Browsing by Subject "Biomedical applications"
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Item Open Access Biomedical applications of peptide nanostructures(2016-04) Şardan Ekiz, MelisThesis (Ph. D.): Bilkent University, Materials Science and Nanotechnology Program, İhsan Doğramacı Bilkent University, 2016.Item Open Access Catalytic and bioactive nanostructures for regenerative medicine applications(2016-04) Gülseren, GülcihanPeptide nanostructures provide a remarkable toolbox for designing nature inspired smart materials. Synthetic peptide nanomaterials can be tailored with chemical, physical and biological signals to be utilized in a wide range of applications in biomedicine. With the increasing demand for complex nanostructures with facile preparation methods, bioinspired smart nanomaterials have gained more importance for achieving multifunctional hybrid materials. In particular, biological or chemical cues can be integrated into supramolecular designs to generate bioactive materials. This thesis describes nature inspired combinatorial methods for designing peptide nanostructures, which display catalytic and biologically functional moieties. These multifunctional peptide nanostructures were synthesized by using solid phase peptide synthesis. Designed peptide units were in accordance with the relevant biological function and they self-assemble to form nanofibrous networks mimicking the extracellular matrix. This combinatorial approach allows a wide range of applications including artificial catalysis, cell cultivation, biomineralization and live-cell labeling. In this thesis, the self-assembled catalytic and bioactive peptide nanostructures were utilized in artificial enzyme studies, biomineralization and tissue regeneration. The results show that these new artificial enzymes display both catalytic and biological functions of their natural counterparts such as proteins. In the first chapter, basic concepts of self-assembly, artificial catalysis approach, biomineralization and bioactive peptide nanostructures were explained. In the second chapter, multicomponent artificial catalyst model formed by self-assembly was investigated. Designed artificial peptide molecules were characterized structurally and catalytic capability of this de novo system was shown with both model and actual substrate. In the third chapter, ALP inspired catalytic, ion coordinating and biomineralizable peptide nanostructures were examined, bioactivity of this enzyme inspired materials was shown with multiple cell lines and using 2D and 3D cell culture methods. In the fourth chapter, enzyme responsive dentin sialophospho-protein like materials were exhibited instead artificial catalyst. Multi-responsive material induced biomineralization similar to dentin sialophospho-protein which controls mineralization during dentinogenesis. In the fifth part, peptide nanostructures were applied as bioorthogonal catalyst for live-cell tagging study, fluorophore tagged living cells by peptide catalyst was imaged by confocal microscopy. The last chapter covers novel materials inspired by unique nature of collagen and its bioregenerative capacity investigated with stem cells and preliminary cartilage induction was obtained.Item Open Access Design and fabrication of auxetic PCL nanofiber membranes for biomedical applications(Elsevier, 2017-12) Bhullar, S. K.; Rana, D.; Lekesiz, H.; Bedeloglu, A. C.; Ko, J.; Cho, Y.; Aytac Z.; Uyar, Tamer; Jun, M.; Ramalingam, M.The main objective of this study was to fabricate poly (ε-caprolactone) (PCL)-based auxetic nanofiber membranes and characterize them for their mechanical and physicochemical properties. As a first step, the PCL nanofibers were fabricated by electrospinning with two different thicknesses of 40 μm (called PCL thin membrane) and 180 μm (called PCL thick membrane). In the second step, they were tailored into auxetic patterns using femtosecond laser cut technique. The physicochemical and mechanical properties of the auxetic nanofiber membranes were studied and compared with the conventional electrospun PCL nanofibers (non-auxetic nanofiber membranes) as a control. The results showed that there were no significant changes observed among them in terms of their chemical functionality and thermal property. However, there was a notable difference observed in the mechanical properties. For instance, the thin auxetic nanofiber membrane showed the magnitude of elongation almost ten times higher than the control, which clearly demonstrates the high flexibility of auxetic nanofiber membranes. This is because that the auxetic nanofiber membranes have lesser rigidity than the control nanofibers under the same load which could be due to the rotational motion of the auxetic structures. The major finding of this study is