Browsing by Subject "Nerve growth factor"

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    Design and application of nerve growth factor-β binding peptide nanofibers for neural regeneration
    (2016-11) Orhan, Zeynep
    Promotion of neurite outgrowth is an important limiting step for the regeneration of nerve injury and depends strongly on the local expression of nerve growth factor (NGF). Rational design of bioactive materials is a promising approach for the development of novel therapeutic methods for nerve regeneration, and biomaterials capable of presenting NGF to nerve cells are especially suitable for this purpose. This thesis describes development of nanofibrous peptide amphiphile (PA) nanofibers capable of promoting neurite outgrowth by displaying high density binding epitopes for NGF. The high-affinity NGF-binding sequence was identified by phage display and combined with a beta-sheet forming motif to produce a self-assembling PA molecule. Our results revealed that the bioactive nanofiber had higher affinity for NGF compared to control nanofiber and in vitro studies showed that the NGF binding peptide amphiphile nanofibers (NGFB-PA nanofiber) significantly promote the neurite outgrowth of PC-12 cells. In addition, the nanofibers induced differentiation of PC-12 cells into neuron-like cells by enhancing NGF/high-activity NGF receptor (TrkA) interactions and activating MAPK pathway elements. The first time with this study a seven amino acid phage display peptide library was utilized for high affinity epitope screening for NGF, the NGF binding sequence was incorporated into peptide amphiphile structure, and the effect of NGF binding material on differentiation pathway of NGF was analyzed. This material will pave the way for development of new therapeutic agents for nervous system injuries.
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    Protein-releasing conductive anodized alumina membranes for nerve-interface materials
    (Elsevier Ltd, 2016) Altuntas, S.; Buyukserin, F.; Haider, A.; Altinok, B.; Bıyıklı, Necmi; Aslim, B.
    Nanoporous anodized alumina membranes (AAMs) have numerous biomedical applications spanning from biosensors to controlled drug delivery and implant coatings. Although the use of AAM as an alternative bone implant surface has been successful, its potential as a neural implant coating remains unclear. Here, we introduce conductive and nerve growth factor-releasing AAM substrates that not only provide the native nanoporous morphology for cell adhesion, but also induce neural differentiation. We recently reported the fabrication of such conductive membranes by coating AAMs with a thin C layer. In this study, we investigated the influence of electrical stimulus, surface topography, and chemistry on cell adhesion, neurite extension, and density by using PC 12 pheochromocytoma cells in a custom-made glass microwell setup. The conductive AAMs showed enhanced neurite extension and generation with the electrical stimulus, but cell adhesion on these substrates was poorer compared to the naked AAMs. The latter nanoporous material presents chemical and topographical features for superior neuronal cell adhesion, but, more importantly, when loaded with nerve growth factor, it can provide neurite extension similar to an electrically stimulated CAAM counterpart.
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    Sciatic nerve regeneration induced by glycosaminoglycan and laminin mimetic peptide nanofiber gels
    (Royal Society of Chemistry, 2016) Mammadov, B.; Sever, M.; Gecer, M.; Zor, F.; Ozturk, S.; Akgun, H.; Ulas, U. H.; Orhan, Z.; Güler, Mustafa O.; Tekinay, A. B.
    In the USA, 20 million patients suffer from neuropathy caused by peripheral nerve injuries, which costs approximately 150 billion annually. For longer nerve gaps and multiple injury sites, it is essential to use nerve guidance conduits for healthy pathfinding of regenerating axons. Here, extracellular matrix mimetic peptide nanofiber hydrogels were used for functionalizing guidance conduits to enhance neuronal regeneration in the distal stump of full transaction sciatic nerve injury in rats with functional repair. Conduits filled with heparan sulfate and laminin mimetic peptide nanofibers significantly improved electromyography response and promoted neuronal regeneration in a rat model of sciatic nerve defect. In addition, Schwann cells cultured on these nanofibers showed increased viability and significantly enhanced nerve growth factor (NGF) release. Overall, these results suggest that extracellular matrix mimetic peptide nanofibers present a promising treatment option for peripheral nerve injuries.
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    Three-Dimensional Laminin Mimetic Peptide Nanofiber Gels for In Vitro Neural Differentiation
    (Wiley-VCH Verlag, 2017) Gunay, Gokhan; Sever, Melike; Tekinay, Ayse B.; Güler, Mustafa O.
    The extracellular matrix (ECM) provides biochemical signals and structural support for cells, and its functional imitation is a fundamental aspect of biomaterial design for regenerative medicine applications. The stimulation of neural differentiation by a laminin protein-derived epitope in two-dimensional (2D) and three-dimensional (3D) environments is investigated. The 3D gel system is found to be superior to its 2D counterpart for the induction of neural differentiation, even in the absence of a crucial biological inducer in nerve growth factor (NGF). In addition, cells cultured in 3D gels exhibits a spherical morphology that is consistent with their form under in vivo conditions. Overall, the present study underlines the impact of bioactivity, dimension, and NGF addition, as well as the cooperative effects thereof, on the neural differentiation of PC-12 cells. These results underline the significance of 3D culture systems in the development of scaffolds that closely replicate in vivo environments for the formation of cellular organoid models in vitro. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim