Tricalcium Phosphate Ceramics Research Articles

Characterization of Porous β-Type Tricalcium Phosphate Ceramics Formed via Physical Foaming with Freeze-Drying.

Porous β-tricalcium phosphate (Ca3(PO4)2; β-TCP) was prepared via freeze-drying and the effects of this process on pore shapes and sizes were investigated. Various samples were prepared by freezing β-TCP slurries above a liquid nitrogen surface at -180 °C with subsequent immersion in liquid nitrogen at -196 °C. These materials were then dried under reduced pressure in a freeze-dryer, after which they were sintered with heating. Compared with conventional heat-based drying, the resulting pores were more spherical, which increased both the mechanical strength and porosity of the β-TCP. These materials had a wide range of pore sizes from 50 to 200 µm, with the mean and median values both approximately 100 µm regardless of the freeze-drying conditions. Mercury porosimetry data showed that the samples contained small, interconnected pores with sizes of 1.24 ± 0.25 µm and macroscopic, interconnected pores of 25.8 ± 4.7 µm in size. The effects of nonionic surfactants having different hydrophilic/lipophilic balance (HLB) values on foaming and pore size were also investigated. Materials made with surfactants having lower HLB values exhibited smaller pores and lower porosity, whereas higher HLB surfactants gave higher porosity and slightly larger macropores. Even so, the pore diameter could not be readily controlled solely by adjusting the HLB value. The findings of this work indicated that high porosity (>75%) and good compressive strength (>2 MPa) can both be obtained in the same porous material and that foaming agents with HLB values between 12.0 and 13.5 were optimal.

Antimicrobial and Cell-Friendly Properties of Cobalt and Nickel-Doped Tricalcium Phosphate Ceramics.

β-Tricalcium phosphate (β-TCP) is widely used as bone implant material. It has been observed that doping the β-TCP structure with certain cations can help in combating bacteria and pathogenic microorganisms. Previous literature investigations have focused on tricalcium phosphate structures with silver, copper, zinc, and iron cations. However, there are limited studies available on the biological properties of β-TCP containing nickel and cobalt ions. In this work, Ca10.5-xNix(PO4)7 and Ca10.5-xCox(PO4)7 solid solutions with the β-Ca3(PO4)2 structure were synthesized by a high-temperature solid-state reaction. Structural studies revealed the β-TCP structure becomes saturated at 9.5 mol/% for Co2+ or Ni2+ ions. Beyond this saturation point, Ni2+ and Co2+ ions form impurity phases after complete occupying of the octahedral M5 site. The incorporation of these ions into the β-TCP crystal structure delays the phase transition to the α-TCP phase and stabilizes the structure as the temperature increases. Biocompatibility tests conducted on adipose tissue-derived mesenchymal stem cells (aMSC) using the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay showed that all prepared samples did not exhibit cytotoxic effects. Furthermore, there was no inhibition of cell differentiation into the osteogenic lineage. Antibacterial properties were studied on the C. albicans fungus and on E. coli, E. faecalis, S. aureus, and P. aeruginosa bacteria strains. The Ni- and Co-doped β-TCP series exhibited varying degrees of bacterial growth inhibition depending on the doping ion concentration and the specific bacteria strain or fungus. The combination of antibacterial activity and cell-friendly properties makes these phosphates promising candidates for anti-infection bone substitute materials.

Study of Tricalcium Phosphate Ceramics Doped with Gadolinium Ions with Various EPR Techniques

