Browsing by Subject "Regeneration"
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Item 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.Item Open Access Development of bioactive peptide nanofibers for intervertebral disc regeneration(Bilkent University, 2017-08) Uysal, ÖzgeLower back pain (LBP) and neck problems are the most common orthopedic diseases worldwide, and the main reason behind LBP is intervertebral disc degeneration (IVDD). Therefore, specialized therapeutic applications to induce intervertebral disc (IVD) regeneration is a necessity. Here, we report the use of a collagen-mimetic bioactive peptide nanofiber scaffold (Col-PA/E-PA) for the improvement of disc regeneration by recapitulating the structure and function of the natural extracellular matrix (ECM) of intervertebral connective tissue. Following two weeks of degeneration, the bioactive nanofiber scaffold was topically applied and the IVD regeneration process was observed through histochemical analyses. The collagen-mimetic bioactive peptide nanofiber system was found to significantly promote glycosaminoglycan and collagen deposition at the site of injury compared to control nanofiber system and saline groups. In addition, the bioactive scaffold was consistently associated with lower values in degeneration scoring analyses, confirming the functional recovery of the tissue. Overall, the collagen-mimetic peptide nanofiber scaffold was able to prevent the progression of IVD degeneration and provide further functional recovery to the tissue.Item Open Access Laminin mimetic peptide nanofibers regenerate acute muscle defect(Acta Materialia Inc, 2017) Cimenci, C. E.; Uzunalli, G.; Uysal, O.; Yergoz, F.; Umay, E. K.; Güler, Mustafa O.; Tekinay, A. B.Skeletal muscle cells are terminally differentiated and require the activation of muscle progenitor (satellite) cells for their regeneration. There is a clinical need for faster and more efficient treatment methods for acute muscle injuries, and the stimulation of satellite cell proliferation is promising in this context. In this study, we designed and synthesized a laminin-mimetic bioactive peptide (LM/E-PA) system that is capable of accelerating satellite cell activation by emulating the structure and function of laminin, a major protein of the basal membrane of the skeletal muscle. The LM/E-PA nanofibers enhance myogenic differentiation in vitro and the clinical relevance of the laminin-mimetic bioactive scaffold system was demonstrated further by assessing its effect on the regeneration of acute muscle injury in a rat model. Laminin mimetic peptide nanofibers significantly promoted satellite cell activation in skeletal muscle and accelerated myofibrillar regeneration following acute muscle injury. In addition, the LM/E-PA scaffold treatment significantly reduced the time required for the structural and functional repair of skeletal muscle. This study represents one of the first examples of molecular- and tissue-level regeneration of skeletal muscle facilitated by bioactive peptide nanofibers following acute muscle injury. Significance Statement Sports, heavy lifting and other strength-intensive tasks are ubiquitous in modern life and likely to cause acute skeletal muscle injury. Speeding up regeneration of skeletal muscle injuries would not only shorten the duration of recovery for the patient, but also support the general health and functionality of the repaired muscle tissue. In this work, we designed and synthesized a laminin-mimetic nanosystem to enhance muscle regeneration. We tested its activity in a rat tibialis anterior muscle by injecting the bioactive nanosystem. The evaluation of the regeneration and differentiation capacity of skeletal muscle suggested that the laminin-mimetic nanosystem enhances skeletal muscle regeneration and provides a suitable platform that is highly promising for the regeneration of acute muscle injuries. This work demonstrates for the first time that laminin-mimetic self-assembled peptide nanosystems facilitate myogenic differentiation in vivo without the need for additional treatment.Item Open Access Role of FLT3 in the proliferation and aggressiveness of hepatocellular carcinoma(TÜBİTAK, 2016) Aydın, Muammer Merve; Bayın, Nermin Sumru; Acun, T.; Yakıcıer, M. C.; Akçalı, K. C.Background/aim: Previously we showed that Fms-like