Calcium Phosphate Cement Formulation Research Articles

Tunable calcium phosphate cement formulations for predictable local release of doxycycline

Background Osteomyelitis is a bacterial infection, which leads to bone loss. Local treatment focuses on elimination of bacteria, which is preferable for simultaneous management of the bone defect after sequestrectomy and bone reconstruction in one-stage treatment of osteomyelitis. Calcium phosphate cements (CPCs) have attracted increased attention as bone substitute material because of their injectability and in situ self-setting properties, which allow for minimally invasive surgical procedures and local drug delivery.Methods We herein established a system to achieve different release profiles of the antibiotic drug doxycycline from CPC by finetuning their formulation. These CPC formulations were generated via facile addition of hydrolytically degrading PLGA particles, varying doses of doxycycline, and addition of the lubricant CMC.Results The CPC formulations exhibited appropriate handling properties in terms of injectability and setting time. Furthermore, doxycycline release profiles showed an adequate burst release followed by a cumulative release of up to 100% over a period of 8 weeks. Importantly, the released doxycycline retained its antibacterial activity against Staphylococcus aureus, the major pathogen causing osteomyelitis. Using an in vivo implantation model, antibacterial efficacy was demonstrated by a rapid decrease of inoculated S. aureus at the CPC surface and within surrounding tissues.Conclusions Our data show the versatility of the CPC system toward local antibacterial therapy, extending its application beyond bone substitution.

Tunable Calcium Phosphate Cement Formulations for Predictable Local Release of Doxycycline

Tunable Calcium Phosphate Cement Formulations for Predictable Local Release of Doxycycline

Characterization and multiscale modeling of novel calcium phosphate composites containing hydroxyapatite whiskers and gelatin microspheres

In this study, novel calcium phosphate cement (CPC) composites were prepared by simultaneous incorporation of porogenic crosslinked gelatin microspheres (GMs) and reinforcing hydroxyapatite whiskers (HAWs) into the CPC matrix and the effects of the mentioned additives on the compositional characteristics, phase evolution, setting time, microstructure and mechanical properties of the CPC matrix, were thoroughly investigated. Simulation techniques and multiscale modeling were also employed to predict and compare mechanical properties of the composite formulations with those of real mechanical tests. For this purpose, composite CPCs of varying compositions were prepared by concurrent addition of GMs (5, 10 wt %) and HAWs (5–30 wt %) to the typical apatitic CPC composed of equimolar mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA). Morphological observations by SEM confirmed proper dispersion of the additive materials in the CPC matrix. The results of the compositional evaluation of the composites by FTIR and XRD also revealed that the additives preferably didn’t exhibit a considerable inhibitive effect on the HA conversion during the composite CPC setting process. Porosity measurements approved that GMs could act as porogenic materials which introduced an increased total porosity of up to ∼69% to the structure of composites. The CPC sample and the composite cements also exhibited considerable specific surface area of 12.99 and 4.32–8.20 m 2 /g, respectively. Moreover, the results of compressive mechanical testing showed that the CPC control and the composites had a compressive strength of 28.1, 9.5–29.4 MPa and Young modulus of 3860 and 515–2630 MPa, respectively. However, in terms of mechanical and microstructural features, the composites containing 10 wt % of HAWs exhibited the most preferable characteristics. The mechanical results of the multiscale modeling method were also in the same range of those obtained by experimental compressive tests. Such finding was more notable for the composites with lower content of HAWs (5 and 10 wt %), when the predicted mechanical values for such samples were more than 80% accurate. In-vitro cellular tests also showed that the additives (GMs and HAWs) improved biological response of the composites, with 10 wt % of GMs and HAWs as the optimal amount. Nevertheless, depending on the bone graft requirements and the needed compromise between porosity and mechanical properties; the optimum composite can be chosen. • Successful synthesis of Gelatin Microspheres (GMs) and Hydroxyapatite whiskers (HAWs). • Incorporation of GMs and HAWs into the calcium phosphate cement (CPCs). • Designing novel composite CPC formulations with different amounts of GMs and HAWs. • Thorough characterization of CPC composites to determine optimum formulations. • Observation of reinforcing and porogenic roles by HAWs and GMs, respectively.

In Vitro Release of Bioactive Bone Morphogenetic Proteins (GDF5, BB-1, and BMP-2) from a PLGA Fiber-Reinforced, Brushite-Forming Calcium Phosphate Cement.

