Browsing by Author "Gülseren, Gülcihan"

Now showing 1 - 5 of 5

Open Access
Alkaline phosphatase-mimicking peptide nanofibers for osteogenic differentiation
(American Chemical Society, 2015) Gülseren, Gülcihan; Yasa, I. Ceren; Ustahuseyin, Oya; Tekin, E. Deniz; Tekinay, Ayse B.; Güler, Mustafa O.
Recognition of molecules and regulation of extracellular matrix synthesis are some of the functions of enzymes in addition to their catalytic activity. While a diverse array of enzyme-like materials have been developed, these efforts have largely been confined to the imitation of the chemical structure and catalytic activity of the enzymes, and it is unclear whether enzyme-mimetic molecules can also be used to replicate the matrix-regulatory roles ordinarily performed by natural enzymes. Self-assembled peptide nanofibers can provide multifunctional enzyme-mimetic properties, as the active sequences of the target enzymes can be directly incorporated into the peptides. Here, we report enhanced bone regeneration efficiency through peptide nanofibers carrying both catalytic and matrix-regulatory functions of alkaline phosphatase, a versatile enzyme that plays a critical role in bone formation by regulating phosphate homeostasis and calcifiable bone matrix formation. Histidine presenting peptide nanostructures were developed to function as phosphatases. These molecules are able to catalyze phosphate hydrolysis and serve as bone-like nodule inducing scaffolds. Alkaline phosphatase-like peptide nanofibers enabled osteogenesis for both osteoblast-like and mesenchymal cell lines.
Open Access
Catalytic and bioactive nanostructures for regenerative medicine applications
(2016-04) Gülseren, Gülcihan
Peptide nanostructures provide a remarkable toolbox for designing nature inspired smart materials. Synthetic peptide nanomaterials can be tailored with chemical, physical and biological signals to be utilized in a wide range of applications in biomedicine. With the increasing demand for complex nanostructures with facile preparation methods, bioinspired smart nanomaterials have gained more importance for achieving multifunctional hybrid materials. In particular, biological or chemical cues can be integrated into supramolecular designs to generate bioactive materials. This thesis describes nature inspired combinatorial methods for designing peptide nanostructures, which display catalytic and biologically functional moieties. These multifunctional peptide nanostructures were synthesized by using solid phase peptide synthesis. Designed peptide units were in accordance with the relevant biological function and they self-assemble to form nanofibrous networks mimicking the extracellular matrix. This combinatorial approach allows a wide range of applications including artificial catalysis, cell cultivation, biomineralization and live-cell labeling. In this thesis, the self-assembled catalytic and bioactive peptide nanostructures were utilized in artificial enzyme studies, biomineralization and tissue regeneration. The results show that these new artificial enzymes display both catalytic and biological functions of their natural counterparts such as proteins. In the first chapter, basic concepts of self-assembly, artificial catalysis approach, biomineralization and bioactive peptide nanostructures were explained. In the second chapter, multicomponent artificial catalyst model formed by self-assembly was investigated. Designed artificial peptide molecules were characterized structurally and catalytic capability of this de novo system was shown with both model and actual substrate. In the third chapter, ALP inspired catalytic, ion coordinating and biomineralizable peptide nanostructures were examined, bioactivity of this enzyme inspired materials was shown with multiple cell lines and using 2D and 3D cell culture methods. In the fourth chapter, enzyme responsive dentin sialophospho-protein like materials were exhibited instead artificial catalyst. Multi-responsive material induced biomineralization similar to dentin sialophospho-protein which controls mineralization during dentinogenesis. In the fifth part, peptide nanostructures were applied as bioorthogonal catalyst for live-cell tagging study, fluorophore tagged living cells by peptide catalyst was imaged by confocal microscopy. The last chapter covers novel materials inspired by unique nature of collagen and its bioregenerative capacity investigated with stem cells and preliminary cartilage induction was obtained.
