Setting behavior,mechanical property and biocompatibility of anti-washout wollastonite/calcium phosphate composite cement

In this study, a calcium phosphate-based composite cement was fabricated by incorporating wollastonite (WS) into calcium phosphate cement (CPC). The setting behavior, microstructure, injectability, porosity, compressive strength, anti-washout property, in vitro degradation, and cell behavior of the WS/CPC composite cement were systematically investigated. The results revealed that the addition of WS promoted the hydration reaction but without affecting the hydration product of CPC. The injectability of the WS/CPC composite cement declined with the incorporation of WS to a certain extent, especially when the content of WS was higher than 20 wt%. By incorporating appropriate amount of WS into CPC, the composite cement obtained feasible setting time, enhanced compressive strength, improved anti-washout performance, and favorable biocompatibility. On the basis of its improved comprehensive application-relevant properties, the WS/CPC composite cement is prospective to be a promising biomaterial for bone defect repairing.     

Effects of zirconia additives on β-tricalcium-phosphate cement for high strength and high injectability

Injectable calcium phosphate cements (CPCs) exhibit many advantages as bone substitution materials. However, the strength of injectable CPCs after setting are often insufficient. In our previous studies, mechano-chemically modification of β-tricalcium phosphate cement powder through a planetary ball-milling process exhibited simultaneous improvement in the strength and injectability of CPC. Two plausible effects of this process are: changes in the CPC powder properties and zirconia abrasion powder contamination from the milling pot and balls. The objective of the present study is to separately evaluate these two effects on the strength and injectability of CPCs.The calculated injectability of the cement paste with and without the addition of zirconia powder were higher than 65% at 6 h after mixing. These values were much higher than that of the CPC paste without mechano-chemically modification, and similar to that of CPC with zirconia abrasion powder contamination. By contrast, the compression strength of the set CPC with zirconia powder additives were higher than that without the addition, and similar to that of CPC with zirconia abrasion powder contamination. These results suggest that the changes in the CPC powder properties due to mechano-chemically modification mainly affected the injectability of the CPC paste, and the zirconia abrasion powder contamination of the CPC powder affected the strength of the set CPC.     

The effect of tricalcium silicate incorporation on bioactivity,injectability, and mechanical properties of calcium sulfate/bioactive glass bone cement

The conventional Polymethyl methacrylate (PMMA) bone cement is not biodegradable and not bioactive to bond with the native bone and causes tissue necrosis resulting from its high exothermic polymerization. Hence, biodegradable bioactive bone cements with suitable setting time and mechanical properties should be introduced. In this study, novel bioactive bone cements containing Calcium Sulfate Hemihydrate (CSH), Bioactive Glass (BG), and Tricalcium Silicate (TSC) were developed. Firstly, CSH and BG binary system was optimized based on preliminary setting and mechanical tests. Secondly, the composite bioactive bone cements were obtained by adding different quantities of TCS to the optimized CS-BG (1.3:1 wt % ratio) system. All groups exhibited desirable handling properties, an initial setting time of lower than 15 min, injectability of greater than 85%, and controlled degradability. Moreover, they demonstrated initial compressive strength values of higher than 12 MPa, superior to trabecular bone. After 28 days of hydration, the compressive strength of the cement containing 30% TCS reached 51.04 MPa. Furthermore, the present bone cements showed favorable bioactivity and bone-bonding ability as a result of calcium carbonate and hydroxyapatite (HA) formation. Furthermore, this novel bone cement exhibited appropriate biocompatibility and mesenchymal stem cell attachment, suggesting its potential for clinical applications.     

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.     

Setting properties,mechanical strength and in vivo evaluation of calcium phosphate-based bone cements

Calcium phosphate cement (CPC) is a promising material for use in minimally invasive surgery for bone defect repair due to its similarity to the mineral phase of bone, biocompatibility, bioactivity, self-setting characteristics, low setting temperature, adequate stiffness and ease of shaping in complicated geometrics. In this study, we systematically investigate the influence of preparation variables on the final properties of CPCs. We determined the effects of CPC composition, accelerators, seed hydroxyapatite and reaction temperatures on the setting times and compressive strength of CPCs based on tetracalcium phosphate (TTCP), dicalcium phosphate dehydrate (DCPD), dicalcium phosphate anhydrous (DCPA), and α-tricalcium phosphate (α-TCP). The three types of CPCs (TTCP/DCPD, TTCP/DCPA, and TTCP/α-TCP-based bone cements) were prepared by varying the amounts of seed hydroxyapatite and citric acid used as a hardening accelerator. After 24 h of incubation, all three types of bone cements exhibited the characteristic peaks attributable to hydroxyapatite (HA) without characteristic peaks of unreacted raw materials. These results indicated that the bone cements were completely converted to HA. TTCP/DCPD-based bone cements showed faster setting times than TTCP/DCPA and TTCP/α-TCP-based bone cements. As citric acid concentrations in the liquid phase increased, the setting times of all three types of bone cements gradually decreased. However, the concentrations of seed HA in the cements were not related to significant changes in setting time. The compressive strengths of CPCs were significantly influenced by composition and reaction temperature. We also studied the effects of immersion time in physiological solution on the properties of the various CPCs. In the results of in vivo tests, subjects with bone defects implanted with CPCs exhibited more bone formation than control subjects that did not receive implantations of CPCs.     

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).     

β—TCP／MCPM体系磷酸钙骨水泥的可注射性研究

本文以β-磷酸三钙和一水合磷酸二氢钙作为磷酸钙骨水泥的固相粉料。以焦磷酸钠溶液作为液相,制备出具有良好固化性能和力学性能并可快速固化的可注射型磷酸钙骨水泥,并考察了该体系液固比、原料粒径及添加剂等制备条件对其注射性能及固化性能、力学性能的影响。实验发现适当提高液固比,增大粒径尺寸以及添加低含量硫酸钙有利于增加磷酸钙骨水泥材料的可注射性能。关键词：磷酸钙骨水泥：注射性能;β-磷酸三钙     

Evaluation of ascorbic acid-loaded calcium phosphate bone cements: Physical properties and in vitro release behavior

In this study, different concentrations of ascorbic acid (50, 100 and 200 µg/mL) were added to the liquid phase of a calcium phosphate cement (CPC). The cements were immersed in simulated body fluid (SBF) for different intervals and physical, physicochemical and mechanical properties of them were evaluated. The release of added ascorbic acid from CPCs into the SBF solution was also studied. From the results, both setting time and injectability of CPC decreased by adding ascorbic acid, however the compressive strength was sharply increased before soaking in SBF solution. But, the compressive strength values of all cements (with or without ascorbic acid) soaked in SBF solution for more than 7 d duration were comparable. The X-ray diffractometry results showed that in vitro apatite formation ability of cement reactants did not change by adding ascorbic acid. The scanning electron microscopy images indicated that morphology of the formed apatite crystals was nano-needlelike and needle diameter was less than 100 nm. The loaded ascorbic acid was slowly released from CPC into the SBF solution so that about 10% and 20% of the loaded drug was released after 504 h for the cements containing 100 and 200 µg/mL ascorbic acid, respectively. The release rate was increased when the amount of added ascorbic acid decreased by 50 µg/mL.     

Crystallization behavior mediated by silicon in the hydration reaction of polycrystalline tricalcium phosphate cements

Calcium phosphate bone cement (CPC) has the advantages of good biocompatibility, injectability and arbitrary molding, and is an ideal bone repair material. However, CPC lacks good biodegradability, which affects its application in bone repair. In our work, we improved the degradation performance of CPC through two approaches: 1. By controlling the sintering process, we synthesized tricalcium phosphate (TCP) in situ as hydration raw material and made its hydration products generate dibasic calcium phosphate (DCPD). 2. Si was introduced as an inducer of hydration crystallization behavior of CPC, and the hydration products showed a long flake-like morphology. In addition, the introduction of moderate amount of Si as a nucleating agent affected the growth and porosity of the crystals inside the CPC, and improved the mechanical properties of the CPC; The coagulation time was shortened and did not have a great impact on injectability. The strength was increased from 17 ± 1.23 MPa to 32.53 ± 8.51 Mpa, an enhancement of about 91.35%. It is proposed that Si played a role in the crystal nucleus during hydration and induced the generation of DCPD crystal phase. Then, the mass retention rate of the biphasic CPC continues to decline in the whole degradation process, which shows the sustainable degradation behavior.     

Physicochemical and biological properties of composite bone cement based on octacalcium phosphate and tricalcium silicate

Biocompatible tricalcium silicate (C₃S) bone cement is widely used as dental and bone repair material; however, its long setting time, poor injectability and low initial mechanical properties limit clinical applications. In order to improve C₃S silicate bone cement and its derivatives to play a more important role in tooth restoration, bone defect repair, implant coating and tissue engineering scaffolds, a novel C₃S and octacalcium phosphate (OCP) composite bone cement (OCP/C₃S) was prepared and evaluated for setting time, injectability, anti-flocculation, pH, microstructure, bioactivity and cytotoxicity. The setting time of the OCP/C₃S composite bone cement was controlled within the clinically operable time range (8.3–13.7 min); the cement exhibited good compressive strength, injectability (93.54%), and anti-collapse performance. The 20% OCP/C₃S composite bone cement had a compressive strength of 28.94 MPa, 93% stronger than pure C₃S (14.98 MPa). An in vitro immersion test showed that the composite bone cement had excellent hydroxyapatite forming ability, proper degradation rate, and a low pH value. Cellular experiments confirmed the low cytotoxicity of the composite bone cement and its great capacity for cell proliferation. These results indicate that 20% OCP/C₃S composite bone cement is a promising biomaterial.     

Implications of unconventional setting conditions on the mechanical strength of synthetic bone grafts produced with self-hardening calcium phosphate pastes

This work presents the effects of several factors on the mechanical strength of a calcium phosphate cement (CPC) based on alpha tricalcium phosphate and correlates the results with the microstructure and percentage of conversion to hydroxyapatite. Conversion rate increased by raising the setting temperature in the studied range (4–90 °C), but the strength exhibited an increasing-decreasing trend due to changes in the morphology of hydrated crystals. Plate-like crystals were formed in the range of 22–60 °C, mechanically reinforcing the material, whereas the formation and refinement of needle-like crystals at higher setting temperature decreased the strength. Moreover, cements with dissimilar particle sizes had different optimal hydrolysis temperatures that resulted in the maximum strength. The finest powder led to higher strength at lower setting temperature due to the formation of a more compact crystal network and higher conversion. Therefore, optimization of powder particle size may allow to achieve the highest possible strength at room temperature, being beneficial for the production of the strongest pre-set CPC-based implants without the use of energy. Furthermore, the particle size can be also engineered to produce formulations that develop the highest strength at physiological temperature, with application as injectable bone grafts. The incorporation and crosslinking of gelatine further increased the mechanical strength of pre-set cements by bridging the hydroxyapatite crystals, the setting temperature showing a similar effect to that of gelatine-free cements. In contrast, moisture decreased the strength and reduced the brittleness by solvating intramolecular association between hydroxyapatite crystals and between gelatine molecules. Moreover, large cement bodies were slightly weaker than small ones, but the size effect was not statistically significant.     

纳米二氧化硅/磷酸钙复合骨水泥的力学强度和水化过程

在磷酸钙骨水泥（CPC）中添加纳米二氧化硅（nSiO2）获得了nSiO2/CPC复合骨水泥。利用维卡仪、万能压力试验机和热导式等温量热仪研究了nSiO2的添加量对nSiO2/CPC复合骨水泥的凝结时间、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添加的nSiO2对nSiO2/CPC复合骨水泥固化产物的相组成和断面形貌的影响。研究结果表明：nSiO2添加量为5%的nSiO2/CPC复合骨水泥凝结时间由16 min缩短到10 min,抗压强度由原来的（24 2）MPa增加到（33 4）MPa,提高了38%,但添加超过5%的nSiO2会影响水化产物磷灰石的生成从而使复合骨水泥的力学强度下降。在水化反应过程中,一方面nSiO2作为填料,吸附了固化液中的水导致CPC的实际固液比增大,减弱了CPC的水化进程,由于实际固化液下降也减少了水化产物的孔隙大小和数目;另一方面,nSiO2与水化产生的Ca（OH）2发生化学反应形成CSH凝胶,改善了nSiO2和CPC基体之间的界面结合。这两方面的作用结果使得添加适量的nSiO2可以提高nSiO2/CPC复合骨水泥的抗压强度,缩短其凝结时间。     

Study on the improvement of compressive strength and fracture toughness of calcium phosphate cement

Calcium phosphate cement (CPC) has superior properties, such as excellent bioactivity, biocompatibility, osteoconductivity and degradability, since its hydration product is hydroxyapatite (HA). As a novel cement material, CPC also shows injectable and self-setting properties. However, the compressive strength (CS) and fracture toughness of most CPCs are far lower than that of human weight-bearing bones, which largely limit their applications in the repairment of weight-bearing bones. To improve the CS and fracture toughness of CPC, several methods, including in-situ reinforcement by Ca4(PO4)2O (TTCP) ceramic particles, suitable nanofibers are introduced in this study. The maximal CS of CPC prepared with TTCP (average particle size of 22.3 ± 0.4 μm) reached to 98.4 MPa, which is close to the strength of human long bones. The enhanced CS of CPC was attributed to the in-situ reinforcing effect of residual TTCP particles. Tendon collagen slices and HA nanofibers were used to improve the fracture toughness of CPC. The flexural strength (FS) and the work of facture (WOF) of CPC were slightly increased by adding HA nanofibers but was significantly increased by the addition of tendon collagen slices. With 1.000 wt% tendon collagen slices, the FS and WOF of CPC were increased by 61.3% and 22.6 times, respectively.     