Bone regeneration of sheep lumbar osteopenia is promoted by targeted delivery of bone morphogenetic proteins (BMPs) via a biodegradable, brushite-forming calcium-phosphate-cement (CPC) with stabilizing poly(l-lactide-co-glycolide) acid (PLGA) fibers. The present study sought to quantify the release and bioactivity of BMPs from a specific own CPC formulation successfully used in previous in vivo studies. CPC solid bodies with PLGA fibers (0%, 5%, 10%) containing increasing dosages of GDF5, BB-1, and BMP-2 (2 to 1000 µg/mL) were ground and extracted in phosphate-buffered saline (PBS) or pure sheep serum/cell culture medium containing 10% fetal calf serum (FCS; up to 30/31 days). Released BMPs were quantified by ELISA, bioactivity was determined via alkaline phosphatase (ALP) activity after 3-day exposure of different osteogenic cell lines (C2C12; C2C12BRlb with overexpressed BMP-receptor-1b; MCHT-1/26; ATDC-5) and via the influence of the extracts on the expression of osteogenic/chondrogenic genes and proteins in human adipose tissue-derived mesenchymal stem cells (hASCs). There was hardly any BMP release in PBS, whereas in medium + FCS or sheep serum the cumulative release over 30/31 days was 11–34% for GDF5 and 6–17% for BB-1; the release of BMP-2 over 14 days was 25.7%. Addition of 10% PLGA fibers significantly augmented the 14-day release of GDF5 and BMP-2 (to 22.6% and 43.7%, respectively), but not of BB-1 (13.2%). All BMPs proved to be bioactive, as demonstrated by increased ALP activity in several cell lines, with partial enhancement by 10% PLGA fibers, and by a specific, early regulation of osteogenic/chondrogenic genes and proteins in hASCs. Between 10% and 45% of bioactive BMPs were released in vitro from CPC + PLGA fibers over a time period of 14 days, providing a basis for estimating and tailoring therapeutically effective doses for experimental and human in vivo studies.

Multimodal porogen platforms for calcium phosphate cement degradation.

Calcium phosphate cements (CPCs) represent excellent bone substitute materials due to their biocompatibility and injectability. However, their poor degradability and lack of macroporosity limits bone regeneration. The addition of poly(d,l‐lactic‐co‐glycolic acid) (PLGA) particles improves macroporosity and therefore late stage material degradation. CPC degradation and hence, bone formation at an early stage remains challenging, due to the delayed onset of PLGA degradation (i.e., after 2–3 weeks). Consequently, we here explored multimodal porogen platforms based on sucrose porogens (for early pore formation) and PLGA porogens (for late pore formation) to enhance CPC degradation and analyzed mechanical properties, dynamic in vitro degradation and in vivo performance in a rat femoral bone defect model. Porogen addition to CPC showed to decrease compressive strength of all CPC formulations; transition of the crystal phase upon in vitro incubation increased compressive strength. Although dynamic in vitro degradation showed rapid sucrose dissolution within 1 week, no additional effects on CPC degradation or bone formation were observed upon in vivo implantation. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1713–1722, 2019.

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.

Visualization of calcium phosphate cement in teeth by zero echo time 1 H MRI at high field.

1 H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high-field ZTE imaging to enable the visualization of a new CPC formulation implanted in teeth and to apply this in the assessment of its decomposition in vivo. CPC was implanted in three human and three goat teeth ex vivo and in three goat teeth in vivo. An ultrashort echo time (UTE) sequence with multiple flip angles and echo times was applied at 11.7 T to measure T1 and T2 * values of CPC, enamel and dentin. Teeth with CPC were imaged with an optimized ZTE sequence. Goat teeth implanted with CPC in vivo were imaged after 7 weeks ex vivo. T2 * relaxation of implanted CPC, dentin and enamel was better fitted by a model assuming a Gaussian rather than a Lorentzian distribution. For CPC and human enamel and dentin, the average T2 * values were 273 ± 19, 562 ± 221 and 476 ± 147 μs, respectively, the average T2 values were 1234 ± 27, 963 ± 151 and 577 ± 41 μs, respectively, and the average T1 values were 1065 ± 45, 972 ± 40 and 903 ± 7 ms, respectively. In ZTE images, CPC had a higher signal-to-noise-ratio than dentin and enamel because of the higher water content. Seven weeks after in vivo implantation, the CPC-filled lesions showed less homogeneous structures, a lower T1 value and T2 * separated into two components. MRI by ZTE provides excellent contrast for CPC in teeth and allows its decomposition to be followed.

Elastic properties and strain-to-crack-initiation of calcium phosphate bone cements: Revelations of a high-resolution measurement technique

Calcium phosphate cements (CPCs) should ideally have mechanical properties similar to those of the bone tissue the material is used to replace or repair. Usually, the compressive strength of the CPCs is reported and, more rarely, the elastic modulus. Conversely, scarce or no data are available on Poisson's ratio and strain-to-crack-initiation. This is unfortunate, as data on the elastic response is key to, e.g., numerical model accuracy. In this study, the compressive behaviour of brushite, monetite and apatite cements was fully characterised. Measurement of the surface strains was done using a digital image correlation (DIC) technique, and compared to results obtained with the commonly used built-in displacement measurement of the materials testers. The collected data showed that the use of fixed compression platens, as opposed to spherically seated ones, may in some cases underestimate the compressive strength by up to 40%. Also, the built-in measurements may underestimate the elastic modulus by up to 62% as compared to DIC measurements. Using DIC, the brushite cement was found to be much stiffer (24.3 ± 2.3GPa) than the apatite (13.5 ± 1.6GPa) and monetite (7.1 ± 1.0GPa) cements, and elastic moduli were inversely related to the porosity of the materials. Poisson's ratio was determined to be 0.26 ± 0.02 for brushite, 0.21 ± 0.02 for apatite and 0.20 ± 0.03 for monetite. All investigated CPCs showed low strain-to-crack-initiation (0.17–0.19%). In summary, the elastic modulus of CPCs is substantially higher than previously reported and it is concluded that an accurate procedure is a prerequisite in order to properly compare the mechanical properties of different CPC formulations. It is recommended to use spherically seated platens and measuring the strain at a relevant resolution and on the specimen surface.

Tuning the degradation rate of calcium phosphate cements by incorporating mixtures of polylactic-co-glycolic acid microspheres and glucono-delta-lactone microparticles.

Calcium phosphate cements (CPCs) are frequently used as synthetic bone graft materials in view of their excellent osteocompatibility and clinical handling behavior. Hydroxyapatite-forming CPCs, however, degrade at very low rates, thereby limiting complete bone regeneration. The current study has investigated whether degradation of apatite-forming cements can be tuned by incorporating acid-producing slow-resorbing poly(D,L-lactic-co-glycolic) acid (PLGA) porogens, fast-resorbing glucono-delta-lactone (GDL) porogens, or mixtures thereof. The physicochemical, mechanical, and degradation characteristics of these CPC formulations were systematically analyzed upon soaking in phosphate-buffered saline (PBS). In parallel, various CPC formulations were implanted intramuscularly and orthotopically on top of the transverse process of goats followed by analysis of the soft tissue response and bone ingrowth after 12 weeks. In vitro degradation of GDL was almost completed after 2 weeks, as evidenced by characterization of the release of gluconic acid, while PLGA-containing CPCs released glycolic acid throughout the entire study (12 weeks), resulting in a decrease in compression strength of CPC. Extensive in vitro degradation of the CPC matrix was observed upon simultaneous incorporation of 30% PLGA-10% GDL. Histomorphometrical evaluation of the intramuscularly implanted samples revealed that all CPCs exhibited degradation, accompanied by an increase in capsule thickness. In the in vivo goat transverse process model, incorporation of 43% PLGA, 30% PLGA-5% GDL, and 30% PLGA-10% GDL in CPC significantly increased bone formation and resulted in higher bone height compared with both 10% GDL and 20% GDL-containing CPC samples.

