺损的想法。 目的：设计一种基于预分化脂肪干细胞、纤维蛋白胶和多孔磷酸钙骨水泥支架复合体的血管化移植物。 方法：将体外分离培养的大鼠脂肪干细胞在条件培养基中进行血管内皮细胞定向分化,经鉴定活性后,复合至纤维蛋白胶和多孔磷酸钙骨水泥构建血管化组织工程支架。将血管化组织工程支架、纤维蛋白胶/多孔磷酸钙骨水泥支架及多孔磷酸钙骨水泥支架分别植入SD大鼠股四头肌肌袋内,植入后2,4周进行组织学检测、血管定量分析和Western blot检测。 结果与结论：向血管内皮细胞分化的脂肪干细胞与纤维蛋白胶和多孔磷酸钙骨水泥共培养7 d,可见细胞密度适中,与支架组织结合较好。植入实验中,各组支架孔隙中充填有纤维血管组织和脂肪组织,血管化组织工程组支架孔隙中均长入大量血管,并有小动脉长入,不同时间点的血管直径和数量及血管内皮生长因子C的表达量均优于纤维蛋白胶/多孔磷酸钙骨水泥组和多孔磷酸钙骨水泥组(P < 0.01)。表明构建的血管化组织工程支架能够实现可靠迅速血管化。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;组织工程全文链接：     

不同力学激励对骨重建数值模拟的影响

目的研究采用应变能密度、等效应力、等效应变3种不同力学激励对骨重建数值模拟结果的影响。方法建立股骨近端的二维有限元模型,基于力学稳态理论的重建控制方程并结合有限元法,分别用3种不同力学激励模拟股骨近端的内部结构及密度分布,并与CT数据计算得到的骨密度值进行定量分析比较。结果 3种力学激励模拟得到的重建结果均能反映出股骨近端的主要特征结构,但采用等效应力作为激励时得到的股骨密度曲线图的趋势和数值都与CT图像数据更为一致。结论在骨重建力学调控机制中,应力可能起主导作用。准确预测和模拟骨重建过程将对矫形外科、骨伤治疗、人工假体的优化和个体化设计等临床实践提供理论依据。     

基于Weaire-Phelan结构的Ti6Al4V多孔支架力学性能研究及数值模拟

目的 研究基于lattice Weaire-Phelan（LWP）结构支架的力学性能,并利用有限元方法精确模拟多孔支架的整个压缩过程。方法 采用选择性激光熔融（selective laser melting,SLM）技术制造具有不同孔隙率的Ti6Al4V（TC4）多孔支架。通过单轴压缩试验测试样件力学属性,并与人体骨骼及其他支架结构进行对比。验证4种材料模型对多孔支架压缩仿真结果 的影响。结果 LWP支架展现出与人体松质骨十分接近的弹性模量以及高于大多数皮质骨的屈服强度。与其他支架结构相比,LWP支架具有几乎最小的弹性模量和最大的屈服强度。利用本文提出的材料模型,即Johnson-Cook本构模型和动态几何应变失效模型（Johnson-Cook constitutive model and failure model based on dynamic geometric strain,JCDG）,模拟出的结果 与试验数据非常接近。结论 作为骨修复材料,LWP支架展现出比其他支架结构更优秀的力学性能。与其他材料模型相比,JCDG更有利于构建出合理的多孔支架压缩仿真模型。     

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。     

Introduction of gelatin microspheres into an injectable calcium phosphate cement

For tissue engineered bone constructs, calcium phosphate cement (CPC) has a high potential as scaffold material because of its biocompatibility and osteoconductivity. However, in vivo resorption and tissue ingrowth is slow. To address these issues, microspheres can be incorporated into the cement, which will create macroporosity after in situ degradation. The goal of this study was to investigate the handling properties and degradation characteristics of CPC containing gelatin microspheres. Setting time and injectability were determined and an in vitro degradation study was performed. Samples were assayed on mass, compression strength, E-modulus, and morphology. A supplementary degradation test with gelatin microspheres was performed to investigate the influence of physical conditions inside the cement on microsphere stability. The gelatin microsphere CPCs were easy to inject and showed initial setting times of less than 3 min. After 12-weeks in vitro degradation no increase in macroporosity was observed, which was supported by the small mass loss and stabilizing mechanical strength. Even a clear densification of the composite was observed. Explanations for the lack of macroporosity were recrystallization of the cement onto or inside the gelatin spheres and a delayed degradation of gelatin microspheres inside the scaffold. The supplementary degradation test showed that the pH is a factor in the delayed gelatin microsphere degradation. Also differences in degradation rate between types of gelatin were observed. Overall, the introduction of gelatin microspheres into CPC renders composites with good handling properties, though the degradation characteristics should be further investigated to generate a macroporous scaffold.     

Resorbability of bone substitute biomaterials by human osteoclasts

Third generation biomaterials are being designed with the aim that once implanted they will help the body to heal itself. One desirable characteristic of these materials in bone is their ability to be remodeled, i.e. that osteoclasts resorb the material and it is subsequently replaced by newly formed bone through osteoblastic activity. So far the only way to test this biological property of bone substitutes are animal experiments with all their limitations like ethics, costs and limited transferability to man. The present study was designed, to develop a human in vitro assay, allowing to generate human osteoclasts directly on the biomaterial. The assay was validated using calcium phosphate cement and PMMA as biomaterials. Quantification was performed by raster electron microscopy and computer assisted image analysis. Dentin was used as internal standard. Our assay shows iso-bone resorbability of calcium phosphate cement in comparison to unresorbable PMMA cement. Both current clinical orthopedic practice and future skeletal engineering may profit from the availability and use of a test system for the assessment of resorption quality. The assay presented here allows to address this question of resorbability and to select the best materials for the use as bone substitutes in specific patients.     

In vivo bone response to porous calcium phosphate cement

We conducted an in vivo experiment to evaluate the resorption rate of a calcium phosphate cement (CPC) with macropores larger than 100 microm, using the CPC called Biocement D (Merck Biomaterial, Darmstadt, Germany), which after setting only shows pores smaller than 1 microm. The gas bubble method used during the setting process created macroporosity. Preset nonporous and porous cement implants were inserted into the trabecular bone of the tibial metaphysis of goats. The size of the preset implants was 6 mm and the diameter of the drill hole was 6.3 mm, leaving a gap of 0.3 mm between implant surface and drill wall. After 2 and 10 weeks, the animals were euthanized and cement implants with surrounding bone were retrieved for histologic evaluation. Light microscopy at 2 weeks revealed that the nonporous implants were surrounded by connective tissue. On the cement surface, we observed a monolayer of multinucleated cells. Ten weeks after implantation, the nonporous implants were still surrounded by connective tissue. However, a thin layer of bone now covered the implant surface. No sign of cement resorption was observed. In contrast, the porous cement evoked a completely different bone response. At 2 weeks, bone formation had already occurred inside the implant porosity. Bone formation even appeared to occur as a result of osteoinduction. Also, at their outer surface, the porous implants were completely surrounded by bone. At 2 weeks, about 31% of the initial cement was resorbed. After 10 weeks, 81% of the initial phosphate cement was resorbed and new bone was deposited. On the basis of these observations, we conclude that the creation of macropores can significantly improve the resorption rate of CPC. This increased degradation is associated with almost complete bone replacement.     

Complexity in modeling of residual stresses and strains during polymerization of bone cement: effects of conversion, constraint, heat transfer, and viscoelastic property changes

Aseptic loosening of cemented joint prostheses remains a significant concern in orthopedic biomaterials. One possible contributor to cement loosening is the development of porosity, residual stresses, and local fracture of the cement that may arise from the in-situ polymerization of the cement. In-situ polymerization of acrylic bone cement is a complex set of interacting processes that involve polymerization reactions, heat generation and transfer, full or partial mechanical constraint, evolution of conversion- and temperature-dependent viscoelastic material properties, and thermal and conversion-driven changes in the density of the cement. Interactions between heat transfer and polymerization can lead to polymerization fronts moving through the material. Density changes during polymerization can, in the presence of mechanical constraint, lead to the development of locally high residual strain energy and residual stresses. This study models the interactions during bone cement polymerization and determines how residual stresses develop in cement and incorporates temperature and conversion-dependent viscoelastic behavior. The results show that the presence of polymerization fronts in bone cement result in locally high residual strain energies. A novel heredity integral approach is presented to track residual stresses incorporating conversion and temperature dependent material property changes. Finally, the relative contribution of thermal- and conversion-dependent strains to residual stresses is evaluated and it is found that the conversion-based strains are the major contributor to the overall behavior. This framework provides the basis for understanding the complex development of residual stresses and can be used as the basis for developing more complex models of cement behavior.     

磷酸钙生物陶瓷的孔性、内部连通性及表面形态对骨质再生的影响

磷酸钙生物陶瓷是一类具有良好生物相容性和骨传导性的生物活性材料,由于其成分与骨的无机组分基本相当,是目前公认的最具前途的硬组织修复材料,将该材料制成多孔结构,更有利于新生骨组织生长所需的物质交流,促进新生骨形成,因而成为近年来生物材料的研究热点之一。本文从多孔磷酸钙生物陶瓷与组织的响应关系角度出发,评述了近年来磷酸钙生物陶瓷的孔性、孔和孔间的内部连通性及孔的表面形态对骨质再生影响的研究进展。     

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).     