Tricalcium phosphate (TCP)-based materials, such as β-Ca3(PO4)2 doped with rare earth ions (RE), have shown applications as biomaterials, lighting emitting materials, scintillating materials, in vivo imaging probes, and thermoluminescent dosimeters. Their properties are found to be dependent on the distribution of RE3+ on Ca2+ sites that can be controlled by pulsed electron paramagnetic resonance (EPR) and electron spin echo envelop modulation (ESEEM) experiments. The main spectroscopic parameters (spin Hamiltonian values) of Gd3+ and nitrogen impurity centers are quantitatively determined (g-factor, the fine structure parameters D and E, the hyperfine constants A) as well as dynamic characteristics: spin–lattice T1 and spin–spin T2 relaxation times. Based on the analysis of the EPR datasets, the interatomic distance between Gd3+ and 31P was estimated in the dipole–dipole approximation. Two structurally nonequivalent Gd3+ positions in the β-TCP structure have been identified. The obtained valuable results demonstrate applicability of modern EPR techniques to characterize Gd-TCP systems despite the powder structure of the material and high electron spin S = 7/2 of Gd3+ ions.

Calcium-phosphate ceramics in spine surgery: features of regeneration and use

The review is based on the analysis of 53 literature sources from PubMed, Google, Google Scholar, and Cochrane Library. Among the substitutes for autogenous bone grafts in spine surgery, ceramic biomaterials are the largest studied group, among which certain niche is occupied by calcium phosphate ceramics (CPCs). Hydroxylapatite, tricalcium phosphate and biphasic ceramics with all parts of hydroxylapatite and tricalcium phosphate are widely used in spine surgery. The advantage of using CPCs is their biocompatibility, osteoconductivity, osteoinductivity, osteoimmunomodulation and the ability to stimulate angiogenesis — the main components that ensure bone regeneration. In the given review, the peculiarities of regeneration in the interface “ceramic material — bone tissue” depending on the composition, surface structure, and crystallinity of the material are noted. The positive results of the experimental studies led to the use of CPCs in the clinic. CPCs with autogenous bone grafts are successfully used in posterior and posterolateral lumbar spondylodesis, which allows reducing significantly the volume of autologous bone. A new direction is the development of non-metallic combined cages, which are used to perform anterior cervical discectomy and spondylodesis. The composition of these cages includes various polymers in combination with CPCs and bone autogenous graft to ensure high-quality spondylodesis, reduce of stress-shielding and subsidence of the cage. A special approach requires the study of degradation and resorption by osteoclasts of various CPCs in order to control and synchronize the process of “resorption — bone formation”. Among the issues for the further research, the molecular mechanisms of osteoimunomodulation and factors that stimulate osseointegration and osteoinduction in the management of reparative osteogenesis should be further explored.

Influence of Synthesis Conditions on Gadolinium-Substituted Tricalcium Phosphate Ceramics and Its Physicochemical, Biological, and Antibacterial Properties.

Gadolinium-containing calcium phosphates are promising contrast agents for various bioimaging modalities. Gadolinium-substituted tricalcium phosphate (TCP) powders with 0.51 wt% of gadolinium (0.01Gd-TCP) and 5.06 wt% of (0.1Gd-TCP) were synthesized by two methods: precipitation from aqueous solutions of salts (1) (Gd-TCP-pc) and mechano-chemical activation (2) (Gd-TCP-ma). The phase composition of the product depends on the synthesis method. The product of synthesis (1) was composed of β-TCP (main phase, 96%), apatite/chlorapatite (2%), and calcium pyrophosphate (2%), after heat treatment at 900 °C. The product of synthesis (2) was represented by β-TCP (main phase, 73%), apatite/chlorapatite (20%), and calcium pyrophosphate (7%), after heat treatment at 900 °C. The substitution of Ca2+ ions by Gd3+ in both β-TCP (main phase) and apatite (admixture) phases was proved by the electron paramagnetic resonance technique. The thermal stability and specific surface area of the Gd-TCP powders synthesized by two methods were significantly different. The method of synthesis also influenced the size and morphology of the prepared Gd-TCP powders. In the case of synthesis route (1), powders with particle sizes of tens of nanometers were obtained, while in the case of synthesis (2), the particle size was hundreds of nanometers, as revealed by transmission electron microscopy. The Gd-TCP ceramics microstructure investigated by scanning electron microscopy was different depending on the synthesis route. In the case of (1), ceramics with grains of 1–50 μm, pore sizes of 1–10 µm, and a bending strength of about 30 MPa were obtained; in the case of (2), the ceramics grain size was 0.4–1.4 μm, the pore size was 2 µm, and a bending strength of about 39 MPa was prepared. The antimicrobial activity of powders was tested for four bacteria (S. aureus, E. coli, S. typhimurium, and E. faecalis) and one fungus (C. albicans), and there was roughly 30% of inhibition of the micro-organism’s growth. The metabolic activity of the NCTC L929 cell and viability of the human dental pulp stem cell study demonstrated the absence of toxic effects for all the prepared ceramic materials doped with Gd ions, with no difference for the synthesis route.