that the auxetic PCL nanofiber membranes are highly flexible (10-fold higher elongation capacity than the conventional PCL nanofibers) and have tunable mechanical properties. Therefore, the auxetic PCL nanofiber membranes may serve as a potent material in various biomedical applications, in particular, tissue engineering where scaffolds with mechanical cues play a major role.Item Open Access Examination of fabrication conditions of acrylate-based hydrogel formulations for doxorubicin release and efficacy test for hepatocellular carcinoma cell(Taylor and Francis., 2014) Bayramoglu, G.; Gozen, Damla; Ersoy, G.; Ozalp, V. C.; Akcali, K. C.; Arica, M. Y.The objective of the present study was to develop 2-hydroxypropyl methacrylate-co-polyethylene methacrylate [p(HPMA-co-PEG-MEMA)] hydrogels that are able to efficiently entrap doxorubicin for the application of loco-regional control of the cancer disease. Systemic chemotherapy provides low clinical benefit while localized chemotherapy might provide a therapeutic advantage. In this study, effects of hydrogel properties such as PEG chains length, cross-linking density, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. In addition, the characterization of the hydrogel formulations was conducted with swelling experiments, permeability tests, Fourier transform infrared, SEM, and contact angle studies. In these drug-hydrogel systems, doxorubicin contains amine group that can be expected a strong Lewis acid-base interaction between drug and polar groups of PEG chains, thus the drug was released in a timely fashion with an electrostatic interaction mechanism. It was observed that doxorubicin release from the hydrogel formulations decreased when the density of cross-linking, and drug/polymer ratio were increased while an increase in the PEG chains length of the macro-monomer (i.e. PEG-MEMA) in the hydrogel system was associated with an increase in water content and doxorubicin release. The biocompatibility of the hydrogel formulations has been investigated using two measures: cytotoxicity test (using lactate dehydrogenase assay) and major serum proteins adsorption studies. Antitumor activity of the released doxorubicin was assessed using a human SNU398 human hepatocellular carcinoma cell line. It was observed that doxorubicin released from all of our hydrogel formulations which remained biologically active and had the capability to kill the tested cancer cells.Item Embargo Modifying NiTi shape memory alloys to reduce nickel ions release through ethylenediamine plasma polymerization for biomedical applications(Elsevier BV, 2024-04) Durukan, Barkan Kagan; Sağdıc, Kutay; Kockar, Benat; İnci, FatihShape memory alloys (SMAs)—a type of smart materials— offer unique benefits for constructing unique medical implants, especially for heart stents, vertebral nails, and braces. One of the widespread SMAs is nitinol (NiTi) which exhibits extraordinary shape memory ability to recover its initial form. However, due to the result of nickel $(Ni^2)$ ions release, long-term usage of NiTi alloys would pose allergic and carcinogenic risks in orthopedics and clinical applications. To tackle these hurdles, we here demonstrate a surface modification technique via plasma polymerization in order to minimize $Ni^2$ ions release. NiTi substrates were initially exploited by plasma polymerization of ethylenediamine (EDA) with varying power values (25–50–75-100 W) and time rates (5–10-15 min) in order to assess the most efficient parameters for minimal toxic metal release. The samples were then tested for 14 days in a biomimicked media. As a result, 75 W-10 min plasma polymerized sample reduced $Ni^2$ ions release by 57.18 % compared to the base specimen. These results offer a significant outcome in deploying NiTi alloys into the biomedical field more safely through surface modifications using the plasma polymerization technique.Item Open Access Porphyrin cross-linked conjugated polymer nanoparticles-based photosensitizer for antimicrobial and anticancer photodynamic therapies(John Wiley & Sons, Inc., 2021-09-27) Duah, Ishmeal Kwaku; Khaligh, Aisan; Koç, Ahmet; Akolpoğlu Başaran, Duygu Deniz; Tuncel, DönüşWe report here the synthesis and characterization of a water dispersible conjugated polymer nanoparticle-based photosensitizer and its application in the antibacterial and anticancer phototherapies. Nanoparticles (CPPN) were synthesized in one-pot by nanoprecipitation method, in which a hydrophobic azide functionalized, red-emitting thiophene-benzothiodiazole based conjugated polymer (CP-AZ) was cross-linked with a hydrophilic, propargylamine functionalized porphyrin (TPP-4AL) through cucurbit[6]uril (CB6) catalyzed azide-alkyne cycloaddition (CB6-AAC) reaction. CPPN demonstrated high stability in aqueous medium