Browsing by Author "Kocabey, Samet"

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Open Access
Biomimetic self-assembled peptide nanofibers for bone regeneration
(2012) Kocabey, Samet
Self-assembled peptide nanofibers are exploited in regenerative medicine applications due to their versatile, biofunctional and extracellular-matrixresembling structures. These properties provide peptide nanofibers with osteoinductive and osteoconductive behaviors for bone regeneration applications through several approaches. In this thesis, two different approaches were discussed, which were developed to induce bone regeneration and mineralization including extracellular matrix mimicking peptide nanofibers based 2-D gel formation and surface functionalization of titanium implants. For this purpose, we designed glycosaminoglycan-mimetic peptide nanofibers inspired by chemical structure of glycosaminoglycans present in the bone extracellular matrix. We demonstrated that glycosaminoglycan-mimetic peptide nanofibers interact with BMP-2, a critical growth factor for osteogenic activity. Glycosaminoglycan-mimicking ability of the peptide nanofibers and their interaction with BMP-2 promoted osteogenic activity of and mineralization by osteoblastic cells. ALP activity, Alizarin Red Staining and EDAX spectroscopy indicated efficacy of the peptide nanofibers for inducing mineralization. We also developed a hybrid osteoconductive system for titanium biomedical implants inspired by mussel adhesion mechanism in order to overcome bone tissue integration problems. For this purpose, Dopa conjugated peptide nanofiber coating was used along with bioactive peptide sequences for osteogenic activity to enhance osseointegration of titanium surface. Dopamediated immobilization of osteogenic peptide nanofibers on titanium surfaces created an osteoconductive interface between osteoblast-like cells and inhibited adhesion and viability of soft tissue forming fibroblasts compared to the uncoated titanium substrate. In summary, osteoinductive and osteoconductive self-assembled peptide nanofibers were developed to promote osteogenic activity and mineralization of osteogenic cells. These bioactive nanofibers provide a potent platform in clinical applications of bone tissue engineering.
Open Access
Bone-like mineral nucleating peptide nanofibers induce differentiation of human mesenchymal stem cells into mature osteoblasts
(American Chemical Society, 2014) Ceylan, Hakan; Kocabey, Samet; Gulsuner, Hilal Unal; Balcik, O. S.; Güler, Mustafa O.; Tekinay, Ayse B.
A bone implant should integrate to the tissue through a bone-like mineralized interface, which requires increased osteoblast activity at the implant-tissue boundary. Modification of the implant surface with synthetic bioinstructive cues facilitates on-site differentiation of progenitor stem cells to functional mature osteoblasts and results in subsequent mineralization. Inspired by the bioactive domains of the bone extracellular matrix proteins and the mussel adhesive proteins, we synthesized peptide nanofibers to promote bone-like mineralization on the implant surface. Nanofibers functionalized with osteoinductive collagen I derived Asp-Gly-Glu-Ala (DGEA) peptide sequence provide an advantage in initial adhesion, spreading, and early commitment to osteogenic differentiation for mesenchymal stem cells (hMSCs). In this study, we demonstrated that this early osteogenic commitment, however, does not necessarily guarantee a priority for maturation into functional osteoblasts. Similar to natural biological cascades, early commitment should be further supported with additional signals to provide a long-term effect on differentiation. Here, we showed that peptide nanofibers functionalized with Glu-Glu-Glu (EEE) sequence enhanced mineralization abilities due to osteoinductive properties for late-stage differentiation of hMSCs. Mussel-inspired functionalization not only enables robust immobilization on metal surfaces, but also improves bone-like mineralization under physiologically simulated conditions. The multifunctional osteoinductive peptide nanofiber biointerfaces presented here facilitate osseointegration for long-term clinical stability. © 2014 American Chemical Society.
Open Access
Glycosaminoglycan mimetric peptide nanofibers promote mineralization by osteogenic cells
(Elsevier, 2013) Kocabey, Samet; Ceylan, Hakan; Tekinay, Ayse B.; Güler, Mustafa O.
Bone tissue regeneration is accomplished by concerted regulation of protein-based extracellular matrix components, glycosaminoglycans (GAGs) and inductive growth factors. GAGs constitute a significant portion of the extracellular matrix and have a significant impact on regulating cellular behavior, either directly or through encapsulation and presentation of growth factors to the cells. In this study we utilized a supramolecular peptide nanofiber system that can emulate both the nanofibrous architecture of collagenous extracellular matrix and the major chemical composition found on GAGs. GAGs and collagen mimetic peptide nanofibers were designed and synthesized with sulfonate and carboxylate groups on the peptide scaffold. The GAG mimetic peptide nanofibers interact with bone morphogenetic protein-2 (BMP-2), which is a critical growth factor for osteogenic activity. The GAG mimicking ability of the peptide nanofibers and their interaction with BMP-2 promoted osteogenic activity and mineralization by osteoblastic cells. Alkaline phosphatase activity, Alizarin red staining and energy dispersive X-ray analysis spectroscopy indicated the efficacy of the peptide nanofibers in inducing mineralization. The multifunctional and bioactive microenvironment presented here provides osteoblastic cells with osteogenic stimuli similar to those observed in native bone tissue.
Open Access
Hierarchical design of bone extracellular matrix mimetic nanofibers promote osteogenic differentiation of mesenchymal stem cells
(John Wiley & Sons, 2012) Ceylan, Hakan; Kocabey, Samet; Ünal, H.; Üstün, S.
Open Access
Mussel-inspired functionalization of metal surfaces with bioactive self-assembled peptide nanofibers
(John Wiley & Sons, 2012) Ceylan, Hakan; Kocabey, Samet; Güler, Mustafa O.; Tekinay, Ayşe B.
Open Access
Peptide nanofiber scaffolds for multipotent stromal cell culturing
(Humana Press Inc., 2013) Üstün, Seher; Kocabey, Samet; Güler, Mustafa O.; Tekinay, Ayse B.
Self-assembled peptide nanofibers are versatile materials providing suitable platforms for regenerative medicine applications. This chapter describes the use of peptide nanofibers as extracellular matrix mimetic scaffolds for two-dimensional (2D) and three-dimensional (3D) multipotent stromal cell culture systems and procedures for in vitro experiments using these scaffolds. Preparation of 2D and 3D peptide nanofiber scaffolds and cell culturing procedures are presented as part of in vitro experiments including cell adhesion, viability, and spreading analysis. Analysis of cellular differentiation on peptide nanofiber scaffolds is described through immunocytochemistry, qRT-PCR, and other biochemical experiments towards osteogenic and chondrogenic lineage. © Springer Science+Business Media New York 2013.