Three-dimensional,bioactive, biodegradable,polymer-bioactive glass composite scaffolds with improved mechanical properties support collagen synthesis and mineralization of human osteoblast-like cells in vitro

In the past decade, tissue engineering-based bone grafting has emerged as a viable alternative to biological and synthetic grafts. The biomaterial component is a critical determinant of the ultimate success of the tissue-engineered graft. Because no single existing material possesses all the necessary properties required in an ideal bone graft, our approach has been to develop a three dimensional (3-D), porous composite of polylactide-co-glycolide (PLAGA) and 45S5 bioactive glass (BG) that is biodegradable, bioactive, and suitable as a scaffold for bone tissue engineering (PLAGA-BG composite). The objectives of this study were to examine the mechanical properties of a PLAGA-BG matrix, to evaluate the response of human osteoblast-like cells to the PLAGA-BG composite, and to evaluate the ability of the composite to form a surface calcium phosphate layer in vitro. Structural and mechanical properties of PLAGA-BG were measured, and the formation of a surface calcium phosphate layer was evaluated by surface analysis methods. The growth and differentiation of human osteoblast-like cells on PLAGA-BG were also examined. A hypothesis was that the combination of PLAGA with BG would result in a biocompatible and bioactive composite, capable of supporting osteoblast adhesion, growth and differentiation, with mechanical properties superior to PLAGA alone. The addition of bioactive glass granules to the PLAGA matrix resulted in a structure with higher compressive modulus than PLAGA alone. Moreover, the PLAGA-BA composite was found to be a bioactive material, as it formed surface calcium phosphate deposits in a simulated body fluid (SBF), and in the presence of cells and serum proteins. The composite supported osteoblast-like morphology, stained positively for alkaline phosphatase, and supported higher levels of Type I collagen synthesis than tissue culture polystyrene controls. We have successfully developed a degradable, porous, polymer bioactive glass composite possessing improved mechanical properties and osteointegrative potential compared to degradable polymers of poly(lactic acid-glycolic acid) alone. Future work will focus on the optimization of the composite scaffold for bone tissue-engineering applications and the evaluation of the 3-D composite in an in vivo model.     

Material-dependent bone induction by calcium phosphate ceramics: a 2.5-year study in dog

Bone induction by different calcium phosphate biomaterials has been reported previously. With regard to (1) whether the induced bone would disappear with time due to the absence of mechanical stresses and (2) whether this heterotopically formed bone would give rise to uncontrolled growth, a long-time investigation of porous hydroxyapatite ceramic (HA), porous biphasic calcium phosphate ceramic (TCP/HA, BCP), porous alpha-tricalcium phosphate ceramic (alpha-TCP) and porous beta-tricalcium phosphate ceramic (beta-TCP) was performed in dorsal muscles of dog, for 2.5 years. Histological observation, backscattered scanning electron microscopy observation and histomorphometric analysis were made on thin un-decalcified sections of retrieved samples. Normal compact bone with bone marrow was found in all HA implants (n = 4) and in all BCP implants (n = 4), 48 +/- 4% pore area was filled with bone in HA implants and 41 +/- 2% in BCP implants. Bone-like tissue, which was a mineralised bone matrix with osteocytes but lacked osteoblasts and bone marrow, was found in all beta-TCP implants (n = 4) and in one of the four alpha-TCP implants. Both normal bone and bone-like tissues were confined inside the pores of the implants. The results show that calcium phosphate ceramics are osteoinductive in muscles of dogs. Although the quality and quantity varied among different ceramics, the induced bone in both HA and BCP ceramics did neither disappear nor grow uncontrollably during the period as long as 2.5 years.     

The fabrication and biochemical evaluation of alumina reinforced calcium phosphate porous implants

Alumina reinforced calcium phosphate porous implants were manufactured to improve the mechanical strength while maintaining the bioactivity of calcium phosphate ceramics. The alumina porous bodies, which provided the mechanical strength, were fabricated by a polyurethane sponge method and multiple coating techniques resulted in the porous bodies with a 90-75% porosity and a compressive strength of up to approximately 6MPa. The coating of hydroxyapatite (HAp) or tricalcium phosphate (beta-TCP) was performed by dipping the alumina porous bodies into calcium phosphate ceramic slurries and sintering the specimens. The fairly strong bonding between the HAp or TCP coating layer and the alumina substrate was obtained by repeating the coating and sintering processes. The biochemical evaluations of the porous implants were conducted by in vitro and in vivo tests. For in vitro test, the implants were immersed in Ringer's solution and the release of Ca and P ions were detected and compared with those of calcium phosphate powders. For in vivo test, the porous bodies were implanted into mixed breed dogs and bone mineral density measurements and histological studies were conducted. The alumina reinforced HAp porous implants had a higher strength than the HAp porous implants and exhibited a similar bioactivity and osteoconduction property to the HAp porous implants.     

Electrochemical microelectrodes for improved spatial and temporal characterization of aqueous environments around calcium phosphate cements

Calcium phosphate compounds can potentially influence cellular fate through ionic substitutions. However, to be able to turn such solution-mediated processes into successful directors of cellular response, a perfect understanding of the material-induced chemical reactions in situ is required. We therefore report on the application of home-made electrochemical microelectrodes, tested as pH and chloride sensors, for precise spatial and temporal characterization of different aqueous environments around calcium phosphate-based biomaterials prepared from α-tricalcium phosphate using clinically relevant liquid to powder ratios. The small size of the electrodes allowed for online measurements in traditionally inaccessible in vitro environments, such as the immediate material-liquid interface and the interior of curing bone cement. The kinetic data obtained has been compared to theoretical sorption models, confirming that the proposed setup can provide key information for improved understanding of the biochemical environment imposed by chemically reactive biomaterials.     

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.