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    Publication
    (Bis)phosphonic acid-functionalized poly(ethyleneimine)- poly(amido amine)s for selective in vitro transfection of osteosarcoma cells
    (Amer Chemical Soc, 2021) Güven, Melek Naz; Altuncu, Seçkin; Konca, Yeliz Utku; Avcı, Duygu; N/A; Department of Chemistry; Demirci, Gözde; Acar, Havva Funda Yağcı; Master Student; Faculty Member; Department of Chemistry; Graduate School of Sciences and Engineering; College of Sciences; N/A; 178902
    Osteosarcoma is aggressive bone cancer, whose treatment has not changed significantly for the past few decades. Although gene therapy methods have emerged as potential treatment routes, the need for efficient and nontoxic gene delivery systems targeting osteosarcoma cells remains a challenge. High-molecular-weight poly(ethyleneimine)s (PEIs) are used as universal transfection agents; however, they cause significant cytotoxicity. on the other hand, poly(amido amine)s (PAAs) are biocompatible, biodegradable polymers with promising transfection efficiency, which should be improved further. In this paper, we combined low-molecular-weight branched PEI (1800 Da) and PAA macromers functionalized with various amounts of (bis)phosphonic acid groups and pentanol (via 5-amino-1-pentanol (AP)). The (bis)phosphonic acid groups on these polymers (PAEIs) are intended to facilitate bone targeting. The molecular weights of the PAEI polymers were between 2600 and 8600 g/mol. Their cytotoxicities and green fluorescence protein (GFP) transfection efficiencies were tested on an osteosarcoma cell line (U-2 OS cells), which is challenging to transfect, and healthy muscle cells (C2C12). Both the cytotoxicity and transfection efficiency of PAEIs were affected by the phosphonic acid (via APA, 2-aminoethyl phosphonic acid) or bisphosphonic acid (via ALE, sodium alendronate) content of the polymers. PAEIs are more cytocompatible than both linear and branched 25 kDa PEI. ALE-containing PAEIs provided better transfection than APA-containing ones. The most efficient PAEI polymer, containing a 0.7:0.3 AP/ALE ratio, displayed a transfection efficiency that was five times higher than that of 25 kDa PEI with dramatically better cytocompatibility. This is comparable to FuGENE, but PAEI is more advantageous in selective transfection of the U-2 OS. This set of polymers may be promising candidates for targeted gene therapy of osteosarcoma.
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    PublicationOpen Access
    3D bioprinted organ?on?chips
    (Wiley, 2022) Mustafaoğlu, Nur; Zhang, Yu Shrike; Department of Mechanical Engineering; N/A; N/A; Dabbagh, Sajjad Rahmani; Sarabi, Misagh Rezapour; Birtek, Mehmet Tuğrul; Taşoğlu, Savaş; Faculty Member; Department of Mechanical Engineering; KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); College of Engineering; Graduate School of Social Sciences and Humanities; Graduate School of Sciences and Engineering; N/A; N/A; N/A; 291971
    Organ-on-a-chip (OOC) platforms recapitulate human in vivo-like conditions more realistically compared to many animal models and conventional two-dimensional cell cultures. OOC setups benefit from continuous perfusion of cell cultures through microfluidic channels, which promotes cell viability and activities. Moreover, microfluidic chips allow the integration of biosensors for real-time monitoring and analysis of cell interactions and responses to administered drugs. Three-dimensional (3D) bioprinting enables the fabrication of multicell OOC platforms with sophisticated 3D structures that more closely mimic human tissues. 3D-bioprinted OOC platforms are promising tools for understanding the functions of organs, disruptive influences of diseases on organ functionality, and screening the efficacy as well as toxicity of drugs on organs. Here, common 3D bioprinting techniques, advantages, and limitations of each method are reviewed. Additionally, recent advances, applications, and potentials of 3D-bioprinted OOC platforms for emulating various human organs are presented. Last, current challenges and future perspectives of OOC platforms are discussed.
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    3D coffee stains
    (Royal Soc Chemistry, 2017) N/A; N/A; Department of Electrical and Electronics Engineering; N/A; N/A; N/A; Department of Molecular Biology and Genetics; Department of Chemistry; Department of Chemistry; Department of Electrical and Electronics Engineering; Doğru-Yüksel, Itır Bakış; Söz, Çağla Koşak; Press, Daniel Aaron; Melikov, Rustamzhon; Begar, Efe; Çonkar, Deniz; Karalar, Elif Nur Fırat; Yılgör, Emel; Yılgör, İskender; Nizamoğlu, Sedat; PhD Student; PhD Student; Researcher; PhD Student; PhD Student; PhD Student; PhD Student; Faculty Member; Researcher; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemistry; Department of Electrical and Electronics Engineering; N/A; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); N/A; N/A; N/A; N/A; N/A; N/A; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; College of Sciences; College of Engineering; N/A; N/A; N/A; N/A; N/A; N/A; 206349; N/A; 24181; 130295
    When a liquid droplet (e.g., coffee, wine, etc.) is splattered on a surface, the droplet dries in a ring-shaped stain. This widely observed pattern in everyday life occurs due to the phenomenon known as a coffee stain (or coffee ring) effect. While the droplet dries, the capillary flow moves and deposits the particles toward the pinned edges, which shows a 2D ring-like structure. Here we demonstrate the transition from a 2D to a 3D coffee stain that has a well-defined and hollow sphere-like structure, when the substrate surface is switched from hydrophilic to superhydrophobic. The 3D stain formation starts with the evaporation of the pinned aqueous colloidal droplet placed on a superhydrophobic surface that facilitates the particle flow towards the liquid-air interface. This leads to spherical skin formation and a cavity in the droplet. Afterwards the water loss in the cavity due to pervaporation leads to bubble nucleation and growth, until complete evaporation of the solvent. In addition to the superhydrophobicity of the surface, the concentration of the solution also has a significant effect on 3D coffee stain formation. Advantageously, 3D coffee stain formation in a pendant droplet configuration enables the construction of all-protein lasers by integrating silk fibroin with fluorescent proteins. No tools, components and/or human intervention are needed after the construction process is initiated; therefore, 3D coffee-stains hold promise for building self-assembled and functional 3D constructs and devices from colloidal solutions.
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    PublicationOpen Access
    3D engineered neural co-culture model and neurovascular effects of marine fungi-derived citreohybridonol
    (American Institute of Physics (AIP) Publishing, 2022) Polat, İrem; Özkaya, Ferhat Can; El-Neketi, Mona; Ebrahim, Weaam; Şengül, Gülgün; Department of Mechanical Engineering; Sokullu, Emel; Sarabi, Misagh Rezapour; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); School of Medicine; Graduate School of Sciences and Engineering; College of Engineering; 163024; N/A; 291971
    Marine-based biomolecules are emerging metabolites that have gained attention for developing novel biomaterials, drugs, and pharmaceutical in vitro platforms. Here, we developed a 3D engineered neural co-culture model via a 3D prototyped sliding frame-platform for multi-step UV lithography and investigated the neurovascular potential of citreohybridonol in neuroblastoma treatment. Citreohybridonol was isolated from a sponge-derived fungus Penicillium atrovenetum. The model was characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy analysis. Human umbilical cord vein endothelial cells (HUVECs) and neuroblastoma (SH-SY5Y) cell lines were encapsulated in gelatin methacrylate (GelMA) with and without citreohybridonol. The effect of citreohybridonol on the proliferation capacity of cells was assessed via cell viability and immunostaining assays. GelMA and 3D culture characterization indicated that the cells were successfully encapsulated as axenic and mixed with/without citreohybridonol. The cytotoxic test confirmed that the 3D microenvironment was non-toxic for cultural experiments, and it showed the inhibitory effects of citreohybridonol on SH-SY5Y cells and induced the proliferation of HUVECs. Finally, immunohistochemical staining demonstrated that citreohybridonol suppressed SH-SY5Y cells and induced vascularization of HUVECs in mixed 3D cell culture.
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    3D printed biodegradable polyurethaneurea elastomer recapitulates skeletal muscle structure and function
    (American Chemical Society (ACS), 2021) Gokyer, Seyda; Berber, Emine; Vrana, Engin; Orhan, Kaan; Abou Monsef, Yanad; Guvener, Orcun; Zinnuroglu, Murat; Oto, Cagdas; Huri, Pinar Yilgor; Department of Chemistry; Department of Chemistry; Yılgör, Emel; Yılgör, İskender; Researcher; Faculty Member; Department of Chemistry; College of Sciences; College of Sciences; N/A; 24181
    Effective skeletal muscle tissue engineering relies on control over the scaffold architecture for providing muscle cells with the required directionality, together with a mechanical property match with the surrounding tissue. Although recent advances in 3D printing fulfill the first requirement, the available synthetic polymers either are too rigid or show unfavorable surface and degradation profiles for the latter. In addition, natural polymers that are generally used as hydrogels lack the required mechanical stability to withstand the forces exerted during muscle contraction. Therefore, one of the most important challenges in the 3D printing of soft and elastic tissues such as skeletal muscle is the limitation of the availability of elastic, durable, and biodegradable biomaterials. Herein, we have synthesized novel, biocompatible and biodegradable, elastomeric, segmented polyurethane and polyurethaneurea (TPU) copolymers which are amenable for 3D printing and show high elasticity, low modulus, controlled biodegradability, and improved wettability, compared to conventional polycaprolactone (PCL) and PCL-based TPUs. The degradation profile of the 3D printed TPU scaffold was in line with the potential tissue integration and scaffold replacement process. Even though TPU attracts macrophages in 2D configuration, its 3D printed form showed limited activated macrophage adhesion and induced muscle-like structure formation by C2C12 mouse myoblasts in vitro, while resulting in a significant increase in muscle regeneration in vivo in a tibialis anterior defect in a rat model. Effective muscle regeneration was confirmed with immunohistochemical assessment as well as evaluation of electrical activity produced by regenerated muscle by EMG analysis and its force generation via a custom-made force transducer. Micro-CT evaluation also revealed production of more muscle-like structures in the case of implantation of cell-laden 3D printed scaffolds. These results demonstrate that matching the tissue properties for a given application via use of tailor-made polymers can substantially contribute to the regenerative outcomes of 3D printed tissue engineering scaffolds.
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    3D printed poly(lactic acid) scaffolds modified with chitosan and hydroxyapatite for bone repair applications
    (Elsevier, 2020) N/A; N/A; N/A; N/A; Department of Chemistry; Department of Chemical and Biological Engineering; Department of Chemistry; Nazeer, Muhammad Anwaar; Önder, Özgün Can; Sevgili, İlkem; Yılgör, Emel; Kavaklı, İbrahim Halil; Yılgör, İskender; PhD Student; PhD Student; PhD Student; Researcher; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Engineering; College of Sciences; N/A; N/A; N/A; N/A; 40319; 24181
    3D printed poly(lactic acid) (PLA) scaffolds surface modified with chitosan (CS) and hydroxyapatite (HA) to produce a novel bioactive composite scaffold is reported. Excellent mechanical properties of PLA, the bioactivity of CS, and osteogenic characteristics of HA are combined to fabricate composite scaffolds using a simple desktop 3D printer. Scaffolds were characterized through attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD) and water contact angle measurements before and after modification. Formic acid was used as a solvent to prepare stable CS/HA dispersions and was found to be a suitable solvent for producing PLA/CS/HA composites. Surface properties of modified scaffolds were superior in terms of hydrophilicity and bioactivity, which resulted in enhanced attachment and proliferation of human osteosarcoma cells in vitro compared to the unmodified PLA scaffolds.
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    3D printing of cytocompatible gelatin-cellulose-alginate blend hydrogels
    (Wiley-V C H Verlag Gmbh, 2020) Erkoc, Pelin; Uvak, Ileyna; Odeh, Yazan Nitham; Akdogan, Ozan; Odeh, Yazan Nitham; Akdogan, Ozan; N/A; Department of Chemistry; Department of Chemical and Biological Engineering; Nazeer, Muhammad Anwaar; Batool, Syeda Rubab; Kızılel, Seda; PhD Student; Researcher; Faculty Member; Department of Chemistry; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Engineering; N/A; N/A; 28376
    3D bioprinting of hydrogels has gained great attention due to its potential to manufacture intricate and customized scaffolds that provide favored conditions for cell proliferation. Nevertheless, plain natural hydrogels can be easily disintegrated, and their mechanical strengths are usually insufficient for printing process. Hence, composite hydrogels are developed for 3D printing. This study aims to develop a hydrogel ink for extrusion-based 3D printing which is entirely composed of natural polymers, gelatin, alginate, and cellulose. Physicochemical interactions between the components of the intertwined gelatin-cellulose-alginate network are studied via altering copolymer ratios. The structure of the materials and porosity are assessed using infrared spectroscopy, swelling, and degradation experiments. The utility of this approach is examined with two different crosslinking strategies using glutaraldehyde or CaCl2. Multilayer cylindrical structures are successfully 3D printed, and their porous structure is confirmed by scanning electron microscopy and Brunauer-Emmett-Teller surface area analyses. Moreover, cytocompatibility of the hydrogel scaffolds is confirmed on fibroblast cells. The developed material is completely natural, biocompatible, economical, and the method is facile. Thus, this study is important for the development of advanced functional 3D hydrogels that have considerable potential for biomedical devices and artificial tissues.
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    PublicationOpen Access
    3D printing of elastomeric bioinspired complex adhesive microstructures
    (Wiley, 2021) Dayan, Cem Balda; Chun, Sungwoo; Krishna Subbaiah, Nagaraj; Drotlef, Dirk Michael; Akolpoğlu, Mükrime Birgül; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104
    Bioinspired elastomeric structural adhesives can provide reversible and controllable adhesion on dry/wet and synthetic/biological surfaces for a broad range of commercial applications. Shape complexity and performance of the existing structural adhesives are limited by the used specific fabrication technique, such as molding. To overcome these limitations by proposing complex 3D microstructured adhesive designs, a 3D elastomeric microstructure fabrication approach is implemented using two-photon-polymerization-based 3D printing. A custom aliphatic urethane-acrylate-based elastomer is used as the 3D printing material. Two designs are demonstrated with two combined biological inspirations to show the advanced capabilities enabled by the proposed fabrication approach and custom elastomer. The first design focuses on springtail- and gecko-inspired hybrid microfiber adhesive, which has the multifunctionalities of side-surface liquid super-repellency, top-surface liquid super-repellency, and strong reversible adhesion features in a single fiber array. The second design primarily centers on octopus- and gecko-inspired hybrid adhesive, which exhibits the benefits of both octopus- and gecko-inspired microstructured adhesives for strong reversible adhesion on both wet and dry surfaces, such as skin. This fabrication approach could be used to produce many other 3D complex elastomeric structural adhesives for future real-world applications.
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    [BMIM] [PF6] incorporation doubles CO2 selectivity of ZIF-8: elucidation of interactions and their consequences on performance
    (Amer Chemical Soc, 2016) N/A; N/A; N/A; N/A; N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Kınık, Fatma Pelin; Altıntaş, Çiğdem; Balcı, Volkan; Koyutürk, Burak; Uzun, Alper; Keskin, Seda; Master Student; Researcher; PhD Student; Master Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; N/A; N/A; N/A; 59917; 40548
    Experiments were combined with atomically detailed simulations and density functional theory (DFT) calculations to understand the effect of incorporation of an ionic liquid (IL), 1-n-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]), into a metal organic framework (MOF with a zeolitic imidazolate framework), ZIF-8, on the CO2 separation performance. The interactions between [BMIM] [PF6] and ZIF-8 were examined in deep detail, and their consequences on CO2/CH4, CO2/N-2, and CH4/N-2 separation have been elucidated by using experimental measurements complemented by DFT calculations and atomically detailed simulations. Results suggest that IL-MOF interactions strongly affect the gas affinity of materials at low pressure, whereas available pore volume plays a key role for gas adsorption at high pressures. Direct interactions between IL and MOF lead to at least a doubling of CO2/CH4 and CO2/N-2 selectivities of ZIF-8. These results provide opportunities for rational design and development of IL-incorporated MOFs with exceptional selectivity for target gas separation applications.
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    A communication theoretical modeling of single-layer graphene photodetectors and efficient multireceiver diversity combining
    (Ieee-Inst Electrical Electronics Engineers Inc, 2012) N/A; Department of Electrical and Electronics Engineering; Gülbahar, Burhan; Akan, Özgür Barış; PhD Student; Faculty Member; Department of Electrical and Electronics Engineering; Graduate School of Sciences and Engineering; College of Engineering; 234525; 6647
    Graphene with groundbreaking properties has tremendous impact on physical sciences as 2-D atomic layer carbon sheet. Its unique electronic and photonic properties lead to applications such as transistors, graphene photodetectors (GPDs), and electronic circuit components. Metal-graphene-metal (MGM) GPDs with single-or multilayer graphene sheets are promising for future nanoscale optical communication architectures because of wide range absorption from far infrared to visible spectrum, fast carrier velocity, and advanced production techniques due to planar geometry. In this paper, signal-to-noise ratio (SNR), bit-error rate (BER), and data rate performances of nanoscale single-layer symmetric MGM photodetectors are analyzed for intensity modulation and direct detection (IM/DD) modulation. Shot and thermal noise limited (NL) performances are analyzed emphasizing graphene layer width dependence and domination of thermal NL characteristics for practical power levels. Tens of Gbit/s data rates are shown to be achievable with very low BERs for single-receiver (SR) GPDs. Furthermore, multireceiver (MR) GPDs and parallel line-scan (PLS) network topology are defined improving the efficiency of symmetric GPDs. SNR performance of SR PLS channels are both improved and homogenized with MR devices having the same total graphene area by optimizing their positions with maxmin solutions and using maximal ratio and equal gain diversity combining techniques.