Role of iron on physical and mechanical properties of brushite cements,and interaction with human dental pulp stem cells

Improving the physical, mechanical and biological properties of brushite cements (BrC) is of a great interest for using them in bone and dental tissue engineering applications. The objective of this study was to incorporate iron (Fe) at different concentrations (0.25, 0.50, and 1.00 wt%) to BrC and study the role of Fe on phase composition, setting time, compressive strength, and interaction with human dental pulp stem cells (hDPSCs). Results showed that increase in Fe concentration increases the β-tricalcium phosphate (β-TCP)/dicalcium phosphate dihydrate (DCPD) ratio and prolongs the initial and final setting time due to effective role of Fe on stabilizing the β-TCP crystal structure and retarding its dissolution kinetic, in a dose dependent manner where the highest setting time was recorded for 1.00 wt% Fe–BrC sample. Addition of low concentrations of Fe (0.25 and 0.50 wt%) did not have adverse effect on compressive strength and strength was in the range of 5.7–7.05 (±~1.4) MPa; however, presence of 1.00 wt% Fe decreases the strength of BrC from 7.05 ± 1.57 MPa to 3.12 ± 1.06 MPa. Interaction between the BrCs and hDPSCs was evaluated by cell proliferation assay, scanning electron microscopy, and live/dead staining. Low concentrations of 0.25, and 0.50 wt% of Fe did not have any adverse effect on cell attachment and proliferation; while significant decrease in cellular activity was evident in BrC samples doped with 1.00 wt %. Together, these data show that low concentrations of Fe (equal or less than 0.50 wt %) can be safely added to BrC without any adverse effect on physical, mechanical and biological properties in presence of hDPSCs.     

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.     

Physical and physicochemical evaluation of calcium phosphate cement made using human derived blood plasma

Abstract

In the present work, calcium phosphate cement was made by mixing a solid phase and blood plasma as liquid phase. The basic properties of the cement (called BPC) were compared with those of conventional calcium phosphate cement (c-CPC) where distilled water was used as liquid. BPC had better consistency and injectability than c-CPC but longer setting time. In both cements, the reactants were converted into apatite phase after immersing in simulated body fluid but the phase formed in BPC had lower crystallinity than the phase formed in c-CPC. The set BPC was stronger than c-CPC, having a compressive strength (CS) of about 2–6 MPa after 24 h incubation at 37°C. The CS reduced during soaking at early stage but was relatively improved at the end of soaking period (day 7). In contrast, an increase in CS was observed in c-CPC during soaking period.     

Improvement of in vitro osteogenesis and antimicrobial activity of injectable brushite for bone repair by incorporating with Se-loaded calcium phosphate

The main objective of this research is to study the effect of selenium (Se) on injectable brushite cement (Bru) derived from Se-loaded cement starting calcium phosphate powder (SP) to reveal whether injectable Se-loaded Bru has potential for bone repair. Se was incorporated into Bru by cement SP with a Se/P molar ratio of 0.05, 0.10, and 0.15, respectively. The results show that although the cement SP changes from β-calcium phosphate to hydroxyapatite as the Se content increases, brushite is still the dominant crystalline phase of the cements. The increase of Se concentration prolongs the cement setting time and promote the cement injectability, however, excellent anti-washout ability and degradability is observed for all the cements. Moreover, the cements with higher content of Se release out Se faster when soaking in phosphate buffer saline. The cell experimental results show that cements with a Se/P of 0.05 and 0.10 can not only be beneficial for osteoblastic MG63 cells adhesion and proliferation but also enhance cell mineralization property, while the cement with a Se/P ratio of 0.15 shows cytotoxicity. Furthermore, both the agar plate tests and the broth antimicrobial tests reveal that Se-loaded Bru can significantly inhibit the growth of E. coil, S. aureus, and P. aeruginosa. The antibacterial activity increases with the increase of Se concentration in the cement. Therefore, the biological performance of injectable Se-loaded brushite cement is dose-dependent and brushite cement with an appropriate dose of Se has potential for bone repair application.     

