Browsing by Author "Tansik, G."

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Open Access
A glycosaminoglycan mimetic peptide nanofiber gel as an osteoinductive scaffold
(Royal Society of Chemistry, 2016) Tansik, G.; Kilic, E.; Beter, M.; Demiralp, B.; K.Sendur, G.; Can, N.; Ozkan, H.; Ergul, E.; Güler, Mustafa O.; Tekinay, A. B.
Biomineralization of the extracellular matrix (ECM) plays a crucial role in bone formation. Functional and structural biomimetic native bone ECM components can therefore be used to change the fate of stem cells and induce bone regeneration and mineralization. Glycosaminoglycan (GAG) mimetic peptide nanofibers can interact with several growth factors. These nanostructures are capable of enhancing the osteogenic activity and mineral deposition of osteoblastic cells, which is indicative of their potential application in bone tissue regeneration. In this study, we investigated the potential of GAG-mimetic peptide nanofibers to promote the osteogenic differentiation of rat mesenchymal stem cells (rMSCs) in vitro and enhance the bone regeneration and biomineralization process in vivo in a rabbit tibial bone defect model. Alkaline phosphatase (ALP) activity and Alizarin red staining results suggested that osteogenic differentiation is enhanced when rMSCs are cultured on GAG-mimetic peptide nanofibers. Moreover, osteogenic marker genes were shown to be upregulated in the presence of the peptide nanofiber system. Histological and micro-computed tomography (Micro-CT) observations of regenerated bone defects in rabbit tibia bone also suggested that the injection of a GAG-mimetic nanofiber gel supports cortical bone deposition by enhancing the secretion of an inorganic mineral matrix. The volume of the repaired cortical bone was higher in GAG-PA gel injected animals. The overall results indicate that GAG-mimetic peptide nanofibers can be utilized effectively as a new bioactive platform for bone regeneration. © 2016 The Royal Society of Chemistry.
Open Access
Mineralized peptide nanofiber gels for enhanced osteogenic differentiation
(Wiley, 2018) Eren, E. D.; Tansik, G.; Tekinay, A. B.; Güler, Mustafa O.
Mineral deposition is observed in both bacterial and eukaryotic organisms through a broad range of mechanisms. Both organic and inorganic components play crucial roles in the formation of mineralized tissues, and acidic proteins are particularly important in this context owing to their ability to stimulate nucleation of minerals. Here, we present negatively-charged self-assembling peptide amphiphile molecules as a template to nucleate calcium phosphate mineralization in a bioactive scaffold environment. Acidic peptide molecules were shown to induce formation of hydroxyapatite like calcium phosphate mineralization, which was characterized by scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, X-ray diffractometry, oscillatory rheology and atomic force microscopy. The osteoblast-like cells were found to reveal enhanced osteogenic differentiation on pre-mineralized peptide nanofiber networks, suggesting that mineral deposition can be used as a means of enhancing the bioactivity of peptide-based scaffold systems.
Open Access
Nanomechanical characterization of osteogenic differentiation of mesenchymal stem cells on bioactive peptide nanofiber hydrogels
(Wiley-VCH Verlag, 2017-08) Topal, A. E.; Tansik, G.; Ozkan A.D.; Güler, Mustafa O.; Dana, A.; Tekinay, A. B.
Stem cell differentiation is known to be influenced by the mechanical properties of the surrounding extracellular matrix (ECM); however, little is known about the mechanical phenotypes of differentiating stem cells within the ECM. Here, this study uses osteoinductive, ECM-mimetic peptide nanofibers to investigate the changes in the mechanical properties of rat mesenchymal stem cells (rMSCs) during osteogenic differentiation. In addition, octafluorocyclobutane (C4F8)-coated atomic force microscopy (AFM) cantilevers are developed to minimize tip–sample adhesion during the nanomechanical characterization of rMSCs, and osteogenic differentiation is monitored through molecular analysis in conjunction with AFM measurements. rMSCs cultured on osteoinductive peptide nanofibers differentiate at substantially higher rates, form osteogenic cell clusters, deposit calcium to the surrounding matrix, and strikingly increase their Young's moduli throughout the osteogenic differentiation process compared to controls. These results show that the elasticity profiles of differentiating rMSCs may change significantly depending on environmental factors and especially the degree of biomineralization, and that the natural elasticity responses of cells cultured on scaffolds may be considerably different from those observed on non-bioactive surfaces. This is important for the identification of cell elasticity as a biophysical marker of osteogenic differentiation of MSCs, and indicates that biomineralization might have a predominant role on cell mechanics.