OBJECTIVE: Baghdadite (Ca3ZrSi2O9) cements of various composition have been investigated in this study regarding an application as endodontic filling materials.
METHODS: Cements were either obtained by mixing mechanically activated baghdadite powder with water (maBag) or by subsequently substituting the ß-tricalcium phosphate (ß-TCP) component in a brushite forming calcium phosphate cement. The cements were analyzed for their mechanical performance, injectability, radiopacity, phase composition and antimicrobial properties.
RESULTS: The cements demonstrated sufficient mechanical performance with a compressive strength of ∼1 MPa (maBag) and 2.3 - 17.4 MPa (substituted calcium phosphate cement), good injectability > 80 % depending on the powder to liquid ratio and an intrinsic radiopacity of 1.13 - 2.05 mm aluminum equivalent. Immersion in artificial saliva proved their bioactivity by the formation of calcium phosphate and calcium silicate precipitates on the cement surface. The bacterial activity of Staphylococcus aureus cultured on the surface of the cements was found to be similar compared to clinical standard ProRoot MTA cement or even reduced by a factor of 3 for Streptococcus mutans.
CONCLUSIONS: In combination with their antibacterial properties, baghdadite cements are thought to have the potential to fulfil the clinical requirements for endodontic filling materials.

Polymethyl methacrylate (PMMA) bone cement is commonly used in orthopedic surgeries to fill the bone defects or fix the prostheses. These cements are usually containing amounts of a nonbioactive radiopacifying agent such as barium sulfate and zirconium dioxide, which does not have a good interface compatibility with PMMA, and the clumps formed from these materials can scratch metal counterfaces. In this work, graphene oxide encapsulated baghdadite (GOBgh) nanoparticles were applied as radiopacifying and bioactive agent in a PMMA bone cement containing 2 wt.% of vancomycin (VAN). The addition of 20 wt.% of GOBgh (GOBgh20) nanoparticles to PMMA powder caused a 33.6% increase in compressive strength and a 70.9% increase in elastic modulus compared to the Simplex® P bone cement, and also enhanced the setting properties, radiopacity, antibacterial activity, and the apatite formation in simulated body fluid. In vitro cell assessments confirmed the increase in adhesion and proliferation of MG-63 cells as well as the osteogenic differentiation of human adipose-derived mesenchymal stem cells on the surface of PMMA-GOBgh20 cement. The chorioallantoic membrane assay revealed the excellent angiogenesis activity of nanocomposite cement samples. In vivo experiments on a rat model also demonstrated the mineralization and bone integration of PMMA-GOBgh20 cement within four weeks. Based on the promising results obtained, PMMA-GOBgh20 bone cement is suggested as an optimal sample for use in orthopedic surgeries.

Biological augmentation of bony defects in weight-bearing areas of both the acetabulum and the femur remains challenging. The calcium-silicate-based ceramic Baghdadite is a very interesting material to be used in the field of revision total hip arthroplasty for the treatment of bony defects in weight-bearing and non-weight-bearing areas alike. The aim of this study was to investigate the biocompatibility of Baghdadite utilizing an osteoblast-like, human osteosarcoma cell line (MG-63) and the human monocytic leukemia-derived cell line (THP-1). THP-1-derived macrophages and MG-63 were indirectly exposed to Baghdadite for 7 days using a transwell system. Viability was assessed with MTT assay and pH analysis. To investigate proliferation rate, both cell lines were labelled using CFSE and flow cytometrically analyzed. ELISA was used to measure the secretion of IL-1ß, IL-6 and TNFα. The investigation of viability, while showing a slight difference in optical density for the MTT assays in MG-63 cells, did not present a meaningful difference between groups for both cell lines. The comparison of pH and the proportion of living cells between groups did not present with a significant difference for both THP-1 and MG-63. Baghdadite did not have a relevant impact on the proliferation rate of the investigated cell lines. Mean fluorescence intensity was calculated between groups with no significant difference. Baghdadite exerted a proinflammatory effect, which could be seen in an upregulated production of TNFα in macrophages. Production of IL-1ß and IL-6 was not statistically significant, but the IL-6 ELISA showed a trend to an upregulated production as well. A similar effect on MG-63 was not observed. No relevant cytotoxicity of Baghdadite ceramics was encountered. Baghdadite ceramics exhibit a proinflammatory potential by significantly increasing the secretion of TNFα in THP-1-derived macrophages. Whether this proinflammatory potential results in a clinically relevant effect on osteointegration is unclear and requires further investigation. Baghdadite ceramics provide an interesting alternative to conventional bone substitutes and should be further investigated in a biomechanical and in vivo setting.

