Browsing by Author "Tekinay, Ayşe B."

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Open Access
Advances in nanoparticle‐based medical diagnostic and therapeutic techniques
(John Wiley & Sons, 2016-03-11) Sardan, Melis; Özkan, Alper Devrim; Zengin, Aygül; Tekinay, Ayşe B.; Güler, Mustafa O.; Güler, Mustafa O.; Tekinay, Ayşe B.
Advances in modern medicine have eliminated several major causes of human mortality and considerably extended life expectancies around the world; however, this increase in the global age average has also boosted the incidences of age‐associated disorders. These conditions, such as cancer, neurodegenerative disorders, and cardiovascular disease, severely decrease the quality of life for the affected but are highly polymorphic and often difficult to treat. This chapter describes the characteristics of nanoparticle (NP) contrast agents (CAs) proposed for use in medical imaging, and details the surface modification methods used to designate specific targets for their attachment. It then compares their effectiveness and toxicity compared to conventional methods of contrast enhancement, and discusses the contribution that nanoscience has had, and will have, on medical imaging and disease diagnosis at large.
Open Access
Bioactive peptide amphiphile nanofibers for cornea regeneration
(John Wiley & Sons, 2012) Uzunallı, Gözde; Soran, Zeliha; Dağtaş, Yavuz S.; Aydın, B.; Güler, Mustafa O.; Tekinay, Ayşe B.
Open Access
Bioactive self-assembled peptide nanofibers for corneal stroma regeneration
(Elsevier, 2014) Uzunallı, Gözde; Soran, Zeliha Soran; Erkal, Turan S.; Dagdas, Yavuz S; Dinc, E.; Hondur, A. M.; Bilgihan, K.; Aydin B.; Güler, Mustafa O.; Tekinay, Ayşe B.
Defects in the corneal stroma caused by trauma or diseases such as macular corneal dystrophy and keratoconus can be detrimental for vision. Development of therapeutic methods to enhance corneal regeneration is essential for treatment of these defects. This paper describes a bioactive peptide nanofiber scaffold system for corneal tissue regeneration. These nanofibers are formed by self-assembling peptide amphiphile molecules containing laminin and fibronectin inspired sequences. Human corneal keratocyte cells cultured on laminin-mimetic peptide nanofibers retained their characteristic morphology, and their proliferation was enhanced compared with cells cultured on fibronectin-mimetic nanofibers. When these nanofibers were used for damaged rabbit corneas, laminin-mimetic peptide nanofibers increased keratocyte migration and supported stroma regeneration. These results suggest that laminin-mimetic peptide nanofibers provide a promising injectable, synthetic scaffold system for cornea stroma regeneration.
Open Access
Biotin functionalized self‐assembled peptide nanofiber as an adjuvant for immunomodulatory response
(Wiley-VCH Verlag, 2020-12) Demircan, Muhammed Burak; Tohumeken, Sehmus; Gündüz, Nuray; Khalily, Mohammad Aref; Tekinay, T.; Güler, M. O.; Tekinay, Ayşe B.
Biotinylated peptide amphiphile (Biotin‐PA) nanofibers, are designed as a noncovalent binding location for antigens, which are adjuvants to enhance, accelerate, and prolong the immune response triggered by antigens. Presenting antigens on synthetic Biotin‐PA nanofibers generated a higher immune response than the free antigens delivered with a cytosine‐phosphate‐guanine oligodeoxynucleotides (CpG ODN) (TLR9 agonist) adjuvant. Antigen attached Biotin‐PA nanofibers trigger splenocytes to produce high levels of cytokines (IFN‐γ, IL‐12, TNF‐α, and IL‐6) and to exhibit a superior cross‐presentation of the antigen. Both Biotin‐PA nanofibers and CpG ODN induce a Th‐1‐biased IgG subclass response; however, delivering the antigen with Biotin‐PA nanofibers induce significantly greater production of total IgG and subclasses of IgG compared to delivering the antigen with CpG ODN. Contrary to CpG ODN, Biotin‐PA nanofibers also enhance antigen‐specific splenocyte proliferation and increase the proportion of the antigen‐specific CD8(+) T cells. Given their biodegradability and biocompatibility, Biotin‐PA nanofibers have a significant potential in immunoengineering applications as a biomaterial for the delivery of a diverse set of antigens derived from intracellular pathogens, emerging viral diseases such as COVID‐19, or cancer cells to induce humoral and cellular immune responses against the antigens.
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
Extracellular matrix mimetic peptide scaffolds for neural stem cell culture and differentiation
(Humana Press, 2014) Mammadov, Busra; Güler, Mustafa O.; Tekinay, Ayşe B.
Self-assembled peptide nanofibers form three-dimensional networks that are quite similar to fibrous extracellular matrix (ECM) in their physical structure. By incorporating short peptide sequences derived from ECM proteins, these nanofibers provide bioactive platforms for cell culture studies. This protocol provides information about preparation and characterization of self-assembled peptide nanofiber scaffolds, culturing of neural stem cells (NSCs) on these scaffolds, and analysis of cell behavior. As cell behavior analyses, viability and proliferation of NSCs as well as investigation of differentiation by immunocytochemistry, qRT-PCR, western blot, and morphological analysis on ECM mimetic peptide nanofiber scaffolds are described.
Open Access
Extracellular-matrix mimetic peptide nanofibers for neural regenerative medicine
(John Wiley & Sons, 2012) Tekinay, Ayşe B.; Mammadov, B.
Open Access
Generation of chimeric "aBS nanohemostat" complex and comparing its histomorphological in vivo effects to the traditional ankaferd hemostat in controlled experimental partial nephrectomy model
(Hindawi, 2013) Huri, Emre; Beyazit, Y.; Mammadov, Rashad; Toksoz, Sıla; Tekinay, Ayşe B.; Güler, Mustafa O.; Ustun H.; Kekilli, M.; Dadali, Mumtaz; Celik, T.; Astarci, M.; Haznedaroglu I.C.
Purpose. Using the classical Ankaferd Blood Stopper (ABS) solution to create active hemostasis during partial nephrectomy (PN) may not be so effective due to insufficient contact surface between the ABS hemostatic liquid agent and the bleeding area. In order to broaden the contact surface, we generated a chimeric hemostatic agent, ABS nanohemostat, via combining a self-assembling peptide amphiphile molecule with the traditional Ankaferd hemostat. Materials and Methods. In order to generate ABS nanohemostat, a positively charged Peptide Amphiphile (PA) molecule was synthesized by using solid phase peptide synthesis. For animal experiments, 24 Wistar rats were divided into the following 4 groups: Group 1: control; Group 2: conventional PN with only 0.5 ml Ankaferd hemostat; Group 3: conventional PN with ABS + peptide gel; Group 4: conventional PN with only 0.5 ml peptide solution. Results. Mean warm ischemia times (WITs) were 232.8 ± 56.3, 65.6 ± 11.4, 75.5 ± 17.2, and 58.1 ± 17.6 seconds in Group 1 to Group 4, respectively. Fibrosis was not different among the groups, while inflammation was detected to be significantly different in G3 and G4. Conclusions. ABS nanohemostat has comparable hemostatic efficacy to the traditional Ankaferd hemostat in the partial nephrectomy experimental model. Elucidation of the cellular and tissue effects of this chimeric compound may establish a catalytic spark and open new avenues for novel experimental and clinical studies in the battlefield of hemostasis. © 2013 Emre Huri et al.
Open Access
Growth and differentiation of pre-chondrogenic ATDC5 cells on bioactive self-assembled peptide nanofibers
(John Wiley & Sons, 2012) Üstün, Seher; Tombuloğlu, Ayşe; Uzunallı, Gözde; Güler, Mustafa O.; Tekinay, Ayşe B.
Open Access
Growth and differentiation of prechondrogenic cells on bioactive self-assembled peptide nanofibers
(American Chemical Society, 2013) Üstün, Seher; Tombuloğlu, Ayşegül; Kılınç, Murat; Güler, Mustafa O.; Tekinay, Ayşe B.
Restoration of cartilage defect remains a challenge, as the current treatments are ineffective to return tissue to its health. Thus, developing therapies for treatment of cartilage tissue damage caused by common joint diseases including osteoarthritis, rheumatoid arthritis, and accidents is crucial. Sulfated glycosaminoglycan molecules are vital constituents of both developing and mature cartilage extracellular matrix. The interplay between regulator proteins and glycosaminoglycan molecules has an essential role in coordinating differentiation, expansion, and patterning during cartilage development. In this study, we exploited the functional role of an extracellular matrix on chondrogenic differentiation by imitating extracellular matrix both chemically by imparting functional groups of native glycosaminoglycans and structurally through peptide nanofiber network. For this purpose, sulfonate, carboxylate, and hydroxyl groups were incorporated on self-assembled peptide nanofibers. We observed that when ATDC5 cells were cultured on functional peptide nanofibers, they rapidly aggregated in insulin-free medium and formed cartilage-like nodules and deposited sulfated glycosaminoglycans shown by Safranin-O staining. Moreover, collagen II and aggrecan gene expressions revealed by qRT-PCR were significantly enhanced, which indicated the remarkable bioactive role of this nanofiber system on chondrogenic differentiation. Overall, these results show that glycosaminoglycan mimetic peptide nanofiber system provides a promising platform for cartilage regeneration. © 2012 American Chemical Society.
Open Access
Growth factor binding on heparin mimetic peptide nanofibers
(American Chemical Society, 2012) Mammadov, Rashad; Mammadov, Busra; Güler, Mustafa O.; Tekinay, Ayşe B.