Barium-Substituted Tricalcium Phosphate Ceramics

Barium-Substituted Tricalcium Phosphate Ceramics

Construction of a drug-containing microenvironment for in situ bone regeneration

Bioactive glass-coated hierarchical porous tricalcium phosphate ceramics were constructed as both bone scaffolds and drug delivery devices to treat S. aureus-infected bone defects.

Antibacterial and cell-friendly copper-substituted tricalcium phosphate ceramics for biomedical implant applications

The development of new materials with antibacterial properties and the scope to decrease or eliminate the excessive antibiotic use is an urgent priority due to the growing antibiotic resistance-related mortalities. New bone substitute materials with intrinsic antibacterial characteristics are highly requested for various clinical applications. In this study, the choice of copper ions as substitutes for calcium in tricalcium phosphate (TCP) has been justified by their pronounced broad-spectrum antibacterial properties. Copper-substituted TCP (Cu-TCP) ceramics with the copper content of 1.4 and 0.1 wt% were synthesized by mechano-chemical activation. X-ray diffraction (XRD) analyses established that both pure and copper-containing compounds adopted the structure of whitlockite (β-TCP). XRD and electron paramagnetic resonance (EPR) spectroscopy revealed the partial isovalent substitution of calcium ions with copper ions in the β-TCP lattice. With the use of infrared and EPR spectroscopies, it was detected that carbonate ions got incorporated into the β-TCP structure during the synthesis procedure. By releasing the tension in the M(5)O6 octahedron consequential to the lower CaO bond length than the corresponding sum of ionic radii, the substitution of calcium with smaller copper ions stabilizes the structure of β-TCP. As concluded form the thermal analyses, the introduction of Cu prevented the polymorphic transformation of β- to α-TCP. At the same time, the introduction of Cu to the β-TCP structure enhanced the crystal growth and porosity of the ceramics, which had a positive effect on the cytocompatibility of the material. The MTT colorimetric assay showed that the metabolic activity of the mouse fibroblast NCTC L929 cell line during 24 h of incubation with 3-day extracts from Cu-TCP (1.4 wt%) and β-TCP pellets in the cell culture medium was similar to the negative control, indicating the absence of any inhibitory effects on cells. The seeding and the growth of human dental pulp stem cells on the surface of Cu-TCP (1.4 wt%) and β-TCP ceramics also showed the absence of any signs of cytotoxicity. Finally, microbiological assays demonstrated the antibacterial activity of Cu-TCP ceramics against Escherichia coli and Salmonella enteritidis, whereas β-TCP did not exhibit such an activity. Overall, the addition of Cu ions to β-TCP improves its antibacterial properties without diminishing the biocompatibility of the material, thus making it more attractive than pure β-TCP for clinical applications such as synthetic bone grafts and orthopaedic implant coatings.

