Properties Of Calcium Phosphate Cement Research Articles

The Osteogenic Properties of Calcium Phosphate Cement Doped with Synthetic Materials: A Structured Narrative Review of Preclinical Evidence.

Bone grafting is commonly used as a treatment to repair bone defects. However, its use is challenged by the presence of medical conditions that weaken the bone, like osteoporosis. Calcium phosphate cement (CPC) is used to restore bone defects, and it is commonly available as a bioabsorbable cement paste. However, its use in clinical settings is limited by inadequate mechanical strength, inferior anti-washout characteristics, and poor osteogenic activity. There have been attempts to overcome these shortcomings by adding various natural or synthetic materials as enhancers to CPC. This review summarises the current evidence on the physical, mechanical, and biological properties of CPC after doping with synthetic materials. The incorporation of CPC with polymers, biomimetic materials, chemical elements/compounds, and combination with two or more synthetic materials showed improvement in biocompatibility, bioactivity, anti-washout properties, and mechanical strength. However, the mechanical property of CPC doped with trimethyl chitosan or strontium was decreased. In conclusion, doping of synthetic materials enhances the osteogenic features of pure CPC. The positive findings from in vitro and in vivo studies await further validation on the efficacy of these reinforced CPC composites in clinical settings.

A novel anti-washout curing solution of calcium phosphate cement prepared via irradiation polymerization.

The anti-washout ability of calcium phosphate cement (CPC) determines its effectiveness in clinical application. In the current research, the common method for improving the anti-washout ability of CPC is to add anti-washout polymer agents. Sodium polyacrylate powder is an excellent anti-washout agent but when bonded with CPC it basically degrades the anti-washout performance of CPC after γ-ray irradiation, and is widely used in the sterilization process of CPC products. Therefore, we propose a method for the preparation of a sodium polyacrylate solution through irradiation polymerization as curing solution for CPC. This method first uses γ-ray irradiation sterilization to improve the anti-washout ability of CPC directly. It not only avoids the adverse effects of γ-rays on anti-washout agents, but also the CPC blended using this sodium polyacrylate solution had good biological properties and injectability. It provides a new method for promoting the anti-washout properties of calcium phosphate cement, which is of great significance for expanding the clinical application of CPC.

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.

364 A Novel Preparation of Bone Cement for Vertebroplasty: Can Strontium Folate Improve the Mechanical and Biological Properties of Calcium Phosphate Cement?

Abstract Aim Bone cements currently used for vertebral body augmentation procedures lack biological properties that allow them to osseointegrate. Strontium folate (SrFo) has been shown to increase the viability of human osteoblast (HOb) cells. The potential of a novel preparation of calcium phosphate cement (CPC) with added SrFo is explored to investigate whether SrFo can increase its biocompatibility. Method Brushite-forming CPCs with 0% (negative control) and 5% and 10% weight-weight additions of SrR (positive control) and SrFo were formulated. Initial (Ti) and final (Tf) setting times were measured. Mechanical analyses included ultimate compressive strength and plane strain fracture toughness. Topography and distribution analyses occurred during materials characterisation and in vitro analysis using scanning electron microscopy (SEM). Results There was no significant difference in the Ti between the CPCs, but significantly greater Tf for all SrFo-CPCs. There was no significant difference in the compressive strength between the CPCs, but a significantly decreased fracture toughness in all SrFo-CPCs. SEM revealed non-homogeneous structures in all SrFo-CPCs. Whilst the pH of the HOb cell culture medium remained the same for all CPCs, the proportion of dead cells was significantly higher than that of alive cells. Conclusions The addition of SrFo did not produce any significant differences in the material characteristics of the cements, nor the in vitro properties, except for a prolonged setting time. Future studies should seek to determine the osteogenic nature of SrFo by altering the formulation of the CPCs to a non-toxic preparation, such as apatite-forming cements which are known to have superior mechanical properties.

Effect of the liquid-to-powder ratio on physicochemical properties of calcium phosphate cements and of these properties over Biofilm thickness of adhered Staphylococcus Aureus

Tricalcium phosphate (TCP) synthetized by high temperature solid state reaction at 1400°C and three derived calcium phosphate cements (CPCs) prepared at liquid to powder (L/P) ratios of 0.33, 0.44 and 0.55 ml/g, respectively, were physicochemically characterized. Calcium deficient hydroxyapatite crystals were identified by scanning electron microscopy on CPC, and differences in crystal sizes were observed at different L/P ratios. Also, the biofilm thickness of two Staphylococcus Aureus (S.aureus) strains grown for 24 hours on the three CPC are reported. A dependence of the biofilm thickness with the specific surface area (SSA) of CPC was identified. They are directly proportional for non-extracellular polysaccharide substances (EPS) producing S.aureus and inversely proportional for EPS producing S.aureus. Non-proportional behavior between the SSA and mechanical strength of the CPC was observed as L/P ratio increases.

Self-healing capacity of fiber-reinforced calcium phosphate cements

A major problem concerning the mechanical properties of calcium phosphate cements (CPC) is related to their inherent brittleness, which limits their applicability to non-load bearing bone defects. In this work the preparation of a damage tolerant CPC is presented, where the incorporation of functionalized carbon fibers facilitates steady state flat crack propagation with crack openings below 10 µm. A subsequent self-healing process in simulated body fluid, that mimics the in vivo mineralization of bioactive surfaces, closes the cracks and completely restores the mechanical properties. Hereby, two pathways of self-healing are presented: i) intrinsic healing that bases on the inherent bioactive properties of the cement matrix and chemically treated fibers, and ii) capsule based extrinsic healing, where H2PO4- is released as an initiator for the apatite formation. Such damage tolerant CPCs with self-healing capacity are of particular interest to increase the lifetime of implants as well as in the field of load-bearing bioceramics.

Experimental and numerical analysis on bending and tensile failure behavior of calcium phosphate cements

Since their discovery in the 1980s, injectable self-setting calcium phosphate cements (CPCs) are frequently used in orthopedic, oral and maxillofacial surgery due to their chemical resemblance to the mineral phase of native bone. However, these cements are very brittle, which complicates their application in load-bearing anatomical sites. Polymeric fibers can be used to transform brittle calcium phosphate cements into ductile and load-bearing biomaterials. To understand and optimize this process of fiber reinforcement, it is essential to characterize the mechanical properties of fiber-free calcium phosphate matrices in full detail. However, the mechanical performance of calcium phosphate cements is usually tested under compression only, whereas bending and tensile tests are hardly performed due to technical limitations. In addition, computational models describing failure behavior of calcium phosphate cements under these clinically more relevant loading scenarios have not yet been developed. Here, we investigate the failure behavior of calcium phosphate cements under bending and tensile loading by combining, for the first time, experimental tests and numerical modeling. To this end, a 3-D gradient-enhanced damage model is developed in a finite element framework, and numerical results are correlated to experimental three-point bending and tensile tests to characterize the mechanical properties of calcium phosphate cements in full detail. The presented computational model is successfully validated against experimental results and is able to predict the mechanical response of calcium phosphate cement under different types of loading with a unique set of parameters. This model offers a solid basis for further experimental and computational studies on the development of load-bearing bone cements.

Sterilization effects on the handling and degradation properties of calcium phosphate cements containing poly (D,L -lactic-co-glycolic acid) porogens and carboxymethyl cellulose.

Injectable, self-setting calcium phosphate cements (CPCs) are synthetic bone substitutes considered favorable for the repair and regeneration of bone due to their osteocompatibility and unique handling properties. However, their clinical applicability can be compromised due to insufficient cohesion upon injection into the body coupled with poor degradation rates that restricts new bone formation. Consequently, carboxymethyl cellulose (CMC) was incorporated into CPC formulations to improve their cohesion and injectability while poly (D,L -lactic-co-glycolic acid) (PLGA) porogens were added to introduce macroporosity and improve their biodegradation rate. Like most biomaterials, CPCs are gamma irradiated before clinical use to ensure sufficient sterilization. However, it is well known that gamma irradiation also reduces the molecular weight of CMC and PLGA via chain scission, which affects their material properties. Therefore, the aim of this study is to measure the effect that gamma irradiation has on the molecular weight of CMC at varying doses of 15, 40, or 80 kGy and investigate how this affects the handling (i.e., injectability, cohesion, washout, and setting times) and in vitro degradation behavior of CPC formulations. Results reveal that the molecular weight of CMC decreases with increasing gamma irradiation dose, thereby reducing the viscosifying capabilities of CMC, which causes CPCs to deteriorate more readily. Further, the addition of CMC seems to inhibit the degree of phase transformation during cement setting while the subsequent reduction in molecular weight of PLGA after gamma irradiation improves the in vitro degradation rate of CPCs due to the faster degradation rate of low molecular weight PLGA. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2216-2228, 2019.

Improvement of anti-washout property of calcium phosphate cement by addition of konjac glucomannan and guar gum.

The inferior anti-washout property of injectable calcium phosphate cement (CPC) limits its wider application in clinic. In this study, the improvement of anti-washout performance of CPC by addition of konjac glucomannan or guar gum, which was dissolved in the CPC liquid, was first studied. The influence of KGM/GG blend with different mass ratios on the anti-washout property, compressive strength and in vitro cytocompatibility of CPC was estimated. The results revealed that small amount of KGM or GG could obviously enhance the anti-washout property of CPC. Moreover, the washout resistance efficiency of KGM/GG blend was better than KGM or GG alone. The addition of KGM/GG blend slightly shortened the final setting time of CPC. Although the introduction of KGM/GG blend reduced the compressive strength of CPC, the compressive strength still reached or surpassed that of human cancellous bone. The best KGM/GG mass ratio was 5:5, which was most efficient at not only reducing CPC disintegration, but also increasing compressive strength. The addition of KGM/GG blend obviously promoted the cells proliferation on the CPC. In short, the CPC modified by KGM/GG blend exhibited excellent anti-washout property, appropriate setting time, adequate compressive strength, and good cytocompatibility, and has the potential to be used in bone defect repair. The addition of KGM/GG blend significantly improved the anti-washout property of CPC. The best KGM/GG mass ratio was 5:5, which was most efficient in reducing the CPC disintegration.

Setting time evaluation of injectable carbonate apatite cement using various sodium carboxymethylcellulose (Na CMC) concentration

Introduction: The injectable calcium phosphate cement has the advantage to be used in the bone defect with the limited access which supports a minimally invasive surgical technique. These Injectability properties of calcium phosphate cement can be modified by adding a sodium carboxymethylcellulose (Na CMC). The aim of this present study is to investigate the setting time of injectable bone cement based on CO3Ap using various Na CMC concentration. Methods: Vaterite (a polymorph of CaCO3) and Dicalcium Phosphate Anhydrous (DCPA) as powder phase mixed with 0.2 mol/L Na2HPO4 solution containing 1% polyethylene glycol (PEG) and various concentration of Na CMC as followed 0.5%, 1%, 1.5%, and 2%, respectively. Each concentration groups was consisting of 5 samples from total 20 samples. Powder and liquid phase was mixed with a spatula at a liquid to powder (L/P) ratio of 0.4. The setting time of CO3Ap cement was evaluated according to the modification method standardized by ISO 1566 for dental zinc phosphate cement using a custom fabricated Vicat needle apparatus. The cement was maintained at 37ºC and 100% relative humidity as a standard requirement. Results: The mean value of setting time cement was as followed 0.5% Na CMC 35:06 minutes, 1% Na CMC 38:48 minutes, 1.5% Na CMC 40:06 minutes, and 2% Na CMC 41:30 minutes. The result is statistically significant (p<0.05) with the group of 0.5% Na CMC compared to others group. Conclusion: Increasing the concentration of Na CMC could prolong the setting time of CO3Ap cement.

Improvement of physical properties of calcium phosphate cement by elastin-like polypeptide supplementation

Calcium phosphate cements (CPCs) are synthetic bioactive cements widely used as hard tissue substitutes. Critical limitations of use include their poor mechanical properties and poor anti-washout behaviour. To address those limitations, we combined CPC with genetically engineered elastin-like polypeptides (ELPs). We investigated the effect of the ELPs on the physical properties and biocompatibility of CPC by testing ELP/CPC composites with various liquid/powder ratios. Our results show that the addition of ELPs improved the mechanical properties of the CPC, including the microhardness, compressive strength, and washout resistance. The biocompatibility of ELP/CPC composites was also comparable to that of the CPC alone. However, supplementing CPC with ELPs functionalized with octaglutamate as a hydroxyapatite binding peptide increased the setting time of the cement. With further design and modification of our biomolecules and composites, our research will lead to products with diverse applications in biology and medicine.

Improved Biological Properties of Calcium Phosphate Cement by Nacre Incorporation: An In Vitro Study

Improved Biological Properties of Calcium Phosphate Cement by Nacre Incorporation: An <i>In Vitro</i> Study

Reduced graphene oxide/carbon nanotubes reinforced calcium phosphate cement

Abstract 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.

