Nanoparticles (NPs) have a greater potential to travel through an organism via inhalation than any other larger particles, and could be more toxic due to their larger surface area and specific structural/chemical properties. The aim of this study was to evaluate in vitro biological effects of various inhalable metallic NPs (TiO2, Ag, Al, Zn, Ni). Human alveolar epithelial cells (A549) were exposed to various concentrations of NPs for 24 h. The extent of morphological damage was in the order of m-TiO2 > n-TiO2 > m-silica >> n-Ni approximately = n-Zn approximately = n-Ag approximately = n-Al and was affected in a dose-dependent manner. The extent of apoptotic damage measured with two-color flow cytometry was in the order of n-Zn > n- Ni > m-silica >> n- TiO2 > m- TiO2 > n-Al > n-Ag. The extent of apoptotic damage measured with DNA fragmentation was in the order of n-Zn approximately = m-silica > n- Ni >> m- TiO2 approximately = n- TiO2 approximately = n-Al > n-Ag, indicating no significant difference in the damages by both m-TiO2 and n-TiO2. The extents of apoptotic damages were also affected in a dose-dependent manner. Uptake of no other NPs but n-TiO2 and m-TiO2 into the cells was observed after 24 h exposure. The intracellular generation of ROS was significant with n-Zn but not with the other particles. These results demonstrated that various inhalable metallic NPs (TiO2, Ag, Al, Zn, Ni) could cause cell damages directly or indirectly. More detailed studies on the influence of size, structure, and composition of the NPs are needed to better understand their toxic mechanisms.
We developed a novel pH- and thermo-sensitive hydrogel as a scaffold for autologous bone tissue engineering. We synthesized this polymer by adding pH-sensitive sulfamethazine oligomers (SMOs) to both ends of a thermo-sensitive poly(epsilon-caprolactone-co-lactide)-poly(ethylene glycol)-poly(epsilon-caprolactone-co-lactide) (PCLA-PEG-PCLA) block copolymer, yielding a pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer. The synthesized block copolymer solution rapidly formed a stable gel under physiological conditions (pH 7.4 and 37 degrees C), whereas it formed a sol at pH 8.0 and 37 degrees C, making it injectable. This pH/thermo-sensitive hydrogel exhibited high biocompatibility in a Dulbecco's modified Eagle's medium extract test. Under physiological conditions, the hydrogel easily encapsulated human mesenchymal stem cells (hMSCs) and recombinant human bone morphogenetic protein-2 (rhBMP-2), with encapsulating efficiencies of about 90% and 85%, respectively. To assay for ectopic bone formation in vivo, we subcutaneously injected a polymer solution containing hMSCs and rhBMP-2 into the back of mice, after which we could observe hMSC differentiation for up to 7 weeks. Histological studies revealed mineralized tissue formation and high levels of alkaline phosphatase activity in the mineralized tissue. Therefore, this pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer demonstrated potential as an injectable scaffold for bone tissue engineering, with in situ formation capabilities.
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