Browsing by Subject "Tissue engineering"
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Item Open Access Capturing the dynamic scaffold properties of hybrid GelMA based microgels toward tissue engineering and organ-on-chips(2024-09) Çınar, Aslı GizemMicrogels have emerged as versatile materials in tissue engineering, drug delivery, and organ-on-chip (OoC) platforms due to their small scale, uniformity, and customizable properties. Their adaptability as injectable materials and dynamic scaffolds makes them promising candidates for a wide range of biomedical applications. However, traditional methods for characterizing their physical and mechanical behaviors, designed for bulk hydrogels, do not capture the unique properties of microgels, which differ significantly in terms of size and surface-to-volume ratio. This work explores the physical properties of Gelatin Methacryloyl (GelMA)-based Collagen and Hyaluronic Acid Methacrylate (HAMA) hybrid microgels produced via droplet microfluidics, employing novel assays tailored specifically to their micro-scale. Real-time observation of their swelling and degradation properties is carried out using a custom-made platform enabling the tracking of individual microgels, and electron microscopy provides insights into their internal structures, revealing previously unobserved behaviors. We have shown the interpenetrating network formation when GelMA and Collagen are used; and copolymer formation when GelMA and HAMA are used. Under the effect of Collagenase and Hyaluronidase, the individual microgels showed different degradation mechanisms, which have proven to be affected by crosslink densities, enzyme-substrate specificity, enzyme saturation, and properties of the individual network components. The work is extended by focusing more on the temporal profiling of GelMA and HAMA hybrid microgels' behaviors under enzymatic degradation, examining how volume, mechanical properties, and surface features evolve over time, simulating the dynamic conditions encountered in vivo during especially tissue engineering applications. We found that instead of carrying out separate assays to understand the changes, a more holistic approach to evaluating the aforementioned properties gives a more thorough discussion. This approach revealed that changing the ratios of GelMA against HAMA affects the crosslink densities, network formation, and ultimately degrative behaviors. We have observed, for the first time in droplet microfluidics, that a certain combination of GelMA HAMA results in microgels with a network gradient, getting denser towards the center, while the other combinations only increased the crosslink densities without altering the porous homogeneity. Furthermore, the number of microgels exposed to the same concentration of enzyme is altered to emulate different injection volumes into similar tissues, or the enzyme concentration is altered to emulate injection into different tissues. These assays showed the sensitivity of degradation profiles against enzyme saturation and competition. Meanwhile, the stiffness and surface morphology changes of microgels during degradation are examined, revealing the importance of network homogeneity in presenting stable mechanical properties during degradation. Lastly, drug release from these scaffolds is modeled for prospective applications, and their relation to scaffold properties is evaluated. Overall, this thesis is poised to discover the peculiar behaviors of GelMA hybrid microgels produced with droplet microfluidics uncovering the importance of carrying out investigations true to the sample at hand and the conditions that will be imposed upon them during application.Item Open Access Chemical and topographical modification of PHBV surface to promote osteoblast alignment and confinement(John Wiley & Sons, Inc., 2008) Kenar, H.; Kocabas, A.; Aydınlı, Atilla; Hasirci, V.Proper cell attachment and distribution, and thus stronger association in vivo between a bone implant and native tissue will improve the success of the implant. In this study, the aim was to achieve promotion of attachment and uniform distribution of rat mesenchymal stem cell-derived osteoblasts by introducing chemical and topographical cues on poly(3-hydroxybutyrate-co-3- hydroxyvalerate) (PHBV) film surfaces. As the chemical cues, either alkaline phosphatase was covalently immobilized on the film surface to induce deposition of calcium phosphate minerals or fibrinogen was adsorbed to improve cell adhesion. Microgrooves and micropits were introduced on the film surface by negative replication of micropatterned Si wafers. Both chemical cues improved cell attachment and even distribution on the PHBV films, but Fb was more effective especially when combined with the micropatterns. Cell alignment (<10° deviation angle) parallel to chemically modified microgrooves (1, 3, or 8 μm groove width) and on 10 μm-thick Fb lines printed on the unpatterned films was achieved. The cells on unpatterned and 5 μm-deep micropitted films were distributed and oriented randomly. Results of this study proved that microtopographies on PHBV can improve osseointegration when combined with chemical cues, and that microgrooves and cell adhesive protein lines on PHBV can guide selective osteoblast adhesion and alignment.Item Open Access Contact guidance enhances the quality of a tissue engineered corneal stroma(John Wiley & Sons, Inc., 2008) Vrana, E.; Builles, N.; Hindie, M.; Damour O.; Aydınlı, Atilla; Hasirci, V.Corneal stroma is a very complex structure, composed of 200 lamellae of oriented collagen fibers. This highly complex nature of cornea is known to be important for its transparency and mechanical integrity. Thus, an artificial cornea design has to take into account this complex structure. In this study, behavior of human corneal keratocytes on collagen films patterned with parallel channels was investigated. Keratocytes proliferated well on films and reached confluency after 7 days in the incubation medium. Nearly all of the cells responded to the patterns and were aligned in contrast to the cells on unpatterned surfaces. Collagen type I and keratan sulfate secreted by keratocytes on patterned films appeared to be aligned in the direction of the patterns. The films showed an intermediate degradation over the course of a month. On the whole, transparency of the films increased with degradation and decreased by the presence of the cells. The decrease was, however, low and transparency level was maintained on the patterned films while on the unpatterned films a sharp decrease in transparency was followed by an improvement. This was due to the more organized distribution of cells and the oriented secretion of extracellular matrix molecules on patterned collagen films. Thus, these results suggest that application of contact guidance in cornea tissue engineering may facilitate the remodeling process, hence decrease the rehabilitation period.Item Open Access Cornea engineering on polyester carriers(John Wiley & Sons, Inc., 2006) Zorlutuna, P.; Tezcaner, A.; Kiyat, I.; Aydınlı, Atilla; Hasirci, V.In this study, biodegradable polyester based carriers were designed for tissue engineering of the epithelial and the stromal layers of the cornea, and the final construct was tested in vitro. In the construction of the epithelial layer, micropatterned films were prepared from blends of biodegradable and biocompatible polyesters of natural (PHBV) and synthetic (P(L/DL)LA) origin, and these films were seeded with D407 (retinal pigment epithelial) cells. To improve cell adhesion and growth, the films were coated with fibronectin. To serve as the stromal layer of the cornea, highly porous foams of P(L/DL)LA-PHBV blends were seeded with 3T3 fibroblasts. Cell numbers on the polyester carriers were significantly higher than those on the tissue culture polystyrene control. The cells and the carriers were characterized scanning electron micrographs showed that the foam was highly porous and the pores were interconnected. 3T3 Fibroblasts were distributed quite homogeneously at the seeding site, but probably because of the high thickness of the carrier (∼6 mm); they could not sufficiently populate the core (central parts of the foam) during the test duration. The D407 cells formed multilayers on the micropatterned polyester film. Immunohistochemical studies showed that the cells retained their phenotype during culturing; D407 cells formed tight junctions characteristic of epithelial cells, and 3T3 cells deposited collagen type I into the foams. On the basis of these results, we concluded that the micropatterned films and the foams made of P(L/DL)LA-PHBV blends have a serious potential as tissue engineering carriers for the reconstruction of the epithelial and stromal layers of the cornea.