Tricalcium Phosphate Bioceramics Research Articles

Synthesis, characterization and cell response of silicon/gallium co-substituted tricalcium phosphate bioceramics

Synthesis, characterization and cell response of silicon/gallium co-substituted tricalcium phosphate bioceramics

Conjunction of gallium doping and calcium silicate mediates osteoblastic and osteoclastic performances of tricalcium phosphate bioceramics

Gallium-containing biomaterials are considered promising for reconstructing osteoporotic bone defects, owing to the potent effect of gallium on restraining osteoclast activities. Nevertheless, the gallium-containing biomaterials were demonstrated to disturb the osteoblast activities. In this study, tricalcium phosphate (TCP) bioceramics were modified by gallium doping in conjunction with incorporation of calcium silicate (CS). The results indicated that the incorporation of CS promoted transition of β-TCP to α-TCP, and accelerated densification process, but did not improve the mechanical strength of bioceramics. The silicon released from the composite bioceramics diminished the inhibition effect of released gallium on osteoblast activities, and maintained its effect on restraining osteoclast activities. The TCP-based bioceramics doped with 2.5 mol% gallium and incorporated with 10 mol% CS are considered suitable for treating the bone defects in the osteoporotic environment.

Speedy bioceramics: Rapid densification of tricalcium phosphate by ultrafast high-temperature sintering

Due to unique osteogenic properties, tricalcium phosphate (TCP) has gained relevance in the field of bone repair. The development of novel and rapid sintering routes is of particular interest since TCP undergoes to high-temperature phase transitions and is widely employed in osteoconductive coatings on thermally-sensitive metal substrates.In the present work, TCP bioceramics was innovatively obtained by Ultrafast High-temperature Sintering (UHS). Ca-deficient hydroxyapatite nano-powder produced by mechanochemical synthesis of mussel shell-derived calcium carbonate was used to prepare the green samples by uniaxial pressing. These were introduced within a graphite felt which was rapidly heated by an electrical current flow, reaching heating rates exceeding 1200 °C min−1. Dense (> 93%) ceramics were manufactured in less than 3 min using currents between 25 and 30 A. Both β and α-TCP were detected in the sintered components with proportions depending on the applied current. Preliminary tests confirmed that the artifacts do not possess cytotoxic effects and possess mechanical properties similar to conventionally sintered materials. The overall results prove the applicability of UHS to bioceramics paving the way to new rapid processing routes for biomedical components.

Experimental substantiation of the use of hydroxyapatite — tricalcium phosphate bioceramics for replacing bone defects after tumor removal

Recently, bioactive ceramics based on hydroxyapatite (HAP) and tricalcium phosphate (TCP) have been preferred as implants in bone engineering. To study bone regeneration under conditions of filling metaphyseal defects with the original HAP-TCP composition. The experiment was carried out on inbred rats, the observation period was 2, 4, 8weeks. Morphological studies were carried out using light and electron microscopy. In the dynamics of observation at 2, 4and 8weeks, a gradual arrangement of osteoclasts and osteoblasts on the surface of HAP-TCP was recorded, which indicates its high biocompatibility with bone tissue. During the experiment, the processes of resorption of implants, mineralization, proliferation of cellular elements of collagen and osteogenesis (osteoblasts and osteoclasts) and the formation of mature bone tissue were recorded. Experimental studies of plastic bone defects proved the presence of the osteoinductive and osteointegrative effect of HAP-TCP composition, which contributes to a more dynamic uncomplicated course of reparative osteogenesis.

FDM 3D Printed Composites for Bone Tissue Engineering Based on Plasticized Poly(3-hydroxybutyrate)/poly(d,l-lactide) Blends.

Tissue engineering is a current trend in the regenerative medicine putting pressure on scientists to develop highly functional materials and methods for scaffolds’ preparation. In this paper, the calibrated filaments for Fused Deposition Modeling (FDM) based on plasticized poly(3-hydroxybutyrate)/poly(d,l-lactide) 70/30 blend modified with tricalcium phosphate bioceramics were prepared. Two different plasticizers, Citroflex (n-Butyryl tri-n-hexyl citrate) and Syncroflex (oligomeric adipate ester), both used in the amount of 12 wt%, were compared. The printing parameters for these materials were optimized and the printability was evaluated by recently published warping test. The samples were studied with respect to their thermal and mechanical properties, followed by biological in vitro tests including proliferation, viability, and osteogenic differentiation of human mesenchymal stem cells. According to the results from differential scanning calorimetry and tensile measurements, the Citroflex-based plasticizer showed very good softening effect at the expense of worse printability and unsatisfactory performance during biological testing. On the other hand, the samples with Syncroflex demonstrated lower warping tendency compared to commercial polylactide filament with the warping coefficient one third lower. Moreover, the Syncroflex-based samples exhibited the non-cytotoxicity and promising biocompatibility.

Ethylene vinyl acetate as a binder for additive manufacturing of tricalcium phosphate bio-ceramics

Tricalcium phosphate (TCP) ceramic scaffolds were made by the fused filament fabrication (FFF) using different grades of Ethylene vinyl acetate (EVA) as a thermoplastic binder. Stearic acid was studied as a processing aid. A wide range of rheological properties, shaping and debinding behavior could be observed with feedstocks made with different EVA grades. The addition of stearic acid affects flexibility of the solid filaments, the viscosity of feedstocks, and causes a pronounced yield stress behavior. These effects are strongly dependent on the molecular weight of the EVA and influence the printing process and shape stability during the debinding process. EVA binder system works well for thin and small parts, made with nozzle sizes below 0.4 mm, whereas samples made by thicker nozzle size form defects during debinding process. TCP scaffold structures with fin struts of 0.27 mm and partition wall thickness of 0.25 mm and a layer thickness of 0.20 mm could be successfully shaped, debinded and sintered. Excellent fusion between the different layers was achieved, since no defects at the interface could be detected.

In vitro investigation of the growth of hydroxyapatite and proliferation of human cell lines on the sol gel derived diopside co-substituted tricalcium phosphate bioceramics

Sol-gel derived bioceramic samples with the composition formula x(CaO.MgO.2SiO2).(100-x)3CaO.P2O5 where x = 0, 10, 20, 30 and 40 mass% have been prepared in the laboratory. Diopside (CaO.MgO.2SiO2) co-substituted tricalcium phosphate (3CaO.P2O5) bioceramics are speculated to be successful bone repair materials for clinical applications due to improved bone bonding ability and bioresorbability properties. Authors have employed x-ray diffraction, Raman spectroscopy, field emission scanning electron microscopy along with energy dispersive spectroscopy, hardness testing and cell culture studies during the investigations. X-ray diffraction spectra demonstrated the formation of crystalline phases of diopside, merwinite and whitlockite in the samples and Raman spectra shows the presence of phosphate species in the orthophosphate environment. In vitro hydroxyapatite forming ability in simulated body fluid has been investigated by x-ray diffraction, Raman and field emission scanning electron microscopy techniques for time durations varying between day 1 to day 12 and results demonstrated that hydroxyapatite layer has developed from day 1 in sample with composition 40 mass% tricalcium phosphate and 60 mass% diopside. Pure diopside has shown the best hardness value. Although, 10 mass% tricalcium phosphate and 90 mass% diopside composition has shown the slower rate for growth of hydroxyapatite but it has shown the best cell viability values for human cell line. Results indicate that growth rate of hydroxyapatite is composition as well as sample synthesis technique dependent.

Effect of Pressure and Temperature in Solid State Sintering Approach Producing Porous Tricalcium Phosphate Bioceramics

Porous Tricalcium Phosphate (TCP) is recognized as a good biomaterial having excellent biocompatibility, biodegrability and bioresorbability. Some of the techniques to produce porous β-TCP, are replica technique (polymeric sponge method), sacrificial template method and direct forming method, however, these methods are complicated and can be costly. In this study, solid state sintering was adopted to form porous TCP as a new approach to overcome these problems. TCP bioceramic was prepared by mixing calcium hydrogen phosphate dihydrate and calcium carbonate. The powders were pressed into pellet form with four different pressures; 10, 20, 30 and 40 MPa. Then, the pellets were sintered at 1100°C to 1400°C and subsequently characterized by X-ray diffraction (XRD), density and porosity measurement, diametral tensile strength test (DTS) and scanning electron microscopy (SEM) evaluation. β-TCP phase was maintained at 1100°C and 1200°C whilst α-TCP phase had formed as second phase above 1300°C. The highest apparent porosity (60.93%) was obtained at 10 MPa and 1100°C sintering temperature, with the density of 1.12 g/cm3. The DTS values were in the range of 0.31 to 3.78 MPa in with lower DTS values were obtained at low compaction pressure and sintering temperature. Interconnected pores with high level porosity were observed at the fracture surfaces of the sintered pellets. Intraporosity was also observed. In conclusion, TCP bioceramics with interconnected pores were produced via solid state reaction; however, more work is required to improve the level of porosity.

