A challenge in the extrusion-based bioprinting is to find a bioink with optimal biological and physicochemical properties. The aim of this study was to evaluate the influence of wood-based cellulose nanofibrils (CNF) and bioactive glass (BaG) on the rheological properties of gelatin–alginate bioinks and the initial responses of bone cells embedded in these inks. CNF modulated the flow behavior of the hydrogels, thus improving their printability. Chemical characterization by SEM-EDX and ion release analysis confirmed the reactivity of the BaG in the hydrogels. The cytocompatibility of the hydrogels was shown to be good, as evidenced by the viability of human osteoblast-like cells (Saos-2) in cast hydrogels. For bioprinting, 4-layer structures were printed from cell-containing gels and crosslinked with CaCl2. Viability, proliferation and alkaline phosphatase activity (ALP) were monitored over 14 d. In the BaG-free gels, Saos-2 cells remained viable, but in the presence of BaG the viability and proliferation decreased in correlation with the increased viscosity. Still, there was a constant increase in the ALP activity in all the hydrogels. Further bioprinting experiments were conducted using human bone marrow-derived mesenchymal stem cells (hBMSCs), a clinically relevant cell type. Interestingly, hBMSCs tolerated the printing process better than Saos-2 cells and the ALP indicated BaG-stimulated early osteogenic commitment. The addition of CNF and BaG to gelatin–alginate bioinks holds great potential for bone tissue engineering applications.
The crystallization kinetics of the two commercial bioactive glasses, 45S5 and S53P4, was studied using differential thermal analysis (DTA), optical microscopy, and scanning electron microscopy (SEM). The thermal properties, the activation energy of crystallization, and the Johnson‐Mehl‐Avrami (JMA) exponent were determined for two glass fractions: fine powder (<45 μm) and coarse powder (300–500 μm). The crystallization behavior of 45S5 was significantly different for the two fractions, whereas the particle size did not affect the crystallization behavior of S53P4. The JMA exponent of S53P4 suggested surface crystallization for both size fractions. However, for 45S5, the JMA exponent suggested that, with increasing particle size, crystallization evolves from predominantly surface crystallization to predominantly bulk crystallization. Surprisingly, SEM imaging did not support this conclusion. A method based on the crystallization rate dα/dt showed that the JMA approach could not be employed for 45S5. The crystallization mechanism of 45S5 appears to be more complex than a simple nucleation and growth process. Nucleation‐like curves were measured for both fractions of the two glasses. The maximum nucleation rate occurred at 566 ± 4°C and 608 ± 4°C for the coarse powders of 45S5 and S53P4, respectively. The higher maximum nucleation temperature of S53P4 was attributed to the higher SiO2 content. The nucleation temperature range of these two glasses together with DTA data makes it possible to develop guidelines for tailoring thermal treatment parameters to achieve desired glass‐to‐crystal ratios.
Bioactive glasses exhibit the unique ability of bone bonding, thus creating a stable interface by stimulating bone cells toward mechanisms of regeneration and self‐repair activated by ionic dissolution products. Therefore, 3D glass‐derived scaffolds can be considered ideal porous templates to be used in bone tissue engineering strategies and regenerative medicine. This review provides a comprehensive overview of all technological aspects relevant to the fabrication of bioactive glass scaffolds, including the fundamentals of materials processing, a summary of the conventional porogen, and template‐based methods and of recent additive manufacturing technologies, which are promising for large‐scale production of highly reproducible and reliable implants suitable for a wide range of clinical applications.
Commercial melt-quenched bioactive glasses consist of the oxides of silicon, phosphorus, calcium and sodium. Doping of the glasses with oxides of some other elements is known to affect their capability to support hydroxyapatite formation and thus bone tissue healing but also to modify their high temperature processing parameters. In the present study, the influence of gradual substitution of SrO for CaO on the properties of the bioactive glass S53P4 was studied. Thermal analysis and hot stage microscopy were utilized to measure the thermal properties of the glasses. The in vitro bioactivity and solubility was measured by immersing the glasses in simulated body fluid for 6 h to 1 week. The formation of silica rich and hydroxyapatite layers was assessed from FTIR spectra analysis and SEM images of the glass surface. Increasing substitution of SrO for CaO decreased all characteristic temperatures and led to a slightly stronger glass network. The initial glass dissolution rate increased with SrO content. Hydroxyapatite layer was formed on all glasses but on the SrO containing glasses the layer was thinner and contained also strontium. The results suggest that substituting SrO for CaO in S53P4 glass retards the bioactivity. However, substitution greater than 10 mol% allow for precipitation of a strontium substituted hydroxyapatite layer.
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