Controlled release of soy isoflavones from multifunctional 3D printed bone tissue engineering scaffolds

Recent challenges in post-surgical bone tumor management have elucidated the need for a multifunctional scaffold, which can be used for residual tumor-cell suppression, defect repair, and simultaneous bone regeneration. In this perspective, 3D printing allows to create a wide variety of patient-specific implant with complex porous architecture and compatible mechanical strength to that of cancellous bone. Here, a multifunctional bone graft substitute is designed by incorporating the three primary soy isoflavones: genistein, daidzein, and glycitein onto a 3D printed (3DP) tricalcium phosphate (TCP) scaffolds with designed pores, endowing them with in vitro chemopreventive, bone-cell proliferating and immune-modulatory potential. The interconnected porosity and biodegradability of 3DP TCP ceramics have allowed controlled release kinetics of genistein, daidzein and glycitein in acidic and physiological buffer medium for 16 days, which is fitted with Korsmeyer-Peppas model. Presence of genistein, a well-known natural biomolecule shows a 90% reduction in vitro osteosarcoma (MG-63) cell viability and proliferation after 11 days. Meanwhile, daidzein, the other primary isoflavone, promotes in vitro cellular attachment and enhances viability and proliferation of human fetal osteoblast cell (hFOB). Furthermore, controlled release of genistein, daidzein, and glycitein from 3DP TCP scaffold demonstrates improved hFOB cell proliferation, viability, and differentiation in a dynamic flow-perfusion bioreactor, which is utilized to better simulate the clinical microenvironment. Finally, in vivo H&E staining confirms controlled co-delivery of genistein-daidzein-glycitein from 3DP scaffold carefully modulated neutrophil recruitment to the surgery site after 24 h of implantation in a rat distal femur model. These results advance our understanding towards multipronged therapeutic approaches utilizing synthetic bone graft substitutes as a drug delivery vehicle, and more importantly, demonstrate the feasibility of localized tumor cell suppression and bone cell proliferation for post-surgical defect repair application. Statement of SignificanceDesigned multimodal porosity of 3D printed TCP scaffold allows a controlled and sustained release of soy isoflavones, genistein, daidzein and glycitein in both physiological and acidic pH. Presence of genistein shows 90% reduction in vitro bone cancer cell viability and proliferation. Meanwhile, controlled release of genistein, daidzein, and glycitein from 3DP TCP scaffolds demonstrate improved osteoblast cell proliferation, viability, and differentiation in static and dynamic flow-perfusion bioreactor. Furthermore, H&E staining at 24 h post-surgical specimens from rat distal femur model shows neutrophil recruitment at the surgery site is significantly decreased, suggesting the anti-inflammatory property of soy isoflavones. This work provides deeper understanding on the design of a multifunctional 3D printed patient-specific scaffold with enhanced in vitro chemopreventive, osteogenic and in vivo anti-inflammatory ability.

Metallic ion doped tri-calcium phosphate ceramics: Effect of dynamic loading on in vivo bone regeneration

The present study was carried out to evaluate the effect of dynamic loading on bone regeneration performance of different doped β-tri-calcium phosphate ceramics. We have developed porous beta tri-calcium phosphate (β-TCP), 5%zinc doped, 5% magnesium doped and 5% titanium doped β-TCP by aqueous solution combustion technique. All the synthesized β-TCP powders showed pore size of 21–146 μm (pure β-TCP), 16–142 μm (Zn-β-TCP), 28–156 μm (Mg- β-TCP) and 14–173 μm (Ti-β-TCP) while their apparent porosity 17.89%, 28.09%, 26.54% and 25.87% respectively. The pure and doped samples were implanted in femoral bone defect model (rabbit) to assess bone regeneration under dynamic loading. Bone regeneration was assessed after 1 and 2 month post-implantation on the basis of clinical radiological, histological, fluorochrome labelling, micro computed tomography (μ-CT) and scanning electron microscopy (SEM). Radiological and fluorochrome labelling study showed reduced size of 5%Ti-β-TCPimplant vis-à-vis more new bone formation as compared to other groups. Micro-CT of the implanted bone sample showed a significant amount of newly formed bony tissue surrounding the Ti-β-TCP implant as compared to other samples. Similar findings of less interfacial gap between the implant and bone were also observed in SEM study. However, all the doped materials are suitable as bone grafting material and have potential for application in bone tissue engineering.