Immobilization of growth factors in scaffolds is important for controlling their dose and bioactivity for regenerative medicine applications. Although numerous covalent and noncovalent immobilization strategies have been proposed, better growth factor loading and dose control inside the scaffold is necessary. Nature of the binding site on the growth factor interacting with scaffold is critical for preserving and achieving maximal growth factor functionality, which has been a relatively less emphasized issue in previous studies. We recently reported heparin mimetic peptide nanofibers, which mimic chemistry of heparan sulfates. Heparin mimetic nanofibers were shown to bind to vascular endothelial growth factor (VEGF) and direct endothelial cells to angiogenesis. Here, we further investigated interactions between heparin mimetic peptide nanofibers and growth factors. We tested bioactivity of the nanofiber bound growth factors in order to understand the potential use of these peptide nanofiber scaffolds as analogues of heparan sulfates. We observed that heparin mimetic peptide nanofibers demonstrate better binding profiles to VEGF, hepatocyte growth factor (HGF), and fibroblast growth factor-2 (FGF-2) than control peptide nanofibers. We also identified that the heparin-binding domain of VEGF is critical for its interaction with these nanofibers. However, the heparin-binding site is not indispensable for binding of all growth factors to nanofibers. We also showed that binding of growth factors to nanofibers does not cause any loss in bioactivity through in vitro cell culture assays with PC-12 cells. These results reveal that heparin mimetic peptide nanofibers can effectively mimic heparan sulfates in extracellular matrix and provide an optimal milieu for spatial presentation of important growth factors. These properties make peptide nanofiber scaffolds promising materials for regenerative medicine applications through efficient and precisely controlled growth factor delivery. © 2012 American Chemical Society.
Open Access
Heparin mimetic peptide amphiphile nanofibers for angiogenesis
(John Wiley & Sons, 2012) Soran, Zeliha; Uzunallı, Gözde; Dağtaş, Yavuz S.; Tekinay, Ayşe B.; Güler, Mustafa O.
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.
Open Access
Mechanical properties of self-assembling peptide hydrogels and their effects on cell behaviors
(John Wiley & Sons, 2012) Çınar, Göksu; Ceylan, Hakan; Tekinay, Ayşe B.; Güler, Mustafa O.
Open Access
Mitochondrial serine protease HTRA2 p.G3999S in a kindred with essential tremor and Parkinson disease
(National Academy of Sciences, 2014) Gülümser, Hilal Ünal; Gulsuner, S.; Mercan, F. N.; Onat, Onur Emre; Walsh, T.; Shahin, H.; Lee, M. K.; Dogu, O.; Kansu, T.; Topaloglu, H.; Elibol, B.; Akbostanci, C.; King, M. C.; Özçelik, Tayfun; Tekinay, Ayşe B.
Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.
Open Access
Multifunctional peptide nanofiber scaffolds for neural differentiation
(John Wiley & Sons, 2012) Mammadov, B.; Erkal, Turhan Selman; Ürel, Mustafa; Güler, Mustafa O.; Tekinay, Ayşe B.
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
N-cadherin mimetic peptide nanofiber system induces chondrogenic differentiation of mesenchymal stem cells
(American Chemical Society, 2019) Çimenci, Çağla Eren; Uzunalli-Kurtuluş, G.; Çalışkan, Özüm S.; Güler, M. O.; Tekinay, Ayşe B.
Cadherins are vital for cell-to-cell interactions during tissue growth, migration, and differentiation processes. Both biophysical and biochemical inputs are generated upon cell-to-cell adhesions, which determine the fate of the mesenchymal stem cells (MSCs). The effect of cadherin interactions on the MSC differentiation still remains elusive. Here we combined the N-Cadherin mimetic peptide (HAV-PA) with the self-assembling E-PA and the resultant N-cadherin mimetic peptide nanofibers promoted chondrogenic differentiation of MSCs in conjunction with chondrogenic factors as a synthetic extracellular matrix system. Self-assembly of the precursor peptide amphiphile molecules HAV-PA and E-PA enable the organization of HAV peptide residues in close proximity to the cell interaction site, forming a supramolecular N-cadherin-like system. These bioactive peptide nanofibers not only promoted viability and enhanced adhesion of MSCs but also augmented the expression of cartilage specific matrix components compared to the nonbioactive control nanofibers. Overall, the N-cadherin mimetic peptide nanofiber system facilitated MSC commitment into the chondrogenic lineage presenting an alternative bioactive platform for stem-cell-based cartilage regeneration.
Open Access
Nanomaterials as tissue adhesives
(John Wiley & Sons, 2016-03-11) Yasa, İ. Ceren; Ceylan, Hakan; Tekinay, Ayşe B.; Güler, Mustafa O.; Güler, Mustafa O.; Tekinay, Ayşe B.
Tissue adhesives are used to create functional bonding interfaces between injured tissue parts and between tissues and implanted biomaterials. This chapter provides a critical review of the conventional tissue adhesive materials and their shortcomings. Then it concentrates on the design approaches of emerging tissue adhesive technologies, particularly those using nanotechnology, with a primary focus on their clinical applicability. Various classes of synthetic polymers have been developed and applied as tissue adhesivesTheir defined chemistry and tailorable material properties, such as adhesion strength, curing kinetics, and mechanical properties, drove the motivation in this approach. The two major classes of synthetic tissue adhesives discussed in the chapter are acrylate‐based adhesives and polyurethanes. Urethane‐based adhesives have also been considered for use as soft tissue adhesives or sealants, because of their thermal stability at physiological temperature and absence of hemolytic behavior.
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.