Open Access
Collagen peptide presenting nanofibrous scaffold for intervertebral disc regeneration
(American Chemical Society, 2019) Uysal, Özge; Arslan, Elif; Gülseren, Gülcihan; Kılınç, M. C.; Doğan, İ.; Özalp, H.; Çağlar, Y. Ş.; Güler, M. O.; Tekinay, Ayşe B.
Lower back pain (LBP) is a prevalent spinal symptom at the lumbar region of the spine, which severely effects quality of life and constitutes the number one cause of occupational disability. Degeneration of the intervertebral disc (IVD) is one of the well-known causes contributing to the LBP. Therapeutic biomaterials inducing IVD regeneration are promising candidates for IVD degeneration treatments. Here, we demonstrate a collagen peptide presenting nanofiber scaffold to mimic the structure and function of the natural extracellular matrix of the tissue for IVD regeneration. The collagen peptide presenting nanofiber was designed by using a Pro-Hyp-Gly (POG) peptide sequence on a self-assembling peptide amphiphile molecule, which assembled into nanofibers forming scaffolds. Injection of collagen peptide presenting peptide nanofiber scaffold into the degenerated rabbit IVDs induced more glycosaminoglycan and collagen deposition compared to controls. Functional recovery of the tissue was evaluated by degeneration index score, where the bioactive scaffold was shown to provide functional recovery of the IVD degeneration. These results showed that the collagen peptide presenting nanofiber scaffold can prevent the progression of IVD degeneration and provide further functional recovery of the tissue.
Open Access
Dentin phosphoprotein mimetic peptide nanofibers promote biomineralization
(WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim, 2019) Gülseren, Gülcihan; Tansik, Gülistan; Garifullin, Ruslan; Tekinay, Ayse B.; Güler, Mustafa O.
Dentin phosphoprotein (DPP) is a major component of the dentin matrix playing crucial role in hydroxyapatite deposition during bone mineralization, making it a prime candidate for the design of novel materials for bone and tooth regeneration. The bioactivity of DPP‐derived proteins is controlled by the phosphorylation and dephosphorylation of the serine residues. Here an enzyme‐responsive peptide nanofiber system inducing biomineralization is demonstrated. It closely emulates the structural and functional properties of DPP and facilitates apatite‐like mineral deposition. The DPP‐mimetic peptide molecules self‐assemble through dephosphorylation by alkaline phosphatase (ALP), an enzyme participating in tooth and bone matrix mineralization. Nanofiber network formation is also induced through addition of calcium ions. The gelation process following nanofiber formation produces a mineralized extracellular matrix like material, where scaffold properties and phosphate groups promote mineralization. It is demonstrated that the DPP‐mimetic peptide nanofiber networks can be used for apatite‐like mineral deposition for bone regeneration.
Open Access
Nanomaterials for bone tissue regeneration and orthopedic implants
(John Wiley & Sons, 2016-03-11) Gülseren, Gülcihan; Ceylan, Hakan; Tekinay, Ayşe B.; Güler, Mustafa O.; Güler, Mustafa O.; Güler, Ayşe B.
Hierarchical organization and specialized composition of bone extracellular matrix (ECM) control the cellular processes including proliferation, migration, and differentiation for continuous modulation and maintenance of structure. For bone tissue regeneration, peptideor polymer‐based biomaterials have offered a framework to design interactive molecules displaying bone composite properties to mimic living bone tissue. This chapter reviews the structure and properties of peptide‐ and polymer‐based soft grafts for bone tissue regeneration, with a summary of upcoming goals and challenges in the future of these versatile materials. It basically covers types and applications of soft bone grafts, directed bone regeneration from biocompatible and bioactive biomaterials, and nanocomposite scaffolds for bone tissue regeneration. Bone regeneration studies have been primarily focused on polymers and synthetic proteins. The chapter describes some of the significant contribcutions to the field of bone regeneration with self‐assembled peptide structures.