3D printing of alginate dialdehyde-gelatin (ADA-GEL) hydrogels incorporating phytotherapeutic icariin loaded mesoporous SiO2-CaO nanoparticles for bone tissue engineering.

3D printing enables a better control over the microstructure of bone restoring constructs, addresses the challenges seen in the preparation of patient-specific bone scaffolds, and overcomes the bottlenecks that can appear in delivering drugs/growth factors promoting bone regeneration. Here, 3D printing is employed for the fabrication of an osteogenic construct made of hydrogel nanocomposites. Alginate dialdehyde-gelatin (ADA-GEL) hydrogel is reinforced by the incorporation of bioactive glass nanoparticles, i.e. mesoporous silica-calcia nanoparticles (MSNs), in two types of drug (icariin) loading. The composites hydrogel is printed as superhydrated composite constructs in a grid structure. The MSNs not only improve the mechanical stiffness of the constructs but also induce formation of an apatite layer when the construct is immersed in simulated body fluid (SBF), thereby promoting cell adhesion and proliferation. The nanocomposite constructs can hold and deliver icariin efficiently, regardless of its incorporation mode, either as loaded into the MSNs or freely distributed within the hydrogel. Biocompatibility tests showed that the hydrogel nanocomposites assure enhanced osteoblast proliferation, adhesion, and differentiation. Such optimum biological properties stem from the superior biocompatibility of ADA-GEL, the bioactivity of the MSNs, and the supportive effect of icariin in relation to cell proliferation and differentiation. Taken together, given the achieved structural and biological properties and effective drug delivery capability, the hydrogel nanocomposites show promising potential for bone tissue engineering.

Synthesis, Characterization, Antibacterial Properties, and In Vitro Studies of Selenium and Strontium Co-Substituted Hydroxyapatite.

In this study, as a measure to enhance the antimicrobial activity of biomaterials, the selenium ions have been substituted into hydroxyapatite (HA) at different concentration levels. To balance the potential cytotoxic effects of selenite ions (SeO32-) in HA, strontium (Sr2+) was co-substituted at the same concentration. Selenium and strontium-substituted hydroxyapatites (Se-Sr-HA) at equal molar ratios of x Se/(Se + P) and x Sr/(Sr + Ca) at (x = 0, 0.01, 0.03, 0.05, 0.1, and 0.2) were synthesized via the wet precipitation route and sintered at 900 °C. The effect of the two-ion concentration on morphology, surface charge, composition, antibacterial ability, and cell viability were studied. X-ray diffraction verified the phase purity and confirmed the substitution of selenium and strontium ions. Acellular in vitro bioactivity tests revealed that Se-Sr-HA was highly bioactive compared to pure HA. Se-Sr-HA samples showed excellent antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus carnosus) bacterial strains. In vitro cell-material interaction, using human osteosarcoma cells MG-63 studied by WST-8 assay, showed that Se-HA has a cytotoxic effect; however, the co-substitution of strontium in Se-HA offsets the negative impact of selenium and enhanced the biological properties of HA. Hence, the prepared samples are a suitable choice for antibacterial coatings and bone filler applications.

Osteogenic properties of manganese-doped mesoporous bioactive glass nanoparticles.

Mesoporous bioactive glass nanoparticles (MBGNs) based on the SiO2 -P2 O5 -CaO system have demonstrated promising properties for the local delivery of therapeutically active ions with the aim to improve their osteogenic properties. Manganese (Mn) has been identified as a candidate ion for local application in bone tissue engineering applications. It remains unknown how SiO2 -P2 O5 -CaO-based MBGNs influence human bone marrow-derived mesenchymal stromal cells (BMSCs) in terms of viability, proliferation, and differentiation and how these features can be modified by the addition of Mn to the MBGNs' composition. Therefore, in this study, MBGNs (composition in mol%: 50 SiO2 , 40 CaO, 10 P2 O5 ) and its Mn-doped derivate 5Mn-MBGNs (composition in mol%: 50 SiO2 , 35 CaO, 10 P2 O5 , 5 MnO) were applied to a culture of BMSCs in two different concentrations. With increasing concentration, 5Mn-MBGNs supported osteogenic differentiation and enhanced the upregulation of genes encoding for extracellular matrix proteins but also negatively influenced cell viability and proliferation. When applied in lower concentrations, MBGNs showed not only viability- and growth-enhancing effects but also significant pro-osteogenic features-however, these positive properties deteriorated with increasing concentration. Two major conclusions can be drawn from this study: (a) supplementation with Mn enhances the osteogenic properties of MBGNs in a dose-dependent manner and (b) MBGNs constitute an attractive vector for therapeutically active ions since it exhibits an intrinsic pro-osteogenic potential that can be improved and/or modified by incorporation of therapeutically active ions. Future studies should focus on the evaluation of further candidate ions that are known to influence osteogenic differentiation positively.