Calcium phosphate cement as an alternative for formocresol in primary teeth pulpotomies

Formocresol remains to be the preferred medicament in pulpotomy, despite the concerns regarding tissue devitalization and systemic toxicity. Several materials were used as alternatives, but none proved significantly advantageous. Of recent, calcium phosphate cement (CPC) has been projected as an ideal pulpotomy material considering its tissue compatibility and dentinogenic properties. This study explores the suitability of a CPC formulation for pulpotomy, in comparison with formocresol. This comparative case study included 10 children (8-12 age group) having a pair of non-carious primary canines (both maxillary and mandibular) posted for extraction. Pulpotomy was performed with CPC in the right canines and formocresol in the left and sealed with IRM ® (Dentsply). The teeth were extracted at 70 ± 5 days and sectioned and stained for the histopathological evaluation. Parameters such as pulpal inflammation, tissue reaction to material, dentine bridge formation, location of dentine bridge, quality of dentine formation in bridge, and connective tissue in bridge etc. were evaluated. The histological assessment after 70 days showed no statistically significant difference between the two groups in any of the parameters. However, CPC gave more favorable results in pulpal inflammation, with a lower score of 1.6 against 2.6 for formocresol. CPC samples showed better formation of dentine bridge in quantity and quality. The mean scores for CPC for the extent of dentine bridge formation, quality of dentine bridge and connective tissue in the bridge, were 2.0, 1.4, and 1.2 respectively, whereas the corresponding values for formocresol were 0.8, 0.2, and 1.0. CPC is more compatible to pulp tissues than formocresol and it shows good healing potential. CPC is capable of inducing dentine formation without an area of necrosis.

Properties of injectable ready-to-use calcium phosphate cement based on water-immiscible liquid

Calcium phosphate cements (CPCs) are highly valuable materials for filling bone defects and bone augmentation by minimal invasive application via percutaneous injection. In the present study some key features were significantly improved by developing a novel injectable ready-to-use calcium phosphate cement based on water-immiscible carrier liquids. A combination of two surfactants was identified to facilitate the targeted discontinuous exchange of the liquid for water after contact with aqueous solutions, enabling the setting reaction to take place at distinct ratios of cement components to water. This prolonged the shelf life of the pre-mixed paste and enhanced reproducibility during application and setting reactions. The developed paste technology is applicable for different CPC formulations. Evaluations were performed for the formulation of an α-TCP-based CPC as a representative example for the preparation of injectable pastes with a powder-to-carrier liquid ratio of up to 85:15. We demonstrate that the resulting material retains the desirable properties of conventional CPC counterparts for fast setting, mechanical strength and biocompatibility, shows improved cohesion and will most probably show a similar degree of resorbability due to identical mineral structure of the set products.

Polymeric additives to enhance the functional properties of calcium phosphate cements

The vast majority of materials used in bone tissue engineering and regenerative medicine are based on calcium phosphates due to their similarity with the mineral phase of natural bone. Among them, calcium phosphate cements, which are composed of a powder and a liquid that are mixed to obtain a moldable paste, are widely used. These calcium phosphate cement pastes can be injected using minimally invasive surgery and adapt to the shape of the defect, resulting in an entangled network of calcium phosphate crystals. Adding an organic phase to the calcium phosphate cement formulation is a very powerful strategy to enhance some of the properties of these materials. Adding some water-soluble biocompatible polymers in the calcium phosphate cement liquid or powder phase improves physicochemical and mechanical properties, such as injectability, cohesion, and toughness. Moreover, adding specific polymers can enhance the biological response and the resorption rate of the material. The goal of this study is to overview the most relevant advances in this field, focusing on the different types of polymers that have been used to enhance specific calcium phosphate cement properties.

New approaches for the local prevention of osteoporotic fractures

ABSTRACTCombining Bisphophonates (BPs) and Calcium Phosphate Cement (CPC) to form a new medical device for the local treatment of Osteoporosis is a promising challenge. Our formulation was optimized from an apatitic-type CPC and we have shown that the best solution consists in introducing the bisphosphonate (Alendronate) in the calcium deficient apatite (CDA), a solid component of the cement, through a chemical exchange reaction. The cement obtained was characterized by 31P NMR and high frequency impedance for monitoring the CPC setting. The presence of Alendronate in the cement was also demonstrated by 31P NMR which has been also used to characterize the chemical transformation of α-TCP (main component of the apatitic cement) during the setting process. BP absorption/desorption experiments have been realized on cement blocks, under continuous flow condition, to model the release profile of the Alendronate. In vivo experiments showed promising results in terms of resorbability of the Alendronate–loaded cement while promoting new bone formation. The same methodology is considered to introduce gallium, a potential inhibitor of osteoclastic resorption, in a CPC formulation. First experiments have shown that gallium can be incorporated in calcium phosphate ceramics (i.e. β-TCP) where gallium is part of the network.

