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    A bi-layer electrospun polyurethane/silicone membrane scaffold: drug delivery and cytotoxicity studies
    (Indian Acad Sciences, 2023) Mohsenzadeh, Elham; Demir, Didem; Ceylan, Seda; Khenoussi, Nabyl; Schacher, Laurence; Adolphe, Dominique; Bolgen, Nimet
    In this study, a bi-layer scaffold combining polyurethane nanofibrous and silicone membrane layers was produced. Chemical, morphological and physical properties of the scaffolds were determined by Fourier-transform infrared spectroscopy, scanning electron microscope (SEM) and Brunauer-Emmett-Teller analyses, respectively. The surface properties were examined with the contact angle test. To evaluate the encapsulation and release behaviour of the scaffolds Rhodamine B and Nile red were used as model drugs. Further, the cytotoxicity and cell proliferation investigations were carried out using mouse embryonic fibroblasts cell lines. 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide assay and SEM were used to investigate the cell viability and cell-scaffold interactions, respectively. The results of the study were evaluated in order to develop a bimodal drug release system that has the potential to be used in tissue engineering applications.
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    Assessment of chitosan:gum tragacanth cryogels for tissue engineering applications
    (Wiley, 2022) Demir, Didem; Ugurlu, Muge Asik; Ceylan, Seda; Sakim, Burcu; Genc, Rukan; Bolgen, Nimet
    Gum tragacanth is one of the most widely used natural gums in food, medicine, cosmetics and personal care products, and its use as polysaccharide-based scaffolds in tissue engineering applications has attracted great attention in recent years. The fabrication of pure gum tragacanth as a scaffold poses many challenges because of the high viscosity, poor mechanical properties and repulsive interaction between the polyanions. To overcome these, facilitate the formation of scaffolds and improve their final properties, chitosan and gum tragacanth were used together as natural, biocompatible and biodegradable polysaccharides. The scaffolds based on chitosan and gum tragacanth were successfully fabricated through cryotropic gelation and were characterized using different chemical, morphological, mechanical and biocompatibility analyses. All cryogel scaffolds exhibited a porous structure with an average diameter of 96.56-30.21 mu m, exhibiting high liquid absorption capacity, appropriate mechanical stability and controlled degradation behavior. According to the biocompatibility results, mouse embryonic fibroblast cells adhered well to the scaffolds and achieved high viability. The results are also discussed in the light of their potential usefulness as a scaffold for tissue engineering applications. (c) 2022 Society of Industrial Chemistry.
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    Chitosan based injectable cryospheres as a potential biopolymeric carrier for drug delivery systems: Characterization, biocompatibility and drug release
    (Elsevier, 2024) Demir, Didem; Ceylan, Seda; Bolgen, Nimet
    Three-dimensional scaffolds with the right design to support cell metabolism and the right physico-chemical, mechanical, and biological qualities have become more interesting for tissue engineering because of the complexity and diversity of the tissues involved. Moreover, three-dimensional scaffolds with tuneable drug delivery capabilities have drawn more attention in the field of soft tissue engineering. In this research, chitosanbased microspheres (called cryospheres) were fabricated in spherical shapes micron-sized with highly interconnected porous structures as a result of combining emulsification and cryogelation methods. The characterization of cryospheres was evaluated using morphological, physicochemical, and biological analyses. According to the results of the in vitro and in vivo biocompatibility investigation, the microspheres had no toxic effects on cell survival, and they even enhanced cell viability at the implantation site when compared to the control group. After the cryospheres were characterized, research was done on drug loading, drug release, and release processes using two distinct dyes (Nile Red: NR and Rhodamine-B: RB) in simulated body fluids (simulated intestinal, stomach, and tear fluids). The results showed that the maximum drug loading capacities for RB and NR were 89.32 +/- 1.57 % and 61.51 +/- 0.70 %, respectively. This study contributed to the development of minimally invasive biomaterials that have the potential to provide both drug release and tissue formation/regeneration at damaged implantation sites by carrying not only drugs but also active substances such as hormones/growth factors that will trigger new tissue formation.
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    Composite Cryogels for Drug Delivery Applications: A Preliminary Study with Dye as a Model Drug
    (2023) Demir, Didem; Ceylan, Seda; Bolgen, Nimet
    Cryogels are suitable candidates to be used as drug release systems due to their interconnected pore structures, high surface areas, high liquid absorption capacities, and elasticity. With this purpose, we aimed to produce a cryogel structure to be used in drug release applications with the approach of tissue engineering. As biodegradable and biocompatible polymers chitosan and gelation were selected. The cryogels were fabricated using the combination of these polymers in the presence of glutaraldehyde under cryogenic conditions. The produced optimum gel scaffold was first characterized using FTIR, SEM, porosity, swelling ability, and degradation analyses. Successfully crosslinked gels exhibited an interconnected pore structure with an average pore diameter of 52.95 µm. As a result of the examination of the time-dependent weight change, it was also revealed that the cryogels have a liquid absorption capacity of about 500 times their dry weight and are biodegradable. The mainly characterized cryogel sample was evaluated for potential drug loading and release applications using methyl orange (MO) as a model drug. Gels, which swell in a short time, absorb the dye quickly and the cumulative release of the dye indicates that the gels are suitable for extended-release systems.
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    Design of gelatin cryogel scaffolds with the ability to release simvastatin for potential bone tissue engineering applications
    (Iop Publishing Ltd, 2024) Yaman, Suzan Melis; Demir, Didem; Bolgen, Nimet
    Tissue engineering aims to improve or restore damaged tissues by using scaffolds, cells and bioactive agents. In tissue engineering, one of the most important concepts is the scaffold because it has a key role in keeping up and promoting the growth of the cells. It is also desirable to be able to load these scaffolds with drugs that induce tissue regeneration/formation. Based on this, in our study, gelatin cryogel scaffolds were developed for potential bone tissue engineering applications and simvastatin loading and release studies were performed. Simvastatin is lipoliphic in nature and this form is called inactive simvastatin (SV). It is modified to be in hydrophilic form and converted to the active form (SVA). For our study's drug loading and release process, simvastatin was used in both inactive and active forms. The blank cryogels and drug-loaded cryogels were prepared at different glutaraldehyde concentrations (1, 2, and 3%). The effect of the crosslinking agent and the amount of drug loaded were discussed with morphological and physicochemical analysis. As the glutaraldehyde concentration increased gradually, the pores size of the cryogels decreased and the swelling ratio decreased. For the release profile of simvastatin in both forms, we can say that it depended on the form (lipophilic and hydrophilic) of the loaded simvastatin.
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    Electrospun Composite Nanofibers Based on Poly (epsilon-Caprolactone) and Styrax Liquidus (Liquidambar orientalis Miller) as a Wound Dressing: Preparation, Characterization, Biological and Cytocompatibility Results
    (Springer, 2022) Demir, Didem; Ozdemir, Sadin; Ceylan, Seda; Yalcin, M. Serkan; Sakim, Burcu; Bolgen, Nimet
    In this study, styrax liquidus (sweet gum balsam) extracted from Liquidambar orientalis Mill. incorporated PCL fibrous scaffolds were prepared using the electrospinning method. The effects of the styrax liquidus content on the prepared scaffolds were investigated using different physico-chemical and morphological analyses. Then, the styrax-loaded nanofibers were examined for their antioxidant activity, anti-biofilm, metal chelating, antimicrobial and DNA cleavage properties. The results obtained from these studies showed that the nanofibers exhibited effective biological activity depending on the weight ratio of the styrax liquidus. In light of the data obtained from the characterization and biological studies, a sample with high ratio of balsam was built for determining the cytocompatibility analysis in vitro. The cytotoxicity studies of the selected membrane were conducted using mouse embryonic fibroblast cells. The fibrous scaffolds lead to increase the cell number as a result of high viability. According to the results, we propose a novel biocompatible electrospun hybrid scaffold with antioxidant and antimicrobial properties that can be used as wound healing material for potential tissue engineering applications.
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    Electrospun Nanofibers for Biomedical, Sensing, and Energy Harvesting Functions
    (Mdpi, 2023) Demir, Didem; Bolgen, Nimet; Vaseashta, Ashok
    The process of electrospinning is over a century old, yet novel material and method achievements, and later the addition of nanomaterials in polymeric solutions, have spurred a significant increase in research innovations with several unique applications. Significant improvements have been achieved in the development of electrospun nanofibrous matrices, which include tailoring compositions of polymers with active agents, surface functionalization with nanoparticles, and encapsulation of functional materials within the nanofibers. Recently, sequentially combining fabrication of nanofibers with 3D printing was reported by our group and the synergistic process offers fiber membrane functionalities having the mechanical strength offered by 3D printed scaffolds. Recent developments in electrospun nanofibers are enumerated here with special emphasis on biomedical technologies, chemical and biological sensing, and energy harvesting aspects in the context of e-textile and tactile sensing. Energy harvesting offers significant advantages in many applications, such as biomedical technologies and critical infrastructure protection by using the concept of finite state machines and edge computing. Many other uses of devices using electrospun nanofibers, either as standalone or conjoined with 3D printed materials, are envisaged. The focus of this review is to highlight selected novel applications in biomedical technologies, chem.-bio sensing, and broadly in energy harvesting for use in internet of things (IoT) devices. The article concludes with a brief projection of the future direction of electrospun nanofibers, limitations, and how synergetic combination of the two processes will open pathways for future discoveries.
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    Optimization Studies of Cryogel Scaffolds Prepared Using Different Chitosan and Polyvinyl Alcohol Ratios
    (2023) Gül, Gülşah; Demir, Didem; Bolgen, Nimet
    Cryogels are scaffolds structured with interconnected porous matrices produced from frozen solutions of monomeric or polymeric initiators. These scaffolds are seen as unique candidates with desirable properties for the different biomedical fields including tissue engineering, wound dressing, and drug delivery systems. In this study, polyvinyl alcohol (PVA) and chitosan (CS) were used to fabricate PVA:CS composite cryogels. Cryogels prepared at different polymer ratios were evaluated in terms of chemical structure, morphology, porosity, and swelling ratio. The chemical structure of composite cryogels was determined using Fourier-transform infrared spectroscopy (FTIR). The interconnected pore morphology was observed using Scanning Electron Microscopy (SEM). Porosity and swelling ratio values were determined based on the weight change of the cryogels. In general, all samples exhibited a porous structure, and it was revealed that porosity and other properties differ according to the ratio of each polymer in the scaffolds.
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    Synergetic Integration of Electrospinning and Additive 3D/4D Printing Process for Biomedical Applications
    (Springer Science and Business Media Deutschland GmbH, 2023) Vaseashta, Ashok; Demir, Didem; Bolgen, Nimet
    Electrospinning is a versatile technique and has been used to produce porous fibers ranging from submicron to nanometer in diameter. Using a variety of high-performance polymers and blends, several new configurations are, now, possible for applications in tactile sensing, energy harvesting, filtration, and biomedical technologies. The structures, however, lack desired mechanical conformity, complexity, and single/multi-material three-dimensional rigid constructs essential to mimic specific functionalities. A simple, yet versatile, strategy is by employing a digitally controlled fabrication process of shape-morphing called 3D printing/additive manufacturing process and by conjoining the two promising technologies. Thus, using strategic and hierarchical integration of processes, elaborate shapes, and patterns can be fabricated on mesostructured stimuli-responsive electrospun membranes. The focus of this investigation is primarily on biomedical structures, as part of a large effort of precision and advanced manufacturing for rapid prototyping. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023.