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 Drug delivery system based on cyclodextrin-naproxen inclusion complex incorporated in electrospun polycaprolactone nanofibers(Elsevier, 2014) Canbolat, M. F.; Celebioglu A.; Uyar, TamerIn this study, we select naproxen (NAP) as a reference drug and electrospun poly (e-caprolactone) (PCL) nanofibers as a fibrous matrix for our drug-delivery system. NAP was complexed with beta-cyclodextrin (βCD) to form inclusion complex (NAP-βCD-IC) and then NAP-βCD-IC was incorporated into PCL nanofibers via electrospinning. The incorporation of NAP without CD-IC into electrospun PCL was also carried out for a comparative study. Our aim is to analyze the release profiles of NAP from PCL/NAP and PCL/NAP-βCD-IC nanofibers and we investigate the effect of CD-IC on the release behavior of NAP from the nanofibrous PCL matrix. The characterization of NAP-βCD-IC and the presence of CD-IC in PCL/NAP-βCD-IC nanofibers were studied by FTIR, XRD, TGA, NMR and SEM. The SEM imaging of the electrospun PCL/NAP and PCL/NAP-βCD-IC nanofibers reveal that the average fiber diameter of these nanofibers is around 300. nm, in addition, the aggregates of CD-IC in PCL/NAP-βCD-IC nanofibers is observed. The release study of NAP in buffer solution elucidate that the PCL/NAP-βCD-IC nanofibers have higher release amount of NAP than the PCL/NAP nanofibers due to the solubility enhancement of NAP by CD-IC.Item Open Access Electrostatic effects on nanofiber formation of self-assembling peptide amphiphiles(Elsevier, 2011) Toksoz, S.; Mammadov R.; Tekinay, A. B.; Güler, Mustafa O.Self-assembling peptide amphiphile molecules have been of interest to various tissue engineering studies. These molecules self-assemble into nanofibers which organize into three-dimensional networks to form hydrocolloid systems mimicking the extracellular matrix. The formation of nanofibers is affected by the electrostatic interactions among the peptides. In this work, we studied the effect of charged groups on the peptides on nanofiber formation. The self-assembly process was studied by pH and zeta potential measurements, FT-IR, circular dichroism, rheology, atomic force microscopy, scanning electron microscopy and transmission electron microscopy. The aggregation of the peptides was triggered upon neutralization of the charged residues by pH change or addition of electrolyte or biomacromolecules. Understanding the controlled formation of the hydrocolloid gels composed of peptide amphiphile nanofibers can lead us to develop in situ gel forming bioactive collagen mimetic nanofibers for various tissue engineering studies including bioactive surface coatings. © 2010 Elsevier Inc.Item Open Access Glycosaminoglycan-Mimetic Signals Direct the Osteo/Chondrogenic Differentiation of Mesenchymal Stem Cells in a Three-Dimensional Peptide Nanofiber Extracellular Matrix Mimetic Environment(American Chemical Society, 2016-02) Arslan, E.; Güler, Mustafa O.; Tekinay, A. B.Recent efforts in bioactive scaffold development focus strongly on the elucidation of complex cellular responses through the use of synthetic systems. Designing synthetic extracellular matrix (ECM) materials must be based on understanding of cellular behaviors upon interaction with natural and artificial scaffolds. Hence, due to their ability to mimic both the biochemical and mechanical properties of the native tissue environment, supramolecular assemblies of bioactive peptide nanostructures are especially promising for development of bioactive ECM-mimetic scaffolds. In this study, we used glycosaminoglycan (GAG) mimetic peptide nanofiber gel as a three-dimensional (3D) platform to investigate how cell lineage commitment is altered by external factors. We observed that amount of fetal bovine serum (FBS) presented in the cell media had synergistic effects on the ability of GAG-mimetic nanofiber gel to mediate the differentiation of mesenchymal stem cells into osteogenic and chondrogenic lineages. In particular, lower FBS concentration in the culture medium was observed to enhance osteogenic differentiation while higher amount FBS promotes chondrogenic differentiation in tandem with the effects of the GAG-mimetic 3D peptide nanofiber network, even in the absence of externally administered growth factors. We therefore demonstrate that mesenchymal stem cell differentiation can be specifically controlled by the combined influence of growth medium components and a 3D peptide nanofiber environment.Item Open Access Graph walks for classification of histopathological images(IEEE, 2013) Olgun, Gülden; Sokmensuer, C.; Gündüz-Demir, ÇiğdemThis paper reports a new structural