Synthesis and characterization of strontium and chlorine co-doped tricalcium phosphate

The strontium (Sr2+) and chlorine (Cl−) substituted tricalcium phosphate (TCP) were synthesized via aqueous precipitation method. To understand the effect of the Sr2+ and Cl− doping on mechanical properties of tricalcium phosphate (TCP) ceramics, dense TCP compacts of different compositions were prepared and sintered at 1100 °C for 1 h. X-ray diffraction of sintered samples revealed that dopants turn into β-TCP to HA phase transformation during sintering. The binary combination and amount of co-dopants significantly affect the microstructure. The microhardness of the samples increased with increasing of the Sr2+ and Cl− ion concentrations. Cl− ion addition, 2.5–10 mol% affect micro hardness results negatively. A comparison between samples were carried out and differences were considered statistically significant at p < 0.05 (standard deviation: 1.2296 GPa).

Management of Collapse Tibial Plateau Fractures Using a Hydroxyapatite-Tricalcium Phosphate Ceramic(ATLANTIK�) and Plate Osteosynthesis

The treatment of bone defects in complex proximal tibial plateau fractures is a challenging situation and biphasic tricalcium phosphate (BCP) ceramics are considered the most promising alternative to autologous bone graft. The aim of the experimental part was to retrospectively asses the use of Atlantik� BCP (a mixture of 70% Hydroxyapatite and 30% beta-tricalcium phosphate) combined with plate osteosynthesis for management of 27 collapse tibial plateau fractures. All fractures healed after a mean time 2.8 months, while the mean time for disappearance the radiolucent zones between the implanted ceramic and receiving tissue was 15 weeks. We noticed a Neer score of 85 points with no reaction to bone substitute or evidence of biomaterial degradation. The study demonstrated that biphasic ceramic biomaterial Atlantik�, combined with supportive plate osteosynthesis, is an effective synthetic bone substitute due to a fast healing and good quality osseointegration.

APPLICATION OF BIOCERAMICS IN THE TREATMENT OF POST-TRAUMATIC PERIODONTITIES OF PERMANENT TEETH IN CHILDREN

Relevance. In children, post-traumatic complications in the teeth with incomplete formation of the root often lead to stopping the development of the root and premature loss of teeth. The instability of the results of endodontic treatment with calcium hydroxide preparations leads to the search for new treatments. Materials based on tricalcium phosphate ceramics attract attention because they contribute to the regeneration of bone tissue. Objective: to evaluate the effectiveness of endodontic treatment of post-traumatic periodontitis of permanent teeth with incomplete root formation using bioceramics based on biological hydroxyapatite "Osteopatite ceramic" brand "OK 015". Materials and methods. In children aged 9-15 years, 17 permanent teeth with post-traumatic complications were treated. In 12 cases, this was chronic granulating periodontitis. For a prolonged temporary obturation of root canals, a paste was used, which was prepared by mixing metronidazole and "OK 015" granules. The treatment was monitored every other day, 2 weeks, 1, 3, 6, 9, 12 months. Permanent root canal filling was performed after apexification. Results. In the early stages of the observation of complications of treatment was not observed. 3 months after treatment, bone structure regeneration was activated, in 1 tooth – apexification. After 6 months, the positive dynamics of bone regeneration was observed in 100 % of children. X-ray reconstruction of bone tissue was confirmed in 35,3 % of cases, apexification occurred in 41,2 %. After 9 months, bone resection was observed in 59 % of cases, apexification – in 64 % of the teeth. After 12 months, bone tissue recovery occurred in 76,5 % of cases, in 94 % – apexification. Thus, the rate of apexification is ahead of the processes of reparative osteogenesis. The formation of a mineralized barrier is not always accompanied by a complete restoration of the structure of the periapical bone. Conclusion. Material based on biological hydroxyapatite "Osteoapatite ceramic" brand "OK 015" for temporary obturation of the root canal promotes apexification and regeneration of bone tissue in the periapical region in the process of endodontic treatment of permanent teeth with unformed root in children.

Modulating Bone Regeneration in Rabbit Condyle Defects with Three Surface-Structured Tricalcium Phosphate Ceramics.

Tricalcium phosphate (TCP) ceramics are used as bone void fillers because of their bioactivity and resorbability, while their performance in bone regeneration and material resorption vary with their physical properties (e.g., the dimension of the crystal grain). Herein, three TCP ceramic bone substitutes (TCP-S, TCP-M, and TCP-L) with gradient crystal grain size (0.77 ± 0.21 μm for TCP-S, 1.21 ± 0.35 μm for TCP-M and 4.87 ± 1.90 μm for TCP-L), were evaluated in a well-established rabbit lateral condylar defect model (validated with sham) with respect to bone formation and material resorption up to 26 weeks. Surface structure-dependent bone regeneration was clearly shown after 4 weeks implantation with TCP-S having most mineralized bone (20.2 ± 3.4%), followed by TCP-M (14.0 ± 3.5%), sham (8.1 ± 4.2%), and TCP-L (6.6 ± 2.6%). Afterward, the amount of mineralized bone was similar in all the three groups, but bone marrow and material resorption varied. After 26 weeks, TCP-S induced most bone tissue formation (mineralized bone + bone marrow) (61.6 ± 7.8%) and underwent most material resorption (80.1 ± 9.0%), followed by TCP-M (42.9 ± 5.2% and 61.4 ± 8.0% respectively), TCP-L (28.3 ± 5.5% and 45.6 ± 9.7% respectively), and sham (25.7 ± 4.2%). Given the fact that the three ceramics are chemically identical, the results indicate that the surface structure (especially, the crystal grain size) of TCP ceramics can greatly tune their bone regeneration potential and the material resorption in rabbit condyle defect model, with the submicron surface structured TCP ceramic performing the best.

Current Concepts in Scaffolding for Bone Tissue Engineering.

Bone disorders are of significant worry due to their increased prevalence in the median age. Scaffold-based bone tissue engineering holds great promise for the future of osseous defects therapies. Porous composite materials and functional coatings for metallic implants have been introduced in next generation of orthopedic medicine for tissue engineering. While osteoconductive materials such as hydroxyapatite and tricalcium phosphate ceramics as well as some biodegradable polymers are suggested, much interest has recently focused on the use of osteoinductive materials like demineralized bone matrix or bone derivatives. However, physiochemical modifications in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, mineralization and osteogenic differentiation are required. This paper reviews studies on bone tissue engineering from the biomaterial point of view in scaffolding. Level of evidence: I.

Early clinical and radiographic outcomes of trabecular metal total ankle using transfibular approach

