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When sessile nanofluid droplets evaporate, solid nanoparticles can be organized in a wide variety of patterns on the substrate. The composition of the nanofluid, internal flow type of droplet and the rate of drying affect drop geometry, and the final pattern. Using poly(lactic-co-glycolic acid)-block-poly(ethylene glycol)(PLGA-b-PEG) as the example, we produced micro-stripe patterning from nanoparticles by drying of sessile fluid droplets. We investigated the nanoparticle properties and flow dynamics to clarify their effects on the patterning. Nanoparticles were prepared by hydrodynamic flow focusing using a T-junction microfluidic device with high production efficiency and the ability to generate an extremely narrow size distribution. PLGA-b-PEG was prepared as oil phase in acetonitrile and water/oil flow rate was changed from 1 to 3 at constant oil phase flow rate (50 μL/min). Then, nanofluid was collected on the surface as sessile droplets within acetonitrile/water binary dispersed phase. Depending on size, charge and size-distribution, the nanoparticles deposited on the surface exhibited various patterns. Dynamic Light and X-ray Scattering measurements showed that, approximately 100 nm particles with relatively low PDI (0.04) were produced for the first time in surfactant free conditions in a microfluidic device and they generated self-assembled ordered patterns, which are regulated by the type of internal flow in the sessile nanofluid droplet during sequential evaporation of acetonitrile and water.

Ibuprofen is a non-steroidal anti-inflammatory drug for the treatment of Rheumatoid Arthritis and osteoarthritis. In this study, we prepared topical gel network for enhancement of ibuprofen penetration, maintenance of controlled release and increased patient compliance. Nanoparticles containing ibuprofen were prepared by means of emulsion formation/solvent diffusion method using synthesized copolymer. Nanoparticles were then conjugated with aminoethylmethacrylate, resulting in ibuprofen-loaded nanoparticles in PLGA

This study aimed to develop sorafenib loaded magnetic microspheres for the treatment of hepatocellular carcinoma. To achieve this goal, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised and encapsulated in alginate microspheres together with an antineoplastic agent, sorafenib. In the study, firstly SPIONs were synthesised and characterised by dynamic light scattering, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. Then, alginate-SPIONs microspheres were developed, and further characterised by electron spin resonance spectrometer and vibrating sample magnetometer. Besides the magnetic properties of SPIONs, alginate microspheres with SPIONs were also found to have magnetic properties. The potential use of microspheres in hyperthermia treatment was then investigated and an increase of about 4°C in the environment was found out. Drug release studies and cytotoxicity tests were performed after sorafenib was encapsulated into the magnetic microspheres. According to release studies, sorafenib has been released from microspheres for 8 h. Cytotoxicity tests showed that alginate-SPION-sorafenib microspheres were highly effective against cancerous cells and promising for cancer therapy.

This work focuses on the synthesis of oil-layered microbubbles using two microfluidic T-junctions in series and evaluation of the effectiveness of these microbubbles loaded with doxorubicin and curcumin for cell invasion arrest from 3D spheroid models of triple negative breast cancer (TNBC), MDA-MB-231 cell line. Albumin microbubbles coated in the drug-laden oil layer were synthesized using a new method of connecting two microfluidic T-mixers in series. Double-layered microbubbles thus produced consist of an innermost core of nitrogen gas encapsulated in an aqueous layer of bovine serum albumin (BSA) which in turn, is coated with an outer layer of silicone oil. In order to identify the process conditions leading to the formation of double-layered microbubbles, a regime map was constructed based on capillary numbers for aqueous and oil phases. The microbubble formation regime transitions from double-layered to single layer microbubbles and then to formation of single oil droplets upon gradual change in flow rates of aqueous and oil phases. In vitro dissolution studies of double-layered microbubbles in an air-saturated environment indicated that a complete dissolution of such bubbles produces an oil droplet devoid of a gas bubble. Incorporation of doxorubicin and curcumin was found to produce a synergistic effect, which resulted in higher cell deaths in 2D monolayers of TNBC cells and inhibition of cell proliferation from 3D spheroid models of TNBC cells compared to the control.

Early diagnosis of cancer is the most important factor that increases the success of treatment. Therefore, the development of new diagnostic tools is a necessity. In this study, a new electrode surface was developed via modification of a disposable titanium electrode with anodic oxidation and coating of gold nanoparticle and chitosan. Titanium electrodes were anodized by several anodization parameters to obtain a nanoporous surface and characterized by scanning electron microscopy. Electrodes anodized in optimum conditions were modified with gold nanoparticles and chitosan for enhancing conductivity and functionalizing the surface of electrode, respectively. To detect prostate specific antigen (PSA), anti-PSA was bound onto the functional electrode surface. Modified electrodes were characterized with scanning electron microscopy and cyclic voltammetry and used for chronoamperometric detection of PSA. Limit of detection (LOD) of the designed electrode was found to be 7.8 ng mL-1 for PSA in a linear range of 0 - 100 ng mL-1.

