Chemical Engineering / Kimya Mühendisliği
Permanent URI for this collectionhttps://hdl.handle.net/11147/14
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Article Citation - WoS: 28Citation - Scopus: 29Development of a High-Flux Thin-Film Composite Nanofiltration Membrane With Sub-Nanometer Selectivity Using a Ph and Temperature-Responsive Pentablock Co-Polymer(American Chemical Society, 2019) Bar, Canbike; Çağlar, Nagahan; Uz, Metin; Mallapragada, Surya K.; Alsoy Altınkaya, SacideProducing block co-polymer-based nanofiltration (NF) membranes with sharp molecular weight cutoffs via an efficient method exhibiting persistent size-based separation quality is challenging. In this study, this challenge was addressed by reporting a facile approach to fabricate pentablock co-polymer (PBC)-based thin-film composite (TFC) NF membranes. The PBC, consisting of temperature-responsive Pluronic F127 (PEO-b-PPO-b-PEO) middle blocks and pH-responsive poly(N,N-(diethylamino)ethyl methacrylate) end blocks, were synthesized by atom-transfer radical polymerization. This polymer was then attached electrostatically to the surface of polysulfone/sulfonated polyether-sulfone support membranes fabricated using a non-solvent-induced phase separation technique. The conformational changes of the PBC chains in response to pH and temperature determined the, pure water flux and neutral solute (PEG 1000) rejection performance of TFC membranes. Permeability of the membranes increased from 13.0 +/- 0.63 to 15.9 +/- 0.06 L/m(2).h bar and from 6.7 +/- 0.00 to 13.9 +/- 0.07 L/m(2).h.bar by changing the solution pH from 4 to 8.5 and temperature from 4 to 25 degrees C, respectively. The pH- and temperature-responsive conformational changes did not affect the PEG 1000 rejection and membrane pore radius, which remained constant at similar to 89% and similar to 0.9 nm, respectively. This important finding was attributed to the high grafting density of co-polymer chains, resulting in spatial limitations among the grafted chains. The pore size of similar to 0.9 nm achieved with the proposed membrane design is the smallest size reported so far for membranes fabricated from block copolymers. TFC membranes demonstrated high stability and maintained their flux and rejection values under both static (storage in an acidic solution for up to 1 month) and dynamic (filtering PEG 1000 solution over 1 week) conditions. Pentablock copolymers enable a NF membrane with a sharp molecular weight cutoff suitable for size-selective separations. The membrane fabrication technique proposed in this study is a scalable and promising alternative that does not involve complex synthetic routes.Article Citation - WoS: 40Citation - Scopus: 47Gelatin-Based 3d Conduits for Transdifferentiation of Mesenchymal Stem Cells Into Schwann Cell-Like Phenotypes(Elsevier Ltd., 2017) Uz, Metin; Büyüköz, Melda; Sharma, Anup D.; Sakaguchi, Donald S.; Alsoy Altınkaya, Sacide; Mallapragada, Surya K.In this study, gelatin-based 3D conduits with three different microstructures (nanofibrous, macroporous and ladder-like) were fabricated for the first time via combined molding and thermally induced phase separation (TIPS) technique for peripheral nerve regeneration. The effects of conduit microstructure and mechanical properties on the transdifferentiation of bone marrow-derived mesenchymal stem cells (MSCs) into Schwann cell (SC) like phenotypes were examined to help facilitate neuroregeneration and understand material-cell interfaces. Results indicated that 3D macroporous and ladder-like structures enhanced MSC attachment, proliferation and spreading, creating interconnected cellular networks with large numbers of viable cells compared to nanofibrous and 2D-tissue culture plate counterparts. 3D-ladder-like conduit structure with complex modulus of ∼0.4 × 106 Pa and pore size of ∼150 μm provided the most favorable microenvironment for MSC transdifferentiation leading to ∼85% immunolabeling of all SC markers. On the other hand, the macroporous conduits with complex modulus of ∼4 × 106 Pa and pore size of ∼100 μm showed slightly lower (∼65% for p75, ∼75% for S100 and ∼85% for S100β markers) immunolabeling. Transdifferentiated MSCs within 3D-ladder-like conduits secreted significant amounts (∼2.5 pg/mL NGF and ∼0.7 pg/mL GDNF per cell) of neurotrophic factors, while MSCs in macroporous conduits released slightly lower (∼1.5 pg/mL NGF and 0.7 pg/mL GDNF per cell) levels. PC12 cells displayed enhanced neurite outgrowth in media conditioned by conduits with transdifferentiated MSCs. Overall, conduits with macroporous and ladder-like 3D structures are promising platforms in transdifferentiation of MSCs for neuroregeneration and should be further tested in vivo. Statement of Significance This manuscript focuses on the effect of microstructure and mechanical properties of gelatin-based 3D conduits on the transdifferentiation of mesenchymal stem cells to Schwann cell-like phenotypes. This work builds on our recently accepted manuscript in Acta Biomaterialia focused on multifunctional 2D films, and focuses on 3D microstructured conduits designed to overcome limitations of current strategies to facilitate peripheral nerve regeneration. The comparison between conduits fabricated with nanofibrous, macroporous and ladder-like microstructures showed that the ladder-like conduits showed the most favorable environment for MSC transdifferentiation to Schwann-cell like phenotypes, as seen by both immunolabeling as well as secretion of neurotrophic factors. This work demonstrates the importance of controlling the 3D microstructure to facilitate tissue engineering strategies involving stem cells that can serve as promising approaches for peripheral nerve regeneration.Article Citation - WoS: 65Citation - Scopus: 72Effect of Peg Grafting Density and Hydrodynamic Volume on Gold Nanoparticle-Cell Interactions: an Investigation on Cell Cycle, Apoptosis, and Dna Damage(American Chemical Society, 2016) Uz, Metin; Bulmuş, Volga; Alsoy Altınkaya, SacideIn this study, interactions of polyethylene glycol (PEG)-coated gold nanoparticles (AuNPs) with cells were investigated with particular focus on the relationship between the PEG layer properties (conformation, grafting density, and hydrodynamic volume) and cell cycle arrest, apoptosis, and DNA damage. Steric hindrance and PEG hydrodynamic volume controlled the protein adsorption, whereas the AuNP core size and PEG hydrodynamic volume were primary factors for cell uptake and viability. At all PEG grafting densities, the particles caused significant cell cycle arrest and DNA damage against CaCo2 and PC3 cells without apoptosis. However, at a particular PEG grafting density (∼0.65 chains/nm2), none of these severe damages were observed on 3T3 cells indicating discriminating behavior of the healthy (3T3) and cancer (PC3 and CaCo2) cells. It was concluded that the PEG grafting density and hydrodynamic volume, tuned with the PEG concentration and AuNP size, played an important role in particle-cell interactions.