Fiber‐reinforced calcium phosphate cement formulations for cranioplasty applications: A 52‐week duration preclinical rabbit calvaria study

The in vivo tissue response to a newly developed fiber-reinforced calcium phosphate cement (CPC) formulation was assessed using a well-established rabbit calvarial defect model. Bilateral subcritical sized (8-mm diameter) defects were surgically created in the parietal bones of each rabbit (a total of 48 rabbits), and randomized to be filled with either the new fiber-reinforced formulation, a conventional CPC (positive control), or left unfilled (negative control). The implant sites were subsequently retrieved after 12, 24, and 52 weeks postsurgery. Each specimen, including the parietal bone craniotomy and underlying brain, were recovered at necropsy and the tissue responses were assessed by histology. The resulting histological slides indicated that there was no evidence of severe inflammatory responses or osteolysis. The data showed new dural and pericranial bone formation along the implants, as well as excellent bone-to-implant interfaces in all of the CPC-filled defects. These results suggest that the biologic response to the new fiber-reinforced CPC formulations and conventional nonreinforced CPC are very similar, and both demonstrate excellent biocompatibility as well as an overall osteophylic response.

Cytotoxicity, calcium release, and pH changes generated by novel calcium phosphate cement formulations

Few published studies describe the biological properties of calcium phosphate cements (CPCs) for dental applications. We measured several biologically relevant properties of 3 CPCs over an extended (8 wk) interval. Monocalcium phosphate, calcium oxide, and synthetic hydroxyapatite were combined with either modified polyacrylic acid, light-activated modified polyalkenoic acid, or 35% w/w polymethyl vinyl ether maleic acid to obtain Types I, II, and III CPCs, respectively. Set cements were placed in direct contact with L929 fibroblasts for up to 8 weeks. Media Ca(+2) and pH were determined by atomic absorption spectroscopy and pH electrode respectively. Cell mitochondrial function was measured by MTT assay. Type I cements suppressed mitochondrial activity > 90% (vs. Teflon controls), but significantly (p < 0.05) improved to control levels over 8 weeks. Type II cements suppressed mitochondrial activity > 90% at all times. Type III cements elevated mitochondrial activity significantly after 7 wks. The pH profiles approached neutrality by 24 h, and all cements released calcium into the storage medium at all periods (24 h - 8 wk). We concluded that several types of cements had long-term biological profiles that show promise for dental applications.

TTCP-DCPA Based Calcium Phosphate Cements Containing Hybrid Microparticles as Drug Carriers

In recent years, considerable attention has been focused on the development of new composite materials for application as drug delivery systems. In this field, calcium phosphate cements (CPCs) are often employed as support to delivery of drugs, but their behavior has some drawback related to the so-called burst effect. The aim of this work was to develop new CPCs formulations from synthesized tetracalcium phosphate (TTCP), dicalcium phosphate anhydrous TTCP and drug-containing hybrid microparticles (DCHM). The main function of these DCHM is providing nuclei of high concentration of drugs into the CPCs. The DCHM were synthesized via the sol-gel method from a bridged precursor of the type (H3CO)3 – Bridge – (OCH3)3 and aspirin (AS) as model drug. The inorganic polycondensation reached 89.5 % as calculated by 29Si NMR. The analysis by small angle X-ray scattering (SAXS) reveled a short range structural ordering in the DCHM at molecular level. Effective incorporation of AS inside the microspheres was detected by FTIR spectroscopy. In vitro tests of DCHM according to ISO 10993-5 revealed non-cytotoxic behavior. Four CPCs formulations containing 0, 1, 5 and 10 wt % of DCHM, were evaluated. The presence of DCHM did not modify neither the degree of conversion to low-crystallinity HA nor the measured setting times of the CPCs, however, the amount of incorporated microparticles considerably affected the degree of porosity (macropores of 200 µm) and interconnectivity of the cement matrix.

Adhesion of a Novel Calcium Phosphate Cement to Cortical Bone and Several Common Biomaterials

In this study, we have shown that by incorporating pyrophosphoric acid into a brushite cement system, it is possible to produce a cement that exhibits adhesive tensile strengths with cortical bone, alumina, sintered hydroxyapatite and 316L stainless steel of 700 kPa. To our knowledge, this is the first report of a calcium phosphate cement formulation that exhibits such adhesive properties without the addition of an organic additive. The production of a bond between medical prostheses and bone may further widen the field of application of calcium phosphate cements, additionally the adhesive nature of the calcium phosphate cement may be a desirable ‘handling characteristic’ during reconstructive surgery.