Fast setting tricalcium silicate/magnesium phosphate premixed cement for root canal filling

MTA-based root-end filling is a promising therapeutic approach for root repair, however, difficult handling characteristics, presence of toxic elements in the material composition and long setting time are main drawbacks for clinical applications. The purpose of this study was to develop a novel fast setting silicate based premixed cement for endodontic use. The premixed cement contained tricalcium silicate (C3S) as the main constituent for hydration, magnesium phosphate cement (MPC) as setting accelerators and glycerol as water-miscible liquid. The physicochemical properties and antibacterial property of the novel cements were evaluated. Moreover, biocompatible zirconium oxide (ZrO₂) was chosen as radiopacifying agent added into the premixed cement. The radiopacity, physicochemical properties, antibacterial property and cytotoxicity of the radiopaque premixed calcium silicate based cements were evaluated. The setting time of the premixed MPC/C3S cements could be modulated within the range from 70 min to 205 min by adjusting the content of MPC. Meanwhile, the premixed MPC/C3S cement displayed good flowability and injectability when the amount of MPC less than 20%. The addition of ZrO₂ provided the premixed MPC/C3S cement with excellent radiopacity while had no significant effects on the setting time, flowability, film thickness, injectability and washout resistance. Moreover, the premixed cement with or without ZrO₂ had good antibacterial property and cytotoxicity. Our results indicated that the premixed MPC/C3S/ZrO₂ cement could be considered as a promising candidate for application in endodontics owing to its desirable physicochemical properties, antibacterial activity and cytocompatibility, especially relatively short setting time and good sealing ability.     

Anti-washout tricalcium silicate cements modified by konjac glucomannan/calcium formate complex for endodontic applications

Although tricalcium silicate (TCS)-based cement showed a great clinical success as the dental filling material, a big challenge encountered by TCS is its poor anti-washout property. Thus, the purpose of this study is to develop a novel TCS-based cement with excellent anti-washout ability by incorporation of konjac glucomannan (KGM)/calcium formate (CF) complex. The self-setting characteristics, anti-washout ability, setting time, compressive strength, porosity, injectability and flowability of the cements were investigated. Furthermore, antibacterial property and cell cytocompatibility of TCS/CF were also assessed. The results showed that KGM could enhance the washout resistance of TCS pastes while it hindered hydration reaction. CF can further increase the anti-washout ability of TCS cement and shorten its setting time from 420 to 174 min because of the accelerating effect of CF on hydration kinetics of TCS. Compared with TCS pastes, TCS cement containing CF showed an increased compressive strength while the addition of CF decreased the injectability of pastes without an obvious effect on flowability. The antibacterial activity of TCS/CF against S. aureus increased with the amount of CF. Moreover, TCS/CF had good cell cytocompatibility. Our results suggested that incorporation of KGM/CF is a superior strategy to enhance the anti-washout ability of TCS-based dental cements, which have the potential use for endodontic applications.     

The effect of carboxylic acids and phosphate salts additives on the properties of chondroitin sulfate calcium phosphate cements

The use of liquid phase additives is a strategy to improve the physicochemical, mechanical, and biological properties of calcium phosphate cements. In this study, TTCP and α-TCP particles were synthesized using the solid-state reaction method. Apatite cements were prepared by mixing TTCP/DCPD/α-TCP powders and liquid phases containing chondroitin sulfate with various additives of carboxylic acids and phosphate salts. The formation of hydroxyapatite and consumption of raw materials as well as the acceleration and deceleration periods through cementation process were investigated by XRD and DSC experiments, respectively. In addition, the morphology, setting time, porosity, compressive strength, degradation, in-vitro bioactivity and cytotoxicity were studied. The results showed that the approximate amount of hydroxyapatite resulting from the cementation process was divergent in the presence of liquid phase additives. The use of phosphate salt additives presented better results compared to carboxylic acid ones regarding hydroxyapatite cement product formation, compressive strength, hardening, setting, and cytotoxicity. All cements showed, generally a similar tendency to form dense hydroxyapatite on their outer surfaces through immersion in the simulated body fluid. The cement containing Na₂HPO₄ salt exhibited the lowest cytotoxicity and highest strength. The ALP assay and the morphological behavior of MG63 cells indicated the good activity and proper cell adhesion of this cement.