Amphiphilic block copolymers are widely used in science owing to their versatile properties. In this study, amphiphilic block copolymer poly(lactic- co-glycolic acid)- block-poly(ethylene glycol) (PLGA- b-PEG) was used to create microdroplets in a T-junction microfluidic device with a well-defined geometry. To compare interfacial characteristics of microdroplets, dichloromethane (DCM) and chloroform were used to prepare PLGA- b-PEG solution as an oil phase. In the T-junction device, water and oil phases were manipulated at variable flow rates from 50 to 300 μL/min by increments of 50 μL/min. Fabricated microdroplets were directly collected on a glass slide. After a drying period, porous two-dimensional and three-dimensional structures were obtained as honeycomb-like structure. Pore sizes were increased according to increased water/oil flow rate for both DCM and chloroform solutions. Also, it was shown that increasing polymer concentration decreased the pore size of honeycomb-like structures at a constant water/oil flow rate (50:50 μL/min). Additionally, PLGA- b-PEG nanoparticles were also obtained on the struts of honeycomb-like structures according to the water solubility, volatility, and viscosity properties of oil phases, by the aid of Marangoni flow. The resulting structures have a great potential to be used in biomedical applications, especially in drug delivery-related studies, with nanoparticle forming ability and cellular responses in different surface morphologies.

The major focus of this study was to prepare poly(lactic-co-glycolic) acid (PLGA) microspheres containing atorvastatin calcium (ATR) in combination with alpha-lipoic acid (ALA). PLGA microspheres will maintain dual-release for providing neuroprotective effects for peripheral nerve injury. For this purpose, micro spheres were prepared by spray dryer with different drug:polymer ratios. Microsphere formulations were evaluated for particle size distribution, preparation and encapsulation efficiency, surface morphology, in-vitro release and dose dependent cytotoxicity test with L-929 and B-35 cells. TGA, DSC and FTIR analysis were performed for the investigation of physicochemical properties of the PLGA microspheres. Encapsulation efficiencies were calculated as > 70% for ALA and > 62% for ATR. FTIR results indicated that there was no interaction between the polymer and the active ingredients. A novel analytical method has been developed and fully validated, which would allow for quantification of ATR and ALA simultaneously. Release profiles showed that ALA is released within the first 17 h and ATR release lasted for 17 days. Finally, results showed that there was no any toxicity associated with ALA and ATR containing PLGA formulations on both B-35 and L-929 cells. It was concluded that PLGA formulations with dual effects are promising systems for the treatment of peripheral nerve injury. (C) 2017 Elsevier B.V. All rights reserved.

Bayram, Cem/0000-0001-8717-4668; CELIK, EKIN/0000-0003-1966-3907 WOS: 000377737000027 PubMed: 27207058 Peptide based hydrogels gained a vast interest in the tissue engineering studies thanks to great superiorities such as biocompatibility, supramolecular organization without any need of additional crosslinker, injectability and tunable nature. Fmoc-diphenylalanine (FmocFF) is one of the earliest and widely used example of these small molecule gelators that have been utilized in biomedical studies. However, Fmoc-peptides are not feasible for long term use due to low stability and weak mechanical properties at neutral pH. In this study, Fmoc-FF dipeptides were mechanically enhanced by incorporation of alginate, a biocompatible and absorbable polysaccharide. The binary hydrogel is obtained via molecular self-assembly of FmocFF dipeptide in alginate solution followed by ionic crosslinldng of alginate moieties with varying concentrations of calcium chloride. Hydrogel characterization was evaluated in terms of morphology, viscoelastic moduli and diffusional phenomena and the structures were tested as 3D scaffolds for bovine chondrocytes. In vitro evaluation of scaffolds lasted up to 14 days and cell viability, sulphated glycosaminoglycan (sGAG) levels, collagen type II synthesis were determined. Our results showed that alginate incorporation into FmocFF hydrogels leads to better mechanical properties and higher stability with good biocompatibility. (C) 2016 Elsevier B.V. All rights reserved. Hacettepe University Scientific Research Projects Coordination Office (HU-BAP) [1136] This study was supported by the Hacettepe University Scientific Research Projects Coordination Office (HU-BAP, project no: 1136).

Bayram, Cem/0000-0001-8717-4668; CELIK, EKIN/0000-0003-1966-3907 WOS: 000382858400005 Currently, the main focus on tissue engineering strategies is to mimic the extracellular matrix of the related tissues. Many studies accomplished to build tissue scaffolds to act as the natural surroundings of the specific interest, which can be established to behave like either healthy or unhealthy tissues. The latter one of these conditions is a quite new approach and crucial for the design of three-dimensional in vitro disease models. This study investigates the potential of a composite scaffold consisting hydroxyapatite-integrated fluorenyl-9-methoxycarbonyl diphenylalanine hydrogels by focusing on the optimization of this hybrid scaffold for the development of an in vitro model of degenerative cartilage. Cell growth, chondrocyte proliferation, extracellular matrix production, hypertrophy marker monitoring, scaffold mechanical properties, and morphological analysis were evaluated. Fluorenyl-9-methoxycarbonyl diphenylalanine dipeptides were dissolved in null cell culture media and pH decreased sequentially to compel peptides to self-organize into fibrous hydrogel scaffolds. Nano-hydroxyapatite crystals were incorporated into fluorenyl-9-methoxycarbonyl diphenylalanine hydrogels during the gelation to investigate the effect on chondrocytes. It is observed that hydroxyapatite incorporation into peptide hydrogels significantly increased the alkaline phosphatase activity and assymetrical cell divisions, which is appraised as an outcome of chondrocyte hypertrophy. It is concluded that chondrocytes develop a hypertrophic potential when they are cultured in a media with nano-hydroxyapatites in a three-dimensional cell culture matrix mimicking the extracellular matrix conditions of degenerative cartilage.

WOS: 000472241700072 PubMed ID: 31147048 Degenerative cartilage is the pathology of severe depletion of extracellular matrix components in articular cartilage. In diseases like osteoarthritis, misregulation of microRNAs contributes the pathology and collectively leads to disruption of the homeostasis. In this study chondroitin sulfate/hyaluronic acid/chitosan nanoparticles were prepared and successfully characterized chemically and morphologically. Results demonstrated higher chondroitin sulfate amounts led smaller nanoparticles, but lower surface zeta potential due to high electronegativity. After optimization of chondroitin sulfate amounts regarding size and charge, nanoparticles were loaded with microRNA-149-5p, a therapeutic miRNA downregulated in osteoarthritis, and evaluated focusing on their loading efficiency, release behaviour, cytotoxicity and gene transfection efficiency in vitro. Results showed all nanoparticle formulations were non-toxic and promising gene delivery agents, due to increased levels of microRNA-149-5p and decreased mRNA levels of microRNA's target, FUT-1. Highest gene transfection efficiency was obtained with the nanoparticle formulation which had the highest chondroitin sulfate load and smallest size. In addition, owing to their high chondroitin sulfate cargo, all nanoparticles were reported to enhance chondrogenesis, which was demonstrated by gene expression analysis and sulfated glycosaminoglycan (sGAG) staining. The obtained data suggest that the delivery of microRNA-149-5p via polysaccharide based carriers could achieve collaborative impact in cartilage regeneration and have a potential to enhance osteoarthritis treatment.

The control of pore size and uniform porosity remains as an important challenge in gelatin scaffolds. The precise control in building blocks of tissue scaffolds without any additional porogen is possible with costly equipment and techniques, though some pre‐requirements for polymeric material, such as photo‐polymerizability or sintering ability, may be needed prior to construction. Herein, a method for the fabrication of gelatin scaffolds with homogenous porosity using simple T‐junction microfluidics is described. The size of the microbubbles is precisely controlled with 5% deviation from the average. Porous gelatin scaffolds are obtained by building‐up the monodispersed microbubbles in dilute cross‐linker solutions. The effect of cross‐linker density on pore diameter is also investigated. After cross‐linking, pore size of the resultant five scaffold groups are precisely controlled as 135 ± 11, 193 ± 11, 216 ± 9, 231 ± 5, and 250 ± 12 µm. Porosity ratios above 65% are achieved in every sample group. According to the cell culture experiments, structures support high cell adhesion, viability, and migration through the porous network via interconnectivity. This study offers a practical and economical approach for the preparation of porous gelatin scaffolds with homogenous porosity which can be utilized in diverse tissue engineering applications.

WOS: 000282277300025, PubMed: 20844318, 316L-type stainless steel is a raw material mostly used for manufacturing metallic coronary stents. The purpose of this study was to examine the chemical, wettability, cytotoxic and haemocompatibility properties of 316L stainless steel stents which were modified by plasma polymerization. Six different polymeric compounds, polyethylene glycol, 2-hydroxyethyl methacrylate, ethylenediamine, acrylic acid, hexamethyldisilane and hexamethyldisiloxane, were used in a radio frequency glow discharge plasma polymerization system. As a model antiproliferative drug, mitomycin-C was chosen for covalent coupling onto the stent surface. Modified SS 316L stents were characterized by water contact angle measurements (goniometer) and x-ray photoelectron spectroscopy. C1s binding energies showed a good correlation with the literature. Haemocompatibility tests of coated SS 316L stents showed significant latency (t-test, p < 0.05) with respect to SS 316L and control groups in each test., Scientific and Technological Research Council of Turkey; Health Sciences Research Group (SBAG) [106S182], This work was funded by The Scientific and Technological Research Council of Turkey, Health Sciences Research Group (SBAG) project number 106S182. Additionally, the stents used in this study were kindly gifted by Alvimedica Medical Inc., Turkey.