for more than a month without any visible aggregation and appeared to be a good photosensitizer with high light-triggered reactive oxygen species (ROS) generation ability. Consequently, CPPN displayed photo-induced biocidal activity against Gram-negative (Escherichia coli, E. coli) and Gram-positive (Bacillus subtilis, B. subtilis and Staphylococcus aureus, S. aureus) bacteria. When bacteria suspension was incubated with CPPN (20 μg ml−1) and irradiated with white light (22 mW cm−2) for 10 min, more than 3.5-log reduction in colony-forming units (CFUs) was recorded for the three model bacteria. CPPN demonstrated minimal dark cytotoxicity against the bacteria. Moreover, the cytotoxicity of CPPN on mammalian cell was studied using MCF-7 breast cancer cell line. The results demonstrated that CPPN is non-toxic to mammalian cells in the dark even at a high concentration of 112.5 μg ml−1 and this feature makes CPPN an ideal photosensitizer.Item Open Access Protein-releasing conductive anodized alumina membranes for nerve-interface materials(Elsevier Ltd, 2016) Altuntas, S.; Buyukserin, F.; Haider, A.; Altinok, B.; Bıyıklı, Necmi; Aslim, B.Nanoporous anodized alumina membranes (AAMs) have numerous biomedical applications spanning from biosensors to controlled drug delivery and implant coatings. Although the use of AAM as an alternative bone implant surface has been successful, its potential as a neural implant coating remains unclear. Here, we introduce conductive and nerve growth factor-releasing AAM substrates that not only provide the native nanoporous morphology for cell adhesion, but also induce neural differentiation. We recently reported the fabrication of such conductive membranes by coating AAMs with a thin C layer. In this study, we investigated the influence of electrical stimulus, surface topography, and chemistry on cell adhesion, neurite extension, and density by using PC 12 pheochromocytoma cells in a custom-made glass microwell setup. The conductive AAMs showed enhanced neurite extension and generation with the electrical stimulus, but cell adhesion on these substrates was poorer compared to the naked AAMs. The latter nanoporous material presents chemical and topographical features for superior neuronal cell adhesion, but, more importantly, when loaded with nerve growth factor, it can provide neurite extension similar to an electrically stimulated CAAM counterpart.Item Open Access Recent advances in bioactive 1D and 2D carbon nanomaterials for biomedical applications(Elsevier, 2018) Erol, Özlem; Uyan, İdil; Hatip, Meyem; Yılmaz, Canelif; Tekinay, Ayse B.; Güler, Mustafa O.One-dimensional (1D) carbon nanotubes (CNTs) and the two-dimensional (2D) graphene represent the most widely studied allotropes of carbon. Due to their unique structural, electrical, mechanical and optical properties, 1D and 2D carbon nanostructures are considered to be leading candidates for numerous applications in biomedical fields, including tissue engineering, drug delivery, bioimaging and biosensors. The biocompatibility and toxicity issues associated with these nanostructures have been a critical impediment for their use in biomedical applications. In this review, we present an overview of the various materials types, properties, functionalization strategies and characterization methods of 1D and 2D carbon nanomaterials and their derivatives in terms of their biomedical applications. In addition, we discuss various factors and mechanisms affecting their toxicity and biocompatibility.Item Open Access Spiral microfluidics device for continuous flow PCR(ASME, 2013) Salemmilani, Reza; Çetin, BarbarosPolymerase-chain-Reaction (PCR) is a thermal cycling (repeated heating and cooling of PCR solution) process for DNA amplification. PCR is the key ingredient in many biomedical applications. One key feature for the success of the PCR is to control the temperature of the solution precisely at the desired temperature levels required for the PCR in a cyclic manner. Microfluidics offers a great advantage over conventional techniques since minute amounts of PCR solution can be heated and cooled with a high rate in a controlled manner. In this study, a microfluidic platform has been proposed for continuous-flow PCR. The microfluidic device consists of a spiral channel on a glass wafer with integrated chromium microheaters. Sub-micron thick microheaters are deposited beneath the micro-channels to facilitate localized heating. The microfluidic device is modeled using COMSOL MultiphysicsR . The fabrication procedure of the device is also discussed and future research directions are addressed. With its compact design, the proposed system can easily be coupled with an integrated microfluidic device to be used in biomedical applications. Copyright © 2013 by ASME.