Bioceramic/polymer composites have dragged a lot of attention for treating hard tissue damage in recent years. In this study, we synthesized barium-doped baghdadite (Ba-BAG), as a novel bioceramic, and later developed fibrous composite poly (hydroxybutyrate) co (hydroxyvalerate)- polycaprolactone (PHBV-PCL) scaffolds containing different amounts of baghdadite (BAG) and Ba-BAG, intended to be used in bone regeneration. Our results demonstrated that BAG and Ba-doped BAG powders were synthesized successfully using the sol-gel method and their microstructural, physicochemical, and cytotoxical properties results were evaluated. In the following, PHBV/PCL composite scaffolds containing different amounts of BAG and Ba-BAG (1, 3, and 5 wt%) were produced by the wet electrospinning method. The porosity of scaffolds decreased from 78% to 72% in Ba-BAG-incorporated PHBV/PCL scaffolds. The compressive strength of the scaffolds was between 4.69 and 9.28 kPa, which was increased to their maximum values in the scaffolds with Ba-BAG. The presence of BAG and Ba-BAG in the polymer scaffolds resulted in increasing bioactivity, and it was introduced as a suitable way to control the degradation rate of scaffolds. The presence of the BAG component was a major reason for higher cell proliferation in reinforced PHBV/PCL polymeric scaffolds, while Ba existence played its influential role in the higher osteogenic activity of cells on Ba-BAG incorporated PHBV/PCL scaffolds. Thus, the incorporation of Ba-BAG bioceramic materials into the structure of polymeric PHBV/PCL scaffolds promoted their various properties, and allow these scaffolds to be used as promising candidates in bone tissue engineering applications.

This study investigated the relationship between the structure and mechanical properties of polycaprolactone (PCL) nanocomposites reinforced with baghdadite, a newly introduced bioactive agent. The baghdadite nanoparticles were synthesised using the sol-gel method and incorporated into PCL films using the solvent casting technique. The results showed that adding baghdadite to PCL improved the nanocomposites\' tensile strength and elastic modulus, consistent with the results obtained from the prediction models of mechanical properties. The tensile strength increased from 16 to 21 MPa, and the elastic modulus enhanced from 149 to 194 MPa with fillers compared to test specimens without fillers. The thermal properties of the nanocomposites were also improved, with the degradation temperature increasing from 388 °C to 402 °C when 10% baghdadite was added to PCL. Furthermore, it was found that the nanocomposites containing baghdadite showed an apatite-like layer on their surfaces when exposed to simulated body solution (SBF) for 28 days, especially in the film containing 20% nanoparticles (PB20), which exhibited higher apatite density. The addition of baghdadite nanoparticles into pure PCL also improved the viability of MG63 cells, increasing the viability percentage on day five from 103 in PCL to 136 in PB20. Additionally, PB20 showed a favourable degradation rate in PBS solution, increasing mass loss from 2.63 to 4.08 per cent over four weeks. Overall, this study provides valuable insights into the structure-property relationships of biodegradable-bioactive nanocomposites, particularly those reinforced with new bioactive agents.

Making composite scaffolds is one of the well-known methods to improve the properties of scaffolds used in bone tissue engineering. In this study, novel ceramic-based 3D porous composite scaffolds were successfully prepared using boron-doped hydroxyapatite, as the primary component, and baghdadite, as the secondary component. The effects of making composites on the properties of boron-doped hydroxyapatite-based scaffolds were investigated in terms of physicochemical, mechanical, and biological properties. The incorporation of baghdadite contributed to making more porous scaffolds (over 40%) with larger surface area and micropore volumes. The produced composite scaffolds almost solved the low degradation problem of boron-doped hydroxyapatite through the exhibition of higher biodegradation rates, which matched the degradation rate appropriate for the gradual transfer of loads from implants to newly formed bone tissues. Besides higher bioactivity, enhanced cell proliferation, as well as higher osteogenic differentiation (in scaffolds with baghdadite weight greater than 10%), were observed in composite scaffolds due to both physical and chemical modifications that occurred in composite scaffolds. Although our composite scaffolds were slightly weaker than boron-doped hydroxyapatite, their compressive strengths were higher than almost all composite scaffolds made by baghdadite incorporation in the literature. In fact, boron-doped hydroxyapatite provided a base for baghdadite to show mechanical strength suitable for cancellous bone defect treatments. Eventually, our novel composite scaffolds converged the advantages of both components to satisfy the various requirements needed for bone tissue engineering applications and take us one step forward on the road to fabricating an ideal scaffold.