tyrosine kinase (FLT3) changes its cellular localization upon partial hepatectomy, suggesting a role in liver regeneration. FLT3 was also shown to play an important function in cellular proliferation and activation of PI3K and Ras. Thus, we aimed to investigate the role of FLT3 in hepatocellular tumorigenesis utilizing in vitro and in vivo models. Materials and methods: We used Snu398 cells that express FLT3. We investigated these cells in vitro proliferation and invasion abilities by treatment with the FLT3 inhibitor K-252a or by knocking-down with FLT3 shRNA,. Furthermore, the effect of blocking FLT3 activity and expression during in vivo tumorigenesis was assessed with xenograft models. Results: After K-252a treatment or stable knock-down, these cells proliferation and migration abilities were highly diminished in vitro. In addition, significant diminution in tumorigenicity of Snu398 cells was also obtained in vivo. When FLT3 knocked-down Snu398 cells were injected into nude mice, we did not detect αSMA expression in these tumors, suggesting a role for FLT3 in in vivo invasiveness. Conclusion: Our data provided evidence that FLT3 has a crucial role both in hepatocarcinogenesis and its invasiveness. Therefore, targeting FLT3 and/or its activity may be a promising tool for combating hepatocellular carcinomas.Item Open Access Supramolecular GAG-like self-assembled glycopeptide nanofibers Induce chondrogenesis and cartilage regeneration(American Chemical Society, 2016) Yaylaci, U. S.; Ekiz, M. S.; Arslan, E.; Can, N.; Kilic, E.; Ozkan, H.; Orujalipoor, I.; Ide, S.; Tekinay, A. B.; Güler, Mustafa O.Glycosaminoglycans (GAGs) and glycoproteins are vital components of the extracellular matrix, directing cell proliferation, differentiation, and migration and tissue homeostasis. Here, we demonstrate supramolecular GAG-like glycopeptide nanofibers mimicking bioactive functions of natural hyaluronic acid molecules. Self-assembly of the glycopeptide amphiphile molecules enable organization of glucose residues in close proximity on a nanoscale structure forming a supramolecular GAG-like system. Our in vitro culture results indicated that the glycopeptide nanofibers are recognized through CD44 receptors, and promote chondrogenic differentiation of mesenchymal stem cells. We analyzed the bioactivity of GAG-like glycopeptide nanofibers in chondrogenic differentiation and injury models because hyaluronic acid is a major component of articular cartilage. Capacity of glycopeptide nanofibers on in vivo cartilage regeneration was demonstrated in microfracture treated osteochondral defect healing. The glycopeptide nanofibers act as a cell-instructive synthetic counterpart of hyaluronic acid, and they can be used in stem cell-based cartilage regeneration therapies.Item Open Access Surface-modified bacterial nanofibrillar PHB scaffolds for bladder tissue repair(Taylor and Francis Ltd., 2016) Karahaliloǧlu, Z.; Demirbilek, M.; Şam, M.; Saǧlam, N.; Mizrak, A. K.; Denkbaş, E. B.The aim of the study is in vitro investigation of the feasibility of surface-modified bacterial nanofibrous poly [(R)-3-hydroxybutyrate] (PHB) graft for bladder reconstruction. In this study, the surface of electrospun bacterial PHB was modified with PEG- or EDA via radio frequency glow discharge method. After plasma modification, contact angle of EDA-modified PHB scaffolds decreased from 110 � 1.50 to 23 � 0.5 degree. Interestingly, less calcium oxalate stone deposition was observed on modified PHB scaffolds compared to that of non-modified group. Results of this study show that surface-modified scaffolds not only inhibited calcium oxalate growth but also enhanced the uroepithelial cell viability and proliferation.Item Restricted Yenikapı Mevlevihanesi üzerinden tekkeler ve tekke sanatı(Bilkent University, 2018) Özçelik, Elif; Aksu, Hazal; Uğuralp, Ahmet Kaan; Kahramanoğlu, Mustafa Furkan; Koca, OrkunOsmanlı’ da 14.yy. dan itibaren birçok tarikata ev sahipliği yapmış olan tekkelerden biri olan Yenikapı Mevlevihanesi, ibadet ve sanat gibi birçok amaç için kullanılmıştır. 1925 yılında Mustafa Kemal tarafından tekke ve zaviyelerin kapatılmasıyla birlikte diğer bütün tekkeler gibi Yenikapı da Osmanlı dönemindeki işlev ve özelliklerini yitirmiştir. Bununla beraber, ev sahipliği yaptığı sanatlar günümüzde ender de olsa varlığını sürdürmektedir.