Novel Injectable Calcium Phosphate Bone Cement from Wet Chemical Precipitation Method

Calcium phosphate cement has been prepared via chemical precipitation method for injectable bone filling materials. Calcium hydroxide, Ca(OH)2, and diammonium hydrogen phosphate, (NH4)2HPO4, were used as calcium and phosphorus precursors respectively. The synthesized powder was mixed with water at different powder-to-liquid (P/L) ratios, which was adjusted at 0.8, 0.9, 1.0, 1.1 and 1.2. The influence of P/L ratio on the injectability, setting time and mechanical strength of calcium phosphate cement paste has been evaluated. The synthesized powder appeared as purely hydroxyapatite with nanosized and agglomerated spherical particles. All cement pastes show excellent injectability except for the paste with P/L ratio 1.2. Calcium phosphate cement with P/L ratio 1.1 shows the ideal cement for bone filler application with good injectability, the initial and final setting times of 30 min and 160 min, and the compression strength of 2.47 MPa. The result indicated that the newly developed calcium phosphate cement is physically suitable for bone filler application. This paper presents our investigation on the effect of P/L ratio on the handling and mechanical properties of calcium phosphate cement prepared via wet chemical precipitation method.

Biomechanical and biocompatible enhancement of reinforced calcium phosphate cement via RGD peptide grafted chitosan nanofibers

<b>Objective:</b> To analysis the biomechanical and biocompatible properties of calcium phosphate cement (CPC) enhanced by chitosan short nanofibers(CSNF) and Arg-Gly-Asp (RGD). <b>Methods:</b> Chitosan nanofibers were prepared by electrospinning, and cut into short fibers by high speed dispersion. CPC with calcium phosphorus ratio of 1.5:1 was prepared by Biocement D method. The composition and structure of CPC, CSNF, RGD modified CSNF (CSNF-RGD), CSNF enhanced CPC (CPC-CSNF), RGD modified CPC-CSNF (CPC-CSNF-RGD) were observed by infrared spectrum, X-ray diffraction (XRD) and scan electron microscopy (SEM). The mechanical properties were measured by universal mechanical testing instrument. The adhesion and proliferation of MC3T3 cells were assessed using immunofluorescence staining and MTT method. <b>Results:</b> The distribution of CSNF in the scaffold was homogeneous, and the porous structure between the nanofibers was observed by SEM. The infrared spectrum showed the characteristic peaks at 1633 nm and 1585 nm, indicating that RGD was successfully grafted on chitosan nanofibers. The XRD pattern showed that the bone cement had a certain curability. The stain-stress test showed that break strengths were (17.74±0.54) MPa for CPC-CSNF and (16.67±0.56) MPa for CPCP-CSNF-RGD, both were higher than that of CPC(all <i>P</i><0.05). The immunofluorescence staining and MTT results indicated that MC3T3 cells grew better on CPC-CSNF-RGD after 240 min of culture(all <i>P</i><0.05). <b>Conclusion:</b> CSNF-RGD can improve the biomechanical property and biocompatibility of CPC, indicating its potential application in bone tissue repair.

Modification of calcium phosphate cement with poly (γ-glutamic acid) and its strontium salt for kyphoplasty application

To meet the requirements of minimally invasive surgical treatments for osteoporotic vertebral compression fracture, various strategies have been proposed to enhance the properties of calcium phosphate cement (CPC). Here, a new strategy was developed by incorporating poly (γ-glutamic acid) (γ-PGA) and its strontium salt into the formulation of alpha tricalcium phosphate (α-TCP)-based CPC. Effects of γ-PGA on the injectability, cohesion, setting times, mechanical compressive strengths and cytocompatibility were systematically studied. Results showed that the injectability, cohesion and setting times were considerably improved by introducing γ-PGA into the CPC. Moreover, after setting for 7days, the compressive strengths increased from 14.6±1.4MPa for pure CPC to 35.3±1.7MPa for CPC with 8.9wt% γ-PGA and further to 61.2±5.4MPa for CPC with 8.9wt% γ-PGA combined with its strontium salt. In vitro osteoblast proliferation tests showed that the group of CPC modified by γ-PGA and its strontium salt had better cytocompatibility than the pure CPC group. All results suggest that optimal properties were obtained for the cement with 8.9wt% γ-PGA added to its solid phases and using strontium salt as the reactive liquid phase, making it as a promising candidate for application in kyphoplasty.

Compressive fatigue properties of an acidic calcium phosphate cement\u2014effect of phase composition

Calcium phosphate cements (CPCs) are synthetic bone grafting materials that can be used in fracture stabilization and to fill bone voids after, e.g., bone tumour excision. Currently there are several calcium phosphate-based formulations available, but their use is partly limited by a lack of knowledge of their mechanical properties, in particular their resistance to mechanical loading over longer periods of time. Furthermore, depending on, e.g., setting conditions, the end product of acidic CPCs may be mainly brushite or monetite, which have been found to behave differently under quasi-static loading. The objectives of this study were to evaluate the compressive fatigue properties of acidic CPCs, as well as the effect of phase composition on these properties. Hence, brushite cements stored for different lengths of time and with different amounts of monetite were investigated under quasi-static and dynamic compression. Both storage and brushite-to-monetite phase transformation was found to have a pronounced effect both on quasi-static compressive strength and fatigue performance of the cements, whereby a substantial phase transformation gave rise to a lower mechanical resistance. The brushite cements investigated in this study had the potential to survive 5 million cycles at a maximum compressive stress of 13 MPa. Given the limited amount of published data on fatigue properties of CPCs, this study provides an important insight into the compressive fatigue behaviour of such materials.