In vitro study of the proliferation and growth of human fetal osteoblasts on Mg and Si co-substituted tricalcium phosphate ceramics.

The objective of this work was to study the feasibility of the solid state sintering, a conventional ceramic processing method, to obtain Mg and Si co-substituted tricalcium phosphate bioceramics and composites containing diopside. A series of new Ca3 (PO4 )2 based ceramics has been prepared from attrition milled mixtures of synthetic Ca3 (PO4 )2 and CaMg(SiO3 )2 powders, isostatically pressed and sintered at 1250-1300°C. Materials containing 0, 1, and 5 wt % of CaMg(SiO3 )2 were constituted by β + α - Ca3 (PO4 )2 solid solutions while the material containing 60 wt % of CaMg(SiO3 )2 was a constituted by β- Ca3 (PO4 )2 and CaMg(SiO3 )2 . The biological responses of the developed ceramics were studied in vitro using human fetal osteoblast cultures. Culture times ranged from 1 to 21 days. The new family of materials promotes the adhesion and proliferation of human osteoblasts cultured onto their surface forming a monolayer and showing a normal morphology. The results of the MTT and Alamar Blue assays showed that the soluble components extracted from the Mg/Si- co-substituted Ca3 (PO4 )2 and the Ca3 (PO4 )2 -CaMg(SiO3 )2 composite were noncytotoxic. The specimens with diopside exhibited a better in vitro behavior which is attributed to the release of Si and Mg ions to the culture medium, enhancing the activity of cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2266-2275, 2017.

Effect of Mg and Si co-substitution on microstructure and strength of tricalcium phosphate ceramics

Magnesium and silicon co-doped tricalcium phosphate (TCP) ceramics with compositions corresponding to 0, 5 and 10wt% CaMg(SiO3)2 in the system Ca3(PO4)2–CaMg(SiO3)2 were obtained by conventional sintering of compacted mixtures of Ca3(PO4)2, MgO, SiO2 and CaCO3 powders at temperatures between 1100 and 1450°C. Microstructural analyses were performed by X-ray diffraction and field emission scanning electron microscopy with energy dispersive spectroscopy. Major phases in the obtained ceramics were β- or α+β-tricalcium phosphate containing Mg and Si in solid solution. Certain amounts of liquid were formed during sintering depending on composition and temperature. There were found significant differences in distributions of strength determined by the diametral compression of disc tests (DCDT). Failure strengths were controlled by microstructural defects associated with phase development.Mg and Si additions were found to be effective to improve densification and associated strength of TCP bioceramics due to the enhancement of sintering by the low viscosity liquids formed. The highest density and strength were obtained for the TCP ceramic containing 5wt% CaMg(SiO3)2 sintered at 1300°C. Cracking and porosity increased at higher temperatures due to grain growth and swelling.

Surface Modification of Biomaterials for Conjugation with Human Fetal Osteoblasts

Surface functionalization of hydroxyapatite (HA) and beta-tricalcium phosphate (TCP) bioceramics with chemical ligands containing a pyrrogallol moiety was developed to improve the adhesion of bone cell precursors to the biomaterials. Fast and biocompatible copper-free click reaction with azido-modified human fetal osteoblasts resulted in improved cell binding to both HA and TCP bioceramics, opening the way for using this methodology in the preparation of cell-engineered bone implants.

Ordered HAp nanoarchitecture formed on HAp-TCP bioceramics by "nanocarving" and mineralization deposition and its potential use for guiding cell behaviors.

Nanotopographic modification is one of the effective strategies to guide cell behaviors and improve the bioactivity of biomaterials. Hydrothermal synthesis has been preferably used to produce low-dimensional nanostructured materials due to its simplicity, cost-effectiveness and controllability of crystal morphologies. However, assembling low dimensional nanosized units into an integrated and well-ordered high dimensional structure (2D film and 3D architecture) on biomaterials or biomedical devices remains a big challenge. In this study, we designed a novel substrate-dependent hydrothermal strategy to produce a biocompatible hydroxyapatite (HAp) nanorod array structure and well-organized nano-sheet architecture on a HAp-tricalcium phosphate (TCP) bioceramic - one of the widely used biomaterials in bone tissue engineering. The nanorod array structure resulted from the "nanocarving" process in the reaction with buffered solutions, while the well-organized nano-sheet architecture was formed by the subsequent mineralization deposition on the nanorod array structure. Both "nanocarving" and mineralization deposition processes are strongly dependent on the phase composition of the HAp-TCP substrates and influenced by the Ca and P ion concentrations of the buffer used. Compared to the conventional surface of the as-sintered ceramics, nano-sheet architecture promoted primary human osteoblast (HOB) adhesion as reflected by the activation of focal adhesion kinase (FAK) and expression of actin in HOBs. In summary, our study provided a simple solution based approach to endow HAp-TCP bioceramics with more favorable topographical features compared to the conventional ceramic surface.

Biodegradable Polymer‐Coated, Gelatin Hydrogel/Bioceramics Ternary Composites for Antitubercular Drug Delivery and Tissue Regeneration

A simple and effective strategy for the treatment of osteoarticular tuberculosis is proposed through combining tissue engineering approach with anti‐tuberculosis drug therapy. A series of tricalcium phosphate bioceramics (TPB) composites, coated by degradable polymer outside and loaded with rifampicin (RFP)‐containing gelatin hydrogel inside, were thus fabricated and successfully applied to deliver antitubercular drug RFP into osseous lesion and concomitantly to induce tissue regeneration. RFP‐loaded gelatin hydrogel/TPB composites could be readily prepared by filling RFP‐containing gelatin solution into TPB and then in situ crosslinking of gelatin with calcium ions. Depending on the concentrations of RFP, the loading efficiency of RFP in the composites varied in the range from approximately 2% to 5%. Moreover, the surface of these binary composites could be further coated by a biodegradable polymer, yielding biodegradable polymer‐coated, RFP‐containing gelatin hydrogel/TPB ternary composites. It was shown that in vitro release of RFP from the ternary composites could be effectively sustained for a long period of time. Besides, these composites revealed good biocompatibility towards the survival of MC‐3T3 cells in vitro and could be used for tissue regeneration in vivo in a rabbit model. The results indicate that TPB ternary composites have great potential for the treatment of osteoarticular tuberculosis.

Biocompatibility study of beta tricalcium phosphate bioceramics and chitosan biopolymer and their use as phantoms for medical imaging applications

AbstractBeta tricalcium phosphate (β‐TCP) bioceramics and chitosan biopolymers are used as biomedical implants because of their better biocompatibility and good bioresorption characteristics. As they are biomaterials, they have good interactions with microwave frequencies. β‐TCP and chitosan powder, films, pellets, and gel are prepared and studied at the S‐band microwave frequencies. Dielectric parameters such as dielectric constant, dielectric loss, conductivity, and S‐parameters are evaluated. Dielectric parameters of different forms of β‐TCP and chitosan show resemblance with that of human tissues. Hence, these materials can also be considered as potential phantoms for specific absorption rate measurements as well as in microwave imaging applications. © 2009 Wiley Periodicals, Inc. Microwave Opt Technol Lett 51: 2923–2927, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24752

Preparation and In Vitro Characterization of Wollastonite Doped Tricalcium Phosphate Bioceramics

In this work a new kind of CaSiO3-doped α-Ca3(PO4)2 ceramic materials, with compositions lying outside the field of the Ca3(PO4)2 solid solution in the system Ca3(PO4)2- CaSiO3, were obtained and some of their properties, relevant for bone repairing, were studied in vitro. Crystalline α-Ca3(PO4)2 solid solution and minor amounts of non-equilibrium residual glass were the only phases in the materials containing 2 and 5 wt% of CaSiO3. α-Ca3(PO4)2, crystalline eutectic-like phase and residual glass were observed for sample containing 15 and 20 wt% of CaSiO3. The mechanical strength improved for all the doped ceramics with regard to un-doped Ca3(PO4)2. The release of ionic Ca and Si in simulated physiological conditions increased with the content of CaSiO3 and favored α-Ca3(PO4)2 surface transformation. The soluble components extracted from the CaSiO3-doped α-Ca3(PO4)2 bioceramics were not cytotoxic to human fibroblastlike cells. Initial cell adhesion onto the surface of the materials seemed to be partially hindered by surface reactivity and remodeling, however those cells adhered to the experimental bioceramics were viable and proliferated normally.

Porous hydroxyapatite–tricalcium phosphate bioceramics

Porous bioceramics hydroxyapatite–tricalcium phosphate (HA–TCP), aimed to be applied in clinic, was fabricated by powder metallurgy and evaluated using both in vitro and in vivo models. Porous HA–TCP was supposed as a partially biodegradable material and designed as a scaffold for bone reconstruction or regeneration. The material processing was proposed and the physical properties as well as the microstructure feature were characterised here. Biological postulation of the relationship between seeding density, proliferation and viability of human osteoblasts cultured on the porous HA–TCP was quantitatively measured. Bone reconstruction was investigated both in vitro and in vivo by use of these biodegradable scaffolds with pore sizes ranged from 200 to 400 μm in diameter. The degradable bioceramic supported cellular proliferation seeded on the scaffold and showed normal differentiated function in vitro. Suitable pore size of the porous bioceramic was required if promotion of bone reconstruction was desired. Clinical trials showed that the bioceramics were successfully applied for bone reconstruction and regeneration and could be partially degraded in human body in 18 months. This approach suggests the feasibility of using porous HA–TCP bioceramics for the transplantation of autogenous osteoblasts to regenerate bone tissue.

MgO–Na2O–P2O5‐Based Sintering Additives for Tricalcium Phosphate Bioceramics

Effects of MgO–Na2O–P2O5‐based sintering additives on densification, microstructure, hardness, compression strength, and biodegradability of β‐tricalcium phosphate (β‐TCP) ceramics were studied. Three additive compositions were prepared and introduced into β‐TCP. Uniaxially compacted ceramic structures, sintered at 1250°C in air, were characterized. Scanning electron microscopy was used to study the microstructure. The X‐ray diffraction technique was used for phase analysis. Results showed that these additives modified the microstructure and improved the sintered density and mechanical properties. An increase of 9% in density, 40% in hardness and 38% in compression strength were achieved. Biodegradation analysis revealed that these additives could tailor the rate of resorption and hardness degradation of β‐TCP.

Oriented growth of surface grains in sintered β tricalcium phosphate bioceramics

Preferential orientation of sintered surface grains of beta tricalcium phosphate (β TCP) ceramic was studied by X-ray diffraction (XRD) method and scanning electron microcopy (SEM). The β TCP powder was prepared by calcining the precipitate at 800°C, obtained by precipitation method involving calcium nitrate and ammonium dihydrogen orthophosphate. The powder was compacted and sintered at 1150°C to ∼95% density. The surface grains of the above ceramic were found to preferentially orient with respect to a–b plane by XRD study. High grain growth was observed to the surface grains compared to the bulk grains.

Morphometric Evaluation of Tissue-Implant Reaction Associated With ALCAP and TCP Bioceramics In Vivo

The purpose of this investigation was to correlate the thickness of the fibrous capsule and the various histological components surrounding aluminum-calcium phosphate (ALCAP) and tricalcium phosphate (TCP) bioceramics at the subcutaneous (sc) and intraperitoneal (ip) implantation sites. The rational of conducting this investigation is to further elucidate the mechanisms of tissue-implant interaction. Thirteen Sprague-Dawley adult male albino rats were randomly divided into three groups. Animals in groups I and II (n = 5/group) were implanted at both ip and sc implantation sites with either ALCAP or TCP ceramics, respectively. Animals in group III (n

Phase Diagram of Wollastonite—Tricalcium Phosphate

A study of the system CaO·SiO2 (CS)‐3CaO·P2O5 (TCP) was conducted as a preliminary step toward obtaining polycrystalline wollastonite–tricalcium phosphate bioceramics. The results showed that the system is a true binary, with an invariant point at 1402 ± 3°C and a composition of 60 wt% CS/40 wt% TCP. These results are in disagreement with the reported data.