Noggin promotes osteogenesis in human adipose-derived mesenchymal stem cells via FGFR2/Src/Akt and ERK signaling pathway.

The balance between Noggin and bone morphogenetic proteins (BMPs) is important during early development and skeletal regenerative therapies. Noggin binds BMPs in the extracellular space, thereby preventing BMP signaling. However, Noggin may affect cell response not necessarily through the modulation of BMP signaling, raising the possibility of direct Noggin signaling through yet unspecified receptors. Here we show that in osteogenic cultures of adipose-derived stem cells (ASCs), Noggin activates fibroblast growth factor receptors (FGFRs), Src/Akt and ERK kinases, and it stabilizes TAZ proteins in the presence of dexamethasone. Overall, this leads ASCs to increased expression of osteogenic markers and robust mineral deposition. Our results also indicate that Noggin can induce osteogenic genes expression in normal human bone marrow stem cells and alkaline phosphatase activity in normal human dental pulp stem cells. Besides, Noggin can specifically activate FGFR2 in osteosarcoma cells. We believe our findings open new research avenues to further explore the involvement of Noggin in cell fate modulation by FGFR2/Src/Akt/ERK signaling and potential applications of Noggin in bone regenerative therapies.

Chemical Compounds Released from Specific Osteoinductive Bioactive Materials Stimulate Human Bone Marrow Mesenchymal Stem Cell Migration.

In this work, a poly(L-lactide-co-glycolide) (PLGA)-based composite was enriched with one of the following sol-gel bioactive glasses (SBG) at 50 wt.%: A1-40 mol% SiO2, 60 mol% CaO, CaO/SiO2 ratio of 1.50; S1-80 mol% SiO2, 20 mol% CaO, CaO/SiO2 ratio of 0.25; A2-40 mol% SiO2, 54 mol% CaO, 6 mol% P2O5, CaO/SiO2 ratio of 1.35; S2-80 mol% SiO2,16 mol% CaO, 4 mol% P2O5, CaO/SiO2 ratio of 0.20. The composites and PLGA control sheets were then soaked for 24 h in culture media, and the obtained condition media (CM) were used to treat human bone marrow stromal cells (hBMSCs) for 72 h. All CMs from the composites increased ERK 1/2 activity vs. the control PLGA CM. However, expressions of cell migration-related c-Fos, osteopontin, matrix metalloproteinase-2, C-X-C chemokine receptor type 4, vascular endothelial growth factor, and bone morphogenetic protein 2 were significantly increased only in cells treated with the CM from the A1/PLGA composite. This CM also significantly increased the rate of human BMSC migration but did not affect cell metabolic activity. These results indicate important biological markers that are upregulated by products released from the bioactive composites of a specific chemical composition, which may eventually prompt osteoprogenitor cells to colonize the bioactive material and accelerate the process of tissue regeneration.

Microstructure and In Vitro Evaluation of Extruded and Hot Drawn Alloy MgCa0.7 for Biodegradable Surgical Wires.

The MgCa0.7 alloy may be a promising material for biodegradable surgical wires. In this paper, the technology for producing surgical wires from this alloy has been developed, based both on finite element modelling and experimental study. In particular, the extrusion and hot-drawing effects on the mechanical properties, microstructures, in-vitro rates of biocorrosion, and cytotoxicity to human cancer cells (SaOS-2) and healthy (hPDL) ones, have been determined. An approximately 30-40% increase in corrosion rate due to increasing hot-drawing temperature was observed. An effect of hot-drawing temperature on cytotoxicity was also found. Notably, at various stages of the final wires' production, the MgCa0.7 alloy became toxic to cancer cells. This cytotoxicity depended on the alloys' processing parameters and was maximal for the as-extruded rod and for the wires immediately after hot drawing at 440 °C. Thus, the careful selection of processing parameters makes it possible to obtain a product that is not only a promising candidate for biodegradable surgical wires, but one which also has intrinsic bioactive properties that produce antitumor activity.

In vitro cytotoxicity of biodegradable Zn-Mg surgical wires in tumor and healthy cells.

In this work, we examined the in vitro cytotoxicity of new biodegradable surgical wires. The wires made of zinc with the addition of a small amount of magnesium (pure zinc, ZnMg 0.0026, ZnMg 0.0068, and ZnMg 0.08) have been investigated. The wires were produced using a technology based on extrusion and subsequent drawing. The resulting wires with a diameter of 0.8-1.0 mm are designed to be used in surgical operations related to bone joints. For cytotoxicity studies, we have selected human dental pulp stem cells (hDPSC) as the cell population representing normal osteoprogenitor cells. Considering that, after bone surgeries, the chance of osteosarcoma increases, we have compared the results obtained in hDPSC to those obtained with Saos-2 human osteosarcoma cell line. Cultured cells were exposed to the extracts obtained from the materials incubated in culture medium for 24 h with and without preincubation. Extracts of different ratios were examined. The results showed that the extracts obtained from wires made of ZnMg 0.0026 alloy exhibit high toxicity to Saos-2 osteosarcoma cells and low toxicity to hDPSC cells. This was in contrast to all reference materials, i.e., commercial surgical sutures made of steel and polymers, that did not display cytotoxicity toward osteosarcoma cells. Thus, the detected phenomenon for the ZnMg 0.0026 alloy can become the basis for creating biodegradable Zn-Mg surgical wires with antitumor activity.

Antibacterial Activity and Cytocompatibility of Bone Cement Enriched with Antibiotic, Nanosilver, and Nanocopper for Bone Regeneration.

Bacterial infections due to bone replacement surgeries require modifications of bone cement with antibacterial components. This study aimed to investigate whether the incorporation of gentamicin or nanometals into bone cement may reduce and to what extent bacterial growth without the loss of overall cytocompatibility and adverse effects in vitro. The bone cement Cemex was used as the base material, modified either with gentamicin sulfate or nanometals: Silver or copper. The inhibition of bacterial adhesion and growth was examined against five different bacterial strains along with integrity of erythrocytes, viability of blood platelets, and dental pulp stem cells. Bone cement modified with nanoAg or nanoCu revealed greater bactericidal effects and prevented the biofilm formation better compared to antibiotic-loaded bone cement. The cement containing nanoAg displayed good cytocompatibility without noticeable hemolysis of erythrocytes or blood platelet disfunction and good viability of dental pulp stem cells (DPSC). On the contrary, the nanoCu cement enhanced hemolysis of erythrocytes, reduced the platelets aggregation, and decreased DPSC viability. Based on these studies, we suggest the modification of bone cement with nanoAg may be a good strategy to provide improved implant fixative for bone regeneration purposes.