Моделювання впливу наномагнетиту на властивості біогенного гідроксиапатиту

The aim of this article is to investigate with the help of modeling non-stationary process of influence of ferromagnetic additives on the physicochemical properties of the material produced on the basis of biogenic hydroxyapatite doped nanomagnetite. The simulation conditions specified amount of dopant, based on the medical devices produced by biological material, and in the test samples did not exceed 2% by weight. The model takes into account the limitations that the investigated material have the form of a powder or pressed tablets were obtained with the heat treatment temperature to below the Curie point of iron oxide in various gas atmospheres. The simulation changes the microstructure of the sample for the study of material properties, as well as simulated physiological peculiarities of the environment.The comparative objective evaluation of the dynamics of the solubility of modern hydroxyapatite composite biomaterials in artificial blood plasma SBF has been presented. The studies were conducted on the 2­nd, 5­th and 7­th days. As the main criterion for the dissolution of plastic materials the loss of their mass has been adopted. It is proved signicantly higher solubility properties of calcium phosphate cement, mass loss rates are much higher than values of ceramic biological and synthetic hydroxyapatite materials.

Effects of Pore Size on the Osteoconductivity and Mechanical Properties of Calcium Phosphate Cement in a Rabbit Model.

Calcium phosphate cement (CPC) porous scaffold is widely used as a suitable bone substitute to repair bone defect, but the optimal pore size is unclear yet. The current study aimed to evaluate the effect of different pore sizes on the processing of bone formation in repairing segmental bone defect of rabbits using CPC porous scaffolds. Three kinds of CPC porous scaffolds with 5 mm diameters and 12 mm length were prepared with the same porosity but different pore sizes (Group A: 200-300 µm, Group B: 300-450 µm, Group C: 450-600 µm, respectively). Twelve millimeter segmental bone defects were created in the middle of the radius bone and filled with different kinds of CPC cylindrical scaffolds. After 4, 12, and 24 weeks, alkaline phosphatase (ALP), histological assessment, and mechanical properties evaluation were performed in all three groups. After 4 weeks, ALP activity increased in all groups but was highest in Group A with smallest pore size. The new bone formation within the scaffolds was not obvious in all groups. After 12 weeks, the new bone formation within the scaffolds was obvious in each group and highest in Group A. At 24 weeks, no significant difference in new bone formation was observed among different groups. Besides the osteoconductive effect, Group A with smallest pore size also had the best mechanical properties in vivo at 12 weeks. We demonstrate that pore size has a significant effect on the osteoconductivity and mechanical properties of calcium phosphate cement porous scaffold in vivo. Small pore size favors the bone formation in the early stage and may be more suitable for repairing segmental bone defect in vivo.

Influence of polymeric additives on the cohesion and mechanical properties of calcium phosphate cements.

To expand the clinical applicability of calcium phosphate cements (CPCs) to load-bearing anatomical sites, the mechanical and setting properties of CPCs need to be improved. Specifically, organic additives need to be developed that can overcome the disintegration and brittleness of CPCs. Hence, we compared two conventional polymeric additives (i.e. carboxylmethylcellulose (CMC) and hyaluronan (HA)) with a novel organic additive that was designed to bind to calcium phosphate, i.e. hyaluronan–bisphosphonate (HABP). The unmodified cement used in this study consisted of a powder phase of α-tricalcium phosphate (α-TCP) and liquid phase of 4 % NaH2PO4·2H2O, while the modified cements were fabricated by adding 0.75 or 1.5 wt% of the polymeric additive to the cement. The cohesion of α-TCP was improved considerably by the addition of CMC and HABP. None of the additives improved the compression and bending strength of the cements, but the addition of 0.75 % HABP resulted into a significantly increased cement toughness as compared to the other experimental groups. The stimulatory effects of HABP on the cohesion and toughness of the cements is hypothesized to derive from the strong affinity between the polymer-grafted bisphosphonate ligands and the calcium ions in the cement matrix.