Browsing by Subject "Neural regeneration"
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Item Open Access Bioactive nanomaterials for neural engineering(Springer, Cham, 2016) Sever, Melike; Uyan, İdil; Tekinay, Ayse B.; Güler, Mustafa O.; Zhang, L. G.; Kaplan, D. L.Nervous system is a highly complex interconnected network and higher organisms including humans have limited neural regeneration capacity. Neurodegenerative diseases result in significant cognitive, sensory, or motor impairments. Following an injury in the neural network, there is a balance between promotion and inhibition of regeneration and this balance is shifted to different directions in central nervous system (CNS) and peripheral nervous system (PNS). More regeneration capacity is observed in the PNS compared to the CNS. Although, several mechanisms play roles in the inhibitory and growth-promoting natures of the CNS and PNS, extracellular matrix (ECM) elements are key players in this process. ECM is a three-dimensional environment where the cells migrate, proliferate, and differentiate (Rutka et al. 1988; Pan et al. 1997). After a comprehensive investigation of the interactions between the ECM proteins and cell receptors, the ECM environment was found to regulate significant cellular processes such as survival, proliferation, differentiation, and migration (Yurchenco and Cheng 1994; Aszodi et al. 2006). Its components have major roles not only in neurogenesis during development of the nervous system but also in normal neural functioning during adulthood (Hubert et al. 2009).Item Open Access Biocompatible electroactive tetra (aniline)-conjugated peptide nanofibers for neural differentiation(American Chemical Society, 2018) Arioz, Idil; Erol, Ozlem; Bakan, Gokhan; Dikecoglu, F. Begum; Topal, Ahmet E.; Urel, Mustafa; Dana, Aykutlu; Tekinay, Ayse B.; Güler, Mustafa O.Peripheral nerve injuries cause devastating problems for the quality of patients' lives, and regeneration following damage to the peripheral nervous system is limited depending on the degree of the damage. Use of nanobiomaterials can provide therapeutic approaches for the treatment of peripheral nerve injuries. Electroactive biomaterials, in particular, can provide a promising cure for the regeneration of nerve defects. Here, a supramolecular electroactive nanosystem with tetra(aniline) (TA)-containing peptide nanofibers was developed and utilized for nerve regeneration. Self-assembled TA-conjugated peptide nanofibers demonstrated electroactive behavior. The electroactive self-assembled peptide nanofibers formed a well-defined three-dimensional nanofiber network mimicking the extracellular matrix of the neuronal cells. Neurite outgrowth was improved on the electroactive TA nanofiber gels. The neural differentiation of PC-12 cells was more advanced on electroactive peptide nanofiber gels, and these biomaterials are promising for further use in therapeutic neural regeