Browsing by Subject "Regenerative medicine"
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Item Open Access Bioactive supramolecular peptide nanofibers for regenerative medicine(Wiley, 2014) Arslan, Elif; Garip, I. Ceren; Gulseren, Gulcihan; Tekinay, Ayse B.; Güler, Mustafa O.Recent advances in understanding of cell-matrix interactions and the role of the extracellular matrix (ECM) in regulation of cellular behavior have created new perspectives for regenerative medicine. Supramolecular peptide nanofiber systems have been used as synthetic scaffolds in regenerative medicine applications due to their tailorable properties and ability to mimic ECM proteins. Through designed bioactive epitopes, peptide nanofiber systems provide biomolecular recognition sites that can trigger specific interactions with cell surface receptors. The present Review covers structural and biochemical properties of the self-assembled peptide nanofibers for tissue regeneration, and highlights studies that investigate the ability of ECM mimetic peptides to alter cellular behavior including cell adhesion, proliferation, and/or differentiation.Item Open Access Bioinspired materials for regenerative medicine and drug delivery applications(Bilkent University, 2016-10) Hamsici, SerenThe structural organization and functional capabilities of natural materials have inspired many technological and scientific developments. Biological systems are under constant pressure for innovation due to the constraints imposed by natural selection, which has allowed various organisms to surmount engineering challenges in ways that can scarcely be matched by modern science. Biomimetics or bioinspiration is a field that focuses on the adaptation of engineering principles observed in biological models to fabricate materials capable of circumventing longstanding problems in fields such as energy and medicine. This transition from biological systems has facilitated the design of effective materials, structures or processes within the range of nature’s adaptations and strategies. In the first study of this thesis, I describe the development of a bioactive scaffold composed of adamantyl-conjugated, laminin-derived bioactive IKVAV peptide molecules enmeshed in electrospun cyclodextrin nanofiber (CDNFs). Accordingly, host-guest interactions between adamantyl groups on peptide termini and cyclodextrin molecules on electrospun nanofiber surfaces were utilized to produce a composite material for the treatment of neurodegenerative disorders. Electrospun CDNFs provided a 3-dimensional environment conductive for the growth of PC12 cells and expressed functionalized bioactive epitopes on their surfaces to enhance the differentiation of neural progenitors. In addition, CDNFs further supported neural growth through their highly aligned mesh structure. Neural bIII tubulin and synaptophysin I gene expression levels significantly increased when PC12 cells were cultured on aligned and IKVAV-functionalized CDNFs. Neurite extension of PC12 cells also increased significantly when cultured on aligned and IKVAVfunctionalized CDNFs when compared to random and unfunctionalized electrospun CDNFs. As such, these nanofibers are able to effectively induce the neural differentiation of PC-12 cells through the physical and biochemical signals provided by their structure and bioactive sequence. The second part of the present thesis focuses on the local delivery of gemcitabine, a cytotoxic cancer drug that is rapidly degraded in plasma and cannot be encapsulated in conventional delivery vesicles due to its highly hydrophobic nature. In order to overcome these limitations, gemcitabine was coupled with Fmoc-Gly and integrated into a peptide-based nanocarier system in order to control drug concentration within the therapeutic range and minimize the adverse effects. Two oppositely-charged amyloid inspired peptides (Fmoc-AIPs) were chosen as drug carrier systems. These molecules self assemble into nanofiber structures at physiological conditions through non-covalent interactions. Overall, the present thesis demonstrates the significance of peptide-based materials for the purpose of designing functional bioinspired/biomimetic materials for various cellular applications such as tissue engineering and drug delivery. The complexity of nature necessitates the design of biomaterials that can mimic the cellular microenvironment for the treatment of diseases, and further insight into natural processes will no doubt enhance our ability to overcome the engineering challenges presented by modern medicine.Item Open Access Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine(American Chemical Society, 2016-03) Fais, S.; O'Driscoll, L.; Borras, F. E.; Buzas, E.; Camussi, G.; Cappello, F.; Carvalho, J.; Cordeiro Da Silva, A.; Del Portillo, H.; El Andaloussi, S.; Ficko Trček, T.; Furlan, R.; Hendrix, A.; Gursel, I.; Kralj-Iglic, V.; Kaeffer, B.; Kosanovic, M.; Lekka, M. E.; Lipps, G.; Logozzi, M.; Marcilla, A.; Sammar, M.; Llorente, A.; Nazarenko, I.; Oliveira, C.; Pocsfalvi, G.; Rajendran, L.; Raposo, G.; Rohde, E.; Siljander, P.; Van, N. G.; Vasconcelos, M. H.; Yáñez-Mó, M.; Yliperttula, M. L.; Zarovni, N.; Zavec, A. B.; Giebel, B.Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding of the plasma membrane. Nanosized EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions. Containing cell-type-specific signatures, EVs have been proposed as biomarkers in a variety of diseases. Furthermore, according to their physical functions, EVs of selected cell types have been used as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery. Undoubtedly, the rapidly emerging field of basic and applied EV research will significantly influence the biomedicinal landscape in the future. In this Perspective, we, a network of European scientists from clinical, academic, and industry settings collaborating through the H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD), demonstrate the high potential of nanosized EVs for both diagnostic and therapeutic (i.e., theranostic) areas of nanomedicine.Item Open Access A living material platform for the biomineralization of biosilica(Elsevier B.V., 2022-12-15) Kırpat Konak, Büşra Merve; Bakar, Mehmet Emin; Ahan, Recep Erdem; Özyürek, Emel Uzunoğlu; Dökmeci, Serap; Şafak Şeker, Urartu ÖzgürNature has a vast array of biomineralization mechanisms. The commonly shared mechanism by many living organisms to form hardened tissues is the nucleation of mineral structures via proteins. Living materials, thanks to synthetic biology, are providing many opportunities to program cells for many functionalities. Here we have demonstrated a living material system for biosilicification. Silaffins are utilized to synthesize silicified cell walls by one of the most abundant organism groups called diatoms. The R5 peptide motif of the silaffins is known for its ability to precipitate silica in ambient conditions. Therefore, various studies have been conducted to implement the silicification activity of R5 in different application areas, such as regenerative medicine and tissue engineering. However, laborious protein purification steps are required prior to silica nanoparticle production in recombinant approaches. In this study, we aimed to engineer an alternative bacterial platform to achieve silicification using released and bacteria-intact forms of R5-attached fluorescent proteins (FP). Hence, we displayed R5-FP hybrids on the cell surface of E. coli via antigen 43 (Ag43) autotransporter system and managed to demonstrate heat-controllable release from the surface. We also showed that the bacteria cells displaying R5-FP can be used in silicification reactions. Lastly, considering the stimulating effect of silica on osteogenic differentiation, we treated human dental pulp stem cells (hDPSCs) with the silica aggregates formed via R5-FP hybrids. Earlier calcium crystal deposition around the hDPSCs was observed. We envision that our platform can serve as a faster and more economical alternative for biosilicification applications, including endodontics. © 2022Item Open Access Materials for articular cartilage regeneration(Bentham Science Publishers B.V., 2012) Tombuloglu, Ayşegül; Tekinay, Ayşe B.; Güler, Mustafa O.Many health problems remaining to be untreatable throughout the human history can be overcome by utilizing new biomedical materials. Healing cartilage defects is one of the problems causing significant health issue due to low regeneration capacity of the cartilage tissue. Scaffolds as three-dimensional functional networks provide promising tools for complete regeneration of the cartilage tissue. Diversity of materials and fabrication methods give rise to many forms of scaffolds including injectable and mechanically stable ones. Various approaches can be considered depending on the condition of cartilage defect. A scaffold should maintain tissue function within a short time, and should be easily applied in order to minimally harm the body. This review will cover several patents and other publications on materials for cartilage regeneration with an outlook on essential characteristics of materials and scaffolds.Item Open Access Nanomaterials for medicine(John Wiley & Sons, 2016-03-11) Güler, Mustafa O.; Tekinay, Ayşe B.; Güler, Mustafa O.; Tekinay, Ayşe B.Nanomaterials with controlled physical, chemical, and biological characteristics can be used for the therapy of the specific causes of the diseases. There are several ways to develop new materials in nanometer scale. Mainly, top‐down and bottom‐up approaches are the two major techniques to produce nanomaterials. Depending on the application area, either one or both of these approaches can be used to develop materials that can be used in studying pathophysiology of diseases and their diagnosis and therapy. Especially, bioinspired and biomimetic strategies yield products that can replace or accommodate activities of the natural biomolecules. Nevertheless, for effective diagnosis and therapy of diseases, it is almost crucial to first understand the molecular reasons behind disease development. The nanomaterials can be also used in regenerative medicine applications. Although there have been extensive advances in developing nanomaterials for biomedical purposes, only few of them have been translated into clinics.Item Open Access Self-assembled one-dimensional soft nanostructures(Royal Society of Chemistry, 2010) Toksoz, S.; Acar, H.; Güler, Mustafa O.The self-assembly process is a bottom-up approach and is the spontaneous aggregation of many different subunits into well-defined functional structures with varying properties. Self-assembly is an attractive method to develop one-dimensional nanostructures and is controlled by many factors including temperature, pH and electrolyte addition. Novel self-assembled one-dimensional nanostructures are finding applications in regenerative medicine and electronics as well as in fabrication of nanoscale electronic, mechanic, magnetic, optical, and combinatorial devices. Their utility comes from their high ratio of surface area to volume, and their quantum-confinement effects. This paper reviews one-dimensional self-assembled organic nanostructures classified according to the noncovalent forces acting on their formation.