approach for automated classification of histopathological tissue images. It has two main contributions: First, unlike previous structural approaches that use a single graph for representing a tissue image, it proposes to obtain a set of subgraphs through graph walking and use these subgraphs in representing the image. Second, it proposes to characterize subgraphs by directly using distribution of their edges, instead of employing conventional global graph features, and use these characterizations in classification. Our experiments on colon tissue images reveal that the proposed structural approach is effective to obtain high accuracies in tissue image classification. © 2013 IEEE.Item Open Access Macroporous Surgical Mesh from a Natural Cocoon Composite(2022-04-25) Chen, Y.-M.; Zang, L.-S.; Koc-Bilican, B.; Bilican, Ismail; Holland, C.; Cansaran-Duman, D.; Karaduman, T.; Çolak, A.; Bayır, Y.; Halici, Z.; Ozmen, S.; Ali, A.; Labidi, J.; Elbuken, Caglar; Kaya, M.Recently, traditional polymer-based surgical meshes have drawn unwanted attention as a result of host tissue complications arising from infection, biocompatibility, and mechanical compatibility. Seeking an alternative solution, we present a hierarchically structured nanofibrous surgical mesh derived from the naturally woven cocoon of the Japanese giant silkworm, termed MothMesh. We report that it displays nontoxicity, biocompatibility, suitable mechanical properties, and porosity while showing no adverse effect in animal trials and even appears to enhance cell proliferation. Hence, we assert that the use of this natural material may provide an effective and improved alternative to existing synthetic meshesItem Open Access Nanoengineering hybrid supramolecular multilayered biomaterials using polysaccharides and self-assembling peptide amphiphiles(Wiley-VCH Verlag, 2017) Borges, J.; Sousa, M. P.; Cinar, G.; Caridade, S. G.; Güler, Mustafa O.; Mano, J. F.Developing complex supramolecular biomaterials through highly dynamic and reversible noncovalent interactions has attracted great attention from the scientific community aiming key biomedical and biotechnological applications, including tissue engineering, regenerative medicine, or drug delivery. In this study, the authors report the fabrication of hybrid supramolecular multilayered biomaterials, comprising high-molecular-weight biopolymers and oppositely charged low-molecular-weight peptide amphiphiles (PAs), through combination of self-assembly and electrostatically driven layer-by-layer (LbL) assembly approach. Alginate, an anionic polysaccharide, is used to trigger the self-assembling capability of positively charged PA and formation of 1D nanofiber networks. The LbL technology is further used to fabricate supramolecular multilayered biomaterials by repeating the alternate deposition of both molecules. The fabrication process is monitored by quartz crystal microbalance, revealing that both materials can be successfully combined to conceive stable supramolecular systems. The morphological properties of the systems are studied by advanced microscopy techniques, revealing the nanostructured dimensions and 1D nanofibrous network of the assembly formed by the two molecules. Enhanced C2C12 cell adhesion, proliferation, and differentiation are observed on nanostructures having PA as outermost layer. Such supramolecular biomaterials demonstrate to be innovative matrices for cell culture and hold great potential to be used in the near future as promising biomimetic supramolecular nanoplatforms for practical applications.Item Open Access One-Step Fabrication of Biocompatible Multifaceted Nanocomposite Gels and Nanolayers(American Chemical Society, 2017) Topuz, F.; Bartneck, M.; Pan, Y.; Tacke, F.Nanocomposite gels are a fascinating class of polymeric materials with an integrative assembly of organic molecules and organic/inorganic nanoparticles, offering a unique hybrid network with synergistic properties. The mechanical properties of such networks are similar to those of natural tissues, which make them ideal biomaterial candidates for tissue engineering applications. Existing nanocomposite gel systems, however, lack many desirable gel properties, and their suitability for surface coatings is often limited. To address this issue, this article aims at generating multifunctional nanocomposite gels that are injectable with an appropriate time window, functional with bicyclononynes (BCN), biocompatible and slowly degradable, and possess high mechanical strength. Further, the in situ network-forming property of the proposed system allows the fabrication of ultrathin nanocomposite coatings in the submicrometer range with tunable wettability and roughness. Multifunctional nanocomposite gels were fabricated under cytocompatible conditions (pH 7.4 and T = 37 °C) using laponite clays, isocyanate (NCO)-terminated sP(EO-stat-PO) macromers, and clickable BCN. Several characterization techniques were employed to elucidate the structure-property relationships of the gels. Even though the NCO-sP(EO-stat-PO) macromers could form a hydrogel network in situ on contact with water, the incorporation of laponite led to significant improvement of the mechanical properties. BCN motifs with carbamate links were used for a metal-free click ligation with azide-functional molecules, and the subsequent gradual release of the tethered molecules through the hydrolysis of carbamate bonds was shown. The biocompatibility of the hydrogels was examined through murine macrophages, showing that the material composition strongly affects cell behavior.Item Open Access Peptide-based bioinspired functional materials(2016-12) Şentürk, Oya İlkeAbility of nature to build complex systems via step-by-step addition of small building blocks with distinctive qualities and multi-functionalities has garnered massive attention which gave a rise to biomimetic or biologically inspired synthesis concept. Biomimetic synthesis mimics nature’s approach and design principles offering various combinations of new concepts and designs to adapt them in synthetic materials or processes.[1] Up to date, many efforts have been made to mimic nature’s approach for the development and fabrication of more effective synthetic systems and structures to compensate drawbacks and overcome reported challenges in existing models.[2] In the first part of this thesis, development of a bioinspired, heterogeneous and recyclable Cu-complex catalyst for [3+2] Huisgen cycloaddition reaction, also known as click reaction, is described. A copper binding peptide sequence, human tripeptide Gly-His-Lys (GHK), is utilized for such purpose.[3] GHK sequence is linked with an alkyl tail comprising 6, GHK-6-abx, or 11, GHK-11-adx, carbons to the polystyrene ring amide resin where it is used as a solid support and complexed with Cu(II). The catalyst provides better catalytic activities in aqueous solvent rather than organic solvents which is a desirable property for green chemistry point of view. Accordingly, an enzyme-like catalyst is described where alkyl tail offers hydrophobic regions for organic reagents to be immobilized closer to the Cu(II), catalytic site of the molecule, and increases reaction yields. 80% yield can be obtained from GHK-11-adx-Cu complex catalyst in water using Cu(II) loadings as low as 0.5 mol% and catalytic activity can be retained up to three cycles of reactions. In the second study of this thesis, we developed a versatile system to induce self-assembly of peptide amphiphiles by using light which is a readily available and cheap reagent allowing precise stimulation and providing quick response. For this purpose, a photo-labile calcium chelator, Nitr-T, which releases free Ca2+ ions upon irradiation is mixed with a negatively charged E2-PA. E2-PA, a negatively charged PA molecule, self-assembles to form a hydrogel in the presence of free Ca2+ ions provided by the NitrT-Ca2+ complex, and goes back to its solution state when free Ca2+ ions are removed from the medium by the addition of EDTA solution. Consequently, swelling characteristics and mechanical properties of any negatively charged Peptide-Amphiphile (PA) can be controlled by using light as stimuli by simply mixing PA solution with NitrT-Ca2+ complex without any further modification or covalent modification in the molecule’s structure. In overall, peptide-based, bioinspired functional materials for various applications like catalysts and tissue engineering was reported in the scope of this thesis. Peptides and peptide-amphiphiles present a very useful member in number of biomimetic applications as they are indispensable part of many biological processes capable of performing very complicated tasks.Item Open Access Preparation and characterization of poly(hydroxyethyl methacrylate-co-poly(ethyleneglycol-methacrylate)/hydroxypropyl-chitosan) hydrogel films: Adhesion of rat mesenchymal stem cells(Hangug Gobunja Haghoi, 2010-12-02) Bayramoglu, G.; Akcalı, K. C.; Gultekin, S.; Bengu, E.; Arica, M. Y.This study examined the effects of the surface properties of the materials, such as the hydroxyl, methyl and amino groups, on rat bone marrow derived Mesenchymal Stem Cell (MSC) seeding. A series of hydrogels were prepared in film form using 2-hydroxyethyl methacrylate (pHEMA), poly(ethyleneglycol) methacrylate (PEG-MA), and/or hydroxypropyl-chitosan (HPC). The physicochemical properties of these hydrogel films, such as water content, functional groups, contact angle, surface energy and thermal properties were affected by the composition of the materials. The ability of the MSCs to form colonies, as well as their viability on these materials were also analyzed. The water content of the hydrogel films increased with increasing PEG-MA and HPC ratio in the hydrogel. Contact angle measurements of the surface of the hydrogel films demonstrated that all the materials gave rise to a significantly hydrophilic surface compared to pure pHEMA. The blood protein interactions and platelet adhesion were reduced significantly on the surface of the materials upon the incorporation of PEG-MA compared to the control pure pHEMA and vice versa for HPC. The ability of the MSCs to adhere and form colonies on these materials was also analyzed. The results showed that these materials are suitable candidates to isolate and expand MSCs.Item Open Access Self-assembled proteins and peptides as scaffolds for tissue regeneration(Wiley-VCH Verlag, 2015) Loo, Y.; Goktas, M.; Tekinay, A. B.; Güler, Mustafa O.; Hauser, C. A. E.; Mitraki, A.Self-assembling proteins and peptides are increasingly gaining interest for potential use as scaffolds in tissue engineering applications. They self-organize from basic building blocks under mild conditions into supramolecular structures, mimicking the native extracellular matrix. Their properties can be easily tuned through changes at the sequence level. Moreover, they can be produced in sufficient quantities with chemical synthesis or recombinant technologies to allow them to address homogeneity and standardization issues required for applications. Here. recent advances in self-assembling proteins, peptides, and peptide amphiphiles that form scaffolds suitable for tissue engineering are reviewed. The focus is on a variety of motifs, ranging from minimalistic dipeptides, simplistic ultrashort aliphatic peptides, and peptide amphiphiles to large "recombinamer" proteins. Special emphasis is placed on the rational design of self-assembling motifs and biofunctionalization strategies to influence cell behavior and modulate scaffold stability. Perspectives for combination of these "bottom-up" designer strategies with traditional "top-down" biofabrication techniques for new generations of tissue engineering scaffolds are highlighted. Recent advances in self-assembling proteins, peptides, and peptide amphiphiles that form scaffolds suitable for tissue engineering are discussed. Rational design and biofunctionalization strategies for a variety of motifs ranging from minimalistic dipeptides, ultrashort aliphatic peptides, and peptide amphiphiles to large "recombinamer" proteins are reviewed and challenges and perspectives for their widespread adoption in applications are highlighted.Item Open Access Spatial organization of functional groups on bioactive supramolecular glycopeptide nanofibers for differentiation of mesenchymal stem cells (MSCs) to brown adipogenesis(American Chemical Society, 2016-12) Caliskan, O. S.; Sardan, Ekiz M.; Tekinay, A. B.; Güler, Mustafa O.Spatial organization of bioactive moieties in biological materials has significant impact on the function and efficiency of these systems. Here, we demonstrate the effect of spatial organization of functional groups including carboxylate, amine, and glucose functionalities by using self-assembled peptide amphiphile (PA) nanofibers as a bioactive scaffold. We show that presentation of bioactive groups on glycopeptide nanofibers affects mesenchymal stem cells (MSCs) in a distinct manner by means of adhesion, proliferation, and differentiation. Strikingly, when the glutamic acid is present in the glycopeptide backbone, the PA nanofibers specifically induced differentiation of MSCs into brown adipocytes in the absence of any differentiation medium as shown by lipid droplet accumulation and adipogenic gene marker expression analyses. This effect was not evident in the other glycopeptide nanofibers, which displayed the same functional groups but with different spatial organization. Brown adipocytes are attractive targets for obesity treatment and are found in trace amounts in adults, which also makes this specific glycopeptide nanofiber system an attractive tool to study molecular pathways of brown adipocyte formation.Item Open Access Surface-modified bacterial nanofibrillar PHB scaffolds for bladder tissue repair(Taylor and Francis Ltd., 2016) Karahaliloǧlu, Z.; Demirbilek, M.; Şam, M.; Saǧlam, N.; Mizrak, A. K.; Denkbaş, E. B.The aim of the study is in vitro investigation of the feasibility of surface-modified bacterial nanofibrous poly [(R)-3-hydroxybutyrate] (PHB) graft for bladder reconstruction. In this study, the surface of electrospun bacterial PHB was modified with PEG- or EDA via radio frequency glow discharge method. After plasma modification, contact angle of EDA-modified PHB scaffolds decreased from 110 � 1.50 to 23 � 0.5 degree. Interestingly, less calcium oxalate stone deposition was observed on modified PHB scaffolds compared to that of non-modified group. Results of this study show that surface-modified scaffolds not only inhibited calcium oxalate growth but also enhanced the uroepithelial cell viability and proliferation.Item Open Access Therapeutic nanomaterials for cartilage regeneration(John Wiley & Sons, 2016-03-11) Arslan, Elif; Üstün Yaylacı, Seher; Güler, Mustafa O.; Tekinay, Ayşe B.; Güler, Mustafa O.; Tekinay, Ayşe B.Articular cartilage (AC) is the main focus of this chapter and indeed most cartilage regeneration studies, since it is commonly affected by diseases and traumatic injuries that necessitate its therapeutic regeneration. There are four main approaches for cartilage regeneration: cultured cell implantation, engineered tissue construct implantation, scaffoldless tissue regeneration, and guided tissue regeneration. Cartilage growth, development, and repair are dependent on both biomechanical and biological signals. The most important growth factors used in cartilage regeneration and tissue engineering approaches are the transforming growth factor ß (TGF‐ß) family members, particularly TGF‐ß1 and TGF‐ß3. Overall, new strategies in the field of cartilage regeneration focus on the unique biochemical and physical properties of native cartilage to design novel tissue constructs that are decorated with cartilage‐specific signals and display suitable anatomical geometries and mechanical properties for the treatment of large tissue defects.Item Open Access Two-tier tissue decomposition for histopathological image representation and classification(Institute of Electrical and Electronics Engineers, 2015) Gultekin, T.; Koyuncu, C. F.; Sokmensuer, C.; Gunduz Demir, C.In digital pathology, devising effective image representations is crucial to design robust automated diagnosis systems. To this end, many studies have proposed to develop object-based representations, instead of directly using image pixels, since a histopathological image may contain a considerable amount of noise typically at the pixel-level. These previous studies mostly employ color information to define their objects, which approximately represent histological tissue components in an image, and then use the spatial distribution of these objects for image representation and classification. Thus, object definition has a direct effect on the way of representing the image, which in turn affects classification accuracies. In this paper, our aim is to design a classification system for histopathological images. Towards this end, we present a new model for effective representation of these images that will be used by the classification system. The contributions of this model are twofold. First, it introduces a new two-tier tissue decomposition method for defining a set of multityped objects in an image. Different than the previous studies, these objects are defined combining texture, shape, and size information and they may correspond to individual histological tissue components as well as local tissue subregions of different characteristics. As its second contribution, it defines a new metric, which we call dominant blob scale, to characterize the shape and size of an object with a single scalar value. Our experiments on colon tissue images reveal that this new object definition and characterization provides distinguishing representation of normal and cancerous histopathological images, which is effective to obtain more accurate classification results compared to its counterparts.