Development of a fully injectable calcium phosphate cement for orthopedic and dental applications

A study on the development of a fully injectable calcium phosphate cement for orthopedic and dental applications is presented. The paper describes its characteristic properties including results of biocompatibility studies.A conventional two-component calcium phosphate cement formulation (having a powder part containing dry mixture of acidic and basic calcium phosphate particles and a liquid part containing phosphate solution) is modified with a biocompatible gelling agent, to induce flow properties and cohesion. The quantity of the gelling agent is optimized to get a viscous paste, which is smoothly injectable through an 18-gauge needle, with clinically relevant setting parameters.The new formulation has a setting time of 20 min and a compressive strength of 11 MPa. The X-ray diffraction, Fourier transform infrared spectrometry, and energy dispersive electron microprobe analyses showed the phase to be hydroxyapatite, the basic bone mineral. Scanning electron microscopy revealed a porous structure with particle sizes of a few micrometers. The cement did not show any appreciable dimensional or thermal change during setting. The injectability is estimated by extruding through needle and the cohesive property is assessed by water contact method. The cement passed the in vitro biocompatibility screening (cytotoxicity and haemolysis) tests.

The exothermal behavior in the hydration process of calcium phosphate cement

The exothermal behavior in the hydration process of calcium phosphate cement (CPC) and their effect factors were investigated systematically. One CPC formulation is composed of tetracalcium phosphate (TECP) and dicalcium phosphate anhydrous (DCPA), and its hydration reaction is an exothermic reaction. Hydration includes five processes, namely, the start, induction, acceleration, deceleration and the terminating process. The introduction of hydroxyapatite (HAP) as crystal seed shortens induction and advances on the reaction peak position, which resulted from the introduction of crystal seed that reduced the activation energy of heterogeneous nucleation. The increase in temperature not only makes the reaction advance but also enlarges it. The activation energy of the hydration reaction is 176 kJ/mol by calculation. The particle size of the raw material and the ratio of calcium to phosphate in the specimen have large effects on the hydration process. Decrease in particle size of TECP and in the ratio of calcium to phosphate resulted in marked acceleration of reaction and made the reaction peak advance evidently, but the effect of particle size of DCPA is not so remarkable. Based on the heat liberation in the hydration of CPC specimens taking Ca/P as 1.5 and 1.67, the standard mole enthalpies of formation of TECP and calcium-deficient hydroxyapatite are −5908 and −11119 kJ mol −1, respectively.

Structural characterization of phosphorylated chitosan and their applications as effective additives of calcium phosphate cements

Chitosan was phosphorylated by P 2O 5 in methanesulfonic acid and the product as water-soluble phosphorylated chitosan (P-chitosans) was then characterized by phosphorus elemental analysis, IR and 31P-NMR spectroscopy. Two calcium phosphate cement (CPC) systems, i.e. (1) monocalcium phosphate monohydrate (MCPM) and calcium oxide (CaO) in 1 mphosphate buffer (pH=7.4) and (2) dicalcium phosphate dihydrate (DCPD) and calcium hydroxide [Ca(OH) 2] in 1 m Na 2HPO 4 solution, were chosen to improve their mechanical properties by the addition of water-soluble P-chitosans with various values for molecular weight, degree of deacetylation (DD) and degree of substitution (DS). The results show that the compressive strength (CS) and Young's modulus of both CPC formulations after setting were obviously increased and setting time was slightly prolonged by adding water-soluble P-chitosan to the liquid phases. When a suitable amount of P-chitosan was used, two improved CPC formulations were obtained with much better mechanical properties while the setting times were not longer than 15 min. The enhancement of compressive strength was due to high Ca 2+-binding ability of phosphorylated chitosan, which could tightly bind the newly formed hydroxyapatite (HA) particles together by polymeric chains. It was noted that excessive addition of P-chitosan would lead to slow setting or no setting at all. The hardened CPC samples containing P-chitosan were characterized via X-ray diffraction spectra and scanning electron microscopy. Their leaching experiment was also carried out. The results indicated that P-chitosan-forced calcium phosphate cements have some good characteristics for clinical applications.