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.

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.

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.

Bone repair has been a new approach in regenerative medicine especially by application of stem cells. Discovering a suitable combination of scaffolds to stimulate osteogenesis is one of the major concerns in this issue. Porous polymeric scaffolds such as poly l-lactic acid (PLLA) have been attracted a lot of attention because of their biodegradability. In the present study, we have been coated Baghdadite on the plasma-treated surface of PLLA and evaluated osteogenic potential of mesenchymal stem cells (MSCs). Adipose tissue-derived mesenchymal stem cells (AD-MSCs) were cultured on PLLA and PLLA-Baghdadite scaffolds, and cell properties were characterized by MTT assay, scanning electron microscope, and FTIR analysis. Then, osteogenic differentiation potential of AD-MSCs has been investigated, such as alkaline phosphatase (ALP) activity, calcium mineral deposition, and the expression of bone-related genes (RUNX2, ALP, and OCN). The results have been indicated that calcium content and ALP activity of cells cultured on PLLA-Baghdadite nanofibers were higher than that of tissue culture polystyrenes (TCPs). Gene expression analysis showed that PLLA-Baghdadite had effectively induced osteogenesis-related genes. Taken together, these results suggest that porous nanofiber scaffolds which coated with Baghdadite can enhance osteogenic differentiation of AD-MSC, and PLLA-Baghdadite can be used as a new biodegradable scaffold for bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1284-1293, 2019.

Controlled delivery of biological cues through synthetic scaffolds to enhance the healing capacity of bone defects is yet to be realized clinically. The purpose of this study was development of a bioactive tissue-engineered scaffold providing the sustained delivery of an osteoinductive drug, dexamethasone disodium phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous baghdadite (BD; Ca3 ZrSi2 O9 ) scaffolds, a zirconia-modified calcium silicate ceramic, was coated with DXP-encapsulated CN nanoparticles (DXP-CN) using nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer concentrations were optimized to achieve a homogeneous distribution of hydrogel coating within BD scaffolds. Dynamic laser scattering indicated an average size of 521 ± 21 nm for the DXP-CN nanoparticles. In vitro drug-release studies demonstrated that the developed DXP-CN-GX hydrogel-coated BD scaffolds (DXP-CN-GX-BD) resulted in a sustained delivery of DXP over the 5 days (78 ± 6% of drug release) compared with burst release over 1 h, seen from free DXP loaded in uncoated BD scaffolds (92 ± 8% release in 1 h). To estimate the influence of controlled delivery of DXP from the developed scaffolds, the effect on MG 63 cells was evaluated using various bone differentiation assays. Cell culture within DXP-CN-GX-BD scaffolds demonstrated a significant increase in the expression of early and late osteogenic markers of alkaline phosphatase activity, collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The results suggest that the DXP-releasing nanostructured hydrogel integrated within the BD scaffold caused sustained release of DXP, improving the potential for osteogenic differentiation. Copyright © 2015 John Wiley & Sons, Ltd.

Microstructure-elasticity relations for bone tissue engineering scaffolds are key to rational biomaterial design. As a contribution thereto, we here report comprehensive length measuring, weighing, and ultrasonic tests at 0.1MHz frequency, on porous baghdadite (Ca3ZrSi2O9) scaffolds. The resulting porosity-stiffness relations further confirm a formerly detected, micromechanically explained, general relationship for a great variety of different polycrystals, which also allows for estimating the zero-porosity case, i.e. Young modulus and Poisson ratio of pure (dense) baghdadite. These estimates were impressively confirmed by a physically and statistically independent nanoindentation campaign comprising some 1750 indents. Consequently, we can present a remarkably complete picture of porous baghdadite elasticity across a wide range of porosities, and, thanks to the micromechanical understanding, reaching out beyond classical elasticity, towards poroelastic properties, quantifying the effect of pore pressure on the material system behavior.

Ca3ZrSi2O9 (baghdadite) has become a major research focus within the biomaterial community due to its remarkable in-vitro and in-vivo bioactivity. Although baghdadite seems to exhibit interesting biological properties, as yet there has been no data published concerning its mechanical properties. This lack of knowledge hinders targeting this novel bioactive material towards potential applications. In this study we prepare dense Ca3ZrSi2O9 bulk ceramics for the first time, allowing the evaluation of its mechanical properties including hardness, bending strength, Young׳s modulus, and fracture toughness. The preparation of baghdadite has been accomplished by a direct solid-state synthesis in combination with conventional sintering at 1350-1450°C for 3h. Our results show that samples sintered at 1400°C exhibit the best mechanical properties, resulting in a bending strength, fracture toughness, and hardness of 98±16MPa, 1.3±0.1MPam(0.5), and 7.9±0.2GPa. With a comparable mechanical strength to hydroxyapatite, but with an increased fracture toughness by 30% and hardness by 13% baghdadite is highly suitable for potential applications in non-load bearing areas (e.g. coatings or filler materials).