Various artificial bone graft substitutes based on ceramics have been developed over the last 20 years. Among them, calcium-silicate-based ceramics, which are osteoconductive and can attach directly to biological organs, have received great attention for bone tissue engineering applications. However, the degradation rate of calcium-silicate and bone formation is often out of balance, resulting in stress shielding (osteopenia). A new strategy to improve the drawbacks of these ceramics is incorporating trace elements such as Zn, Mg, and Zr into their lattice structures, enhancing their physical and biological properties. Recently, baghdadite (Ca3ZrSi2O9) ceramic, one of the most appealing calcium-silicate-based ceramics, has demonstrated high bioactivity, biocompatibility, biodegradability, and cell interaction. Because of its physical, mechanical, and biological properties and ability to be shaped using various fabrication techniques, baghdadite has found high potential in various biomedical applications such as coatings, fillers, cement, scaffolds, and drug delivery systems. Undoubtedly, there is a high potential for this newly developed ceramic to contribute significantly to therapies to provide a tremendous clinical outcome. This review paper aims to summarize and discuss the most relevant studies performed on baghdadite-based ceramics and composites by focusing on their behavior in vivo and in vitro.

This work studies the mechanical and biological properties of Baghdadite (BAG, Ca3ZrSi2O9) coating manufactured on Ti6Al4V substrates by hybrid water-stabilized plasma spray (WSP-H). Hydroxyapatite (HAp, Ca10(PO4)6(OH)2) coating was produced by gas-stabilized atmospheric plasma spray and used as a reference material. Upon spraying, the BAG coating exhibited lower crystallinity than the HAp coating. Mechanical testing demonstrated superior properties of the BAG coating: its higher hardness, elastic modulus as well as a better resistance to scratch and wear. In the cell viability study, the BAG coating presented better human osteoblast attachment and proliferation on the coating surface after three days and seven days compared to the HAp counterpart. Furthermore, the gene expression study of human osteoblasts indicated that the BAG coating surface showed higher expression levels of osteogenic genes than those on the HAp coating. Overall, this study indicates that enhanced mechanical and bioactive properties can be achieved for the BAG coating compared to the benchmark HAp coating. It is therefore concluded here that the BAG coating is a potential candidate for coating orthopedic implants.

Porous Si-based ceramic scaffolds are widely attracted in biomedical tissue engineering application. Despite the attractive properties of these materials, their weak mechanical properties and high degradability in vitro and in vivo environment can limit their application as biomedical devises. Applying a thin layer of polymer on the surface of porous scaffolds can improve the mechanical properties and control the degradation rate. In this study, we produced new modified scaffolds with polymers coating in order to improved mechanical and biological properties of Si-based ceramics scaffolds. The results showed that applying 6 wt% PCLF polymer on the surface of Bagh-15 wt%Dio scaffolds delayed apatite formation compared to unmodified scaffolds. On the other hand, in the modified scaffolds, apatite formation was observed. The degradation rate of unmodified scaffolds was decreased around 82% after 28 days soaking in PBS solution. Based on the MTT assay and SEM micrographs, the BMS cells were spread and attached well on the surface of the scaffolds, which indicated a good biocompatibility. The results showed that these scaffolds have the potential to be used as a temporary substrate for bone tissue engineering application.

Brushite cements have been clinically used for irregular bone defect filling applications, and various strategies have been previously reported to modify and improve their physicochemical properties such as strength and injectability. However, strategies to address other limitations of brushite cements such as low radiopacity or acidity without negatively impacting mechanical strength have not yet been reported. In this study, we report the effect of substituting the beta-tricalcium phosphate reactant in brushite cement with baghdadite (Ca3ZrSi2O9), a bioactive zirconium-doped calcium silicate ceramic, at various concentrations (0, 5, 10, 20, 30, 50, and 100 wt%) on the properties of the final brushite cement product. X-ray diffraction profiles indicate the dissolution of baghdadite during the cement reaction, without affecting the crystal structure of the precipitated brushite. EDX analysis shows that calcium is homogeneously distributed within the cement matrix, while zirconium and silicon form cluster-like aggregates with sizes ranging from few microns to more than 50 µm. X-ray images and µ-CT analysis indicate enhanced radiopacity with increased incorporation of baghdadite into brushite cement, with nearly a doubling of the aluminium equivalent thickness at 50 wt% baghdadite substitution. At the same time, compressive strength of brushite cement increased from 12.9 ± 3.1 MPa to 21.1 ± 4.1 MPa with 10 wt% baghdadite substitution. Culture medium conditioned with powdered brushite cement approached closer to physiological pH values when the cement is incorporated with increasing amounts of baghdadite (pH = 6.47 for pure brushite, pH = 7.02 for brushite with 20 wt% baghdadite substitution). Baghdadite substitution also influenced the ionic content in the culture medium, and subsequently affected the proliferative activity of primary human osteoblasts in vitro. This study indicates that baghdadite is a beneficial additive to enhance the radiopacity, mechanical performance and cytocompatibility of brushite cements.