Musculoskeletal conditions are the most commonly occurring medical conditions, and they have a considerable influence on the quality of health and living standard of the millions of people across the world. Annually, around the globe, approximately 2.3 million bone-tissue graft transplants are performed. The bone fracture, osteoporosis, osteoarthritis, and various neoplastic disorders are the common clinical problems related with bone and skeletal system. The common approaches to these bone problems are autografts or allografts. These protocols have certain limitations such as resorption, donor site morbidity, compromised supply, rejection rate up to 50% at some sites, and the risk of inducing transmissible diseases. Consequently, considerable attention has been directed toward the use of bioactive materials as synthetic grafts for bone regeneration. These include hydroxyapatite (HAP), tricalcium phosphate, bioactive glass, and glass ceramics. More significantly, calcium phosphates are the major constituent of bone mineral. The most extensively used synthetic calcium phosphate ceramic for bone replacement is HAP with a chemical formula of Ca10(PO4)6(OH)2. It has Ca:P molar ratio of 1.667 and is regarded as the most stable composition compared to other calcium phosphate ceramic within a pH range of 4.2–8.0. Calcium phosphate cement is one of the most important types of bioceramic material. In combination with various calcium phosphates, an injectable paste can be formed, which is cured over a period of time, in which resultant product is a carbonate apatite. The cements cure in situ and are gradually resorbed and replaced by a newly formed bone. The concept of a bioactive glass was pioneered by Hench and colleagues. The composition of Bioglass is a series of special designed glasses, consisting of a Na2O–CaO–SiO2 glass with the addition of P2O5, B2O3, and CaF2. A biologically active hydroxycarbonate apatite layer is formed on the surface of bioactive glasses in vitro and in vivo. The chemical properties could be controlled in bioactive glasses and eventually its bonding to tissue. Certain specialized compositions of Bioglass (e.g., 45S5) can bond to soft tissue as well as bone, in either bulk or particulate form. Moreover, apatite-wollastonite glass-ceramic, with an assembly of small apatite particles effectively reinforced by β-wollastonite exhibit not only bioactivity, but also a fairly high mechanical strength. Mechanical properties like the bending strength, toughness against fracture, and Young’s modulus of A-W glass-ceramic are the highest among bioactive glasses and glass-ceramics enabling it to be used in some compression load-bearing applications. Overall, the advantages of bioactive glasses are the magnitude of their surface reactivity and the ability to change the chemical composition, thus facilitating bonding with variety of tissues. Mechanical properties are the drawback as these materials have relatively low bending strength in comparison to other ceramic materials. The bioactive calcium phosphate ceramics, bioglasses, and glass-ceramics form a mechanically strong interfacial bond with bone. The strength of the bond is normally equivalent to or greater than the strength of the host bone, depending on test conditions. Therefore, all of these materials have excellent bioactivity. Nevertheless, bioactive ceramics have a flexural strength, strain-to-failure, and fracture toughness, which is less than the bone and the elastic modulus is greater than the bone. In other words, most bioactive materials have a less-than-optimal biomechanical compatibility when used in load-bearing applications. An approach to mitigate this problem involves designing and structural tailoring of bioactive composites. The concept of matching the mechanical behavior of an implant, with the tissue to be replaced in order to solve the problem of stress shielding of conventional biomaterials, was proposed by Bonfield et al. Thus, the composite approach can significantly meet the challenge of a long life, as a demand for the new-generation implant materials. Calcium phosphate ceramics, bioglasses, and glass ceramics are generally considered to be bone bioactive ceramics. These materials generally get bonded to the surrounding osseous tissue and enhance further bone-tissue formation. The direct bone bonding to bioactive glasses was first observed and reported by Hench et al., since then considerable progress has been made in understanding the basic mechanism of the formation of bone and biomaterial bond and its effect on bone formation.

Bone Morphogenetic Protein-7 Enhances Degradation of Osteoinductive Bioceramic Implants in an Ectopic Model.

Background:The aim of the present study was to evaluate the degradation pattern of highly porous bioceramics as well as the bone formation in presence of bone morphogenetic protein 7 (BMP-7) in an ectopic site.Methods:Novel calcium phosphate ceramic cylinders sintered at 1,300°C with a total porosity of 92–94 vol%, 45 pores per inch, and sized 15 mm (Ø) × 5 mm were grafted on the musculus latissimus dorsi bilaterally in 10 Göttingen minipigs: group I (n = 5): hydroxyapatite (HA) versus biphasic calcium phosphate (BCP), a mixture of HA and tricalcium phosphate (TCP) in a ratio of 60/40 wt%; group II (n = 5): TCP versus BCP. A test side was supplied in situ with 250 μg BMP-7. Fluorochrome bone labeling and computed tomography were performed in vivo. Specimens were evaluated 14 weeks after surgery by environmental scanning electron microscopy, fluorescence microscopy, tartrate-resistant acid phosphatase, and pentachrome staining.Results:Bone formation was enhanced in the presence of BMP-7 in all ceramics (P = 0.001). Small spots of newly formed bone were observed in all implants in the absence of BMP-7. Degradation of HA and BCP was enhanced in the presence of BMP-7 (P = 0.001). In those ceramics, osteoclasts were observed. TCP ceramics were almost completely degraded independently of the effect of BMP-7 after 14 weeks (P = 0.76), osteoclasts were not observed.Conclusions:BMP-7 enhanced bone formation and degradation of HA and BCP ceramics via osteoclast resorption. TCP degraded via dissolution. All ceramics were osteoinductive. Novel degradable HA and BCP ceramics in the presence of BMP-7 are promising bone substitutes in the growing individual.

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.

Clinical Application of Ceramics in Anterior Cervical Discectomy and Fusion: A Review and Update.

Study Design:Narrative review.Objectives:Anterior cervical discectomy and fusion (ACDF) is a reliable procedure, commonly used for cervical degenerative disc disease. For interbody fusions, autograft was the gold standard for decades; however, limited availability and donor site morbidities have led to a constant search for new materials. Clinically, it has been shown that calcium phosphate ceramics, including hydroxyapatite (HA) and tricalcium phosphate (TCP), are effective as osteoconductive materials and bone grafts. In this review, we present the current findings regarding the use of ceramics in ACDF.Methods:A review of the relevant literature examining the clinical use of ceramics in anterior cervical discectomy and fusion procedures was conducted using PubMed, OVID and Cochrane.Result:HA, coralline HA, sandwiched HA, TCP, and biphasic calcium phosphate ceramics were used in combination with osteoinductive materials such as bone marrow aspirate and various cages composed of poly-ether-ether-ketone (PEEK), fiber carbon, and titanium. Stand-alone ceramic spacers have been associated with fracture and cracks. Metallic cages such as titanium endure the risk of subsidence and migration. PEEK cages in combination with ceramics were shown to be a suitable substitute for autograft.Conclusion:None of the discussed options has demonstrated clear superiority over others, although direct comparisons are often difficult due to discrepancies in data collection and study methodologies. Future randomized clinical trials are warranted before definitive conclusions can be drawn.

Cells responding to surface structure of calcium phosphate ceramics for bone regeneration.

Surface structure largely affects the inductive bone-forming potential of calcium phosphate (CaP) ceramics in ectopic sites and bone regeneration in critical-sized bone defects. Surface-dependent osteogenic differentiation of bone marrow stromal cells (BMSCs) partially explained the improved bone-forming ability of submicron surface structured CaP ceramics. In this study, we investigated the possible influence of surface structure on different bone-related cells, which may potentially participate in the process of improved bone formation in CaP ceramics. Besides BMSCs, the response of human brain vascular pericytes (HBVP), C2C12 (osteogenic inducible cells), MC3T3-E1 (osteogenic precursors), SV-HFO (pre-osteoblasts), MG63 (osteoblasts) and SAOS-2 (mature osteoblasts) to the surface structure was evaluated in terms of cell proliferation, osteogenic differentiation and gene expression. The cells were cultured on tricalcium phosphate (TCP) ceramics with either micron-scaled surface structure (TCP-B) or submicron-scaled surface structure (TCP-S) for up to 14 days, followed by DNA, alkaline phosphatase (ALP) and quantitative polymerase chain reaction gene assays. HBVP were not sensitive to surface structure with respect to cell proliferation and osteogenic differentiation, but had downregulated angiogenesis-related gene expression (i.e. vascular endothelial growth factor) on TCP-S. Without additional osteogenic inducing factors, submicron-scaled surface structure enhanced ALP activity and osteocalcin gene expression of human (h)BMSCs and C2C12 cells, favoured the proliferation of MC3T3-E1, MG63 and SAOS-2, and increased ALP activity of MC3T3-E1 and SV-HFO. The results herein indicate that cells with osteogenic potency (either osteogenic inducible cells or osteogenic cells) could be sensitive to surface structure and responded to osteoinductive submicron-structured CaP ceramics in cell proliferation, ALP production or osteogenic gene expression, which favour bone regeneration. Copyright © 2017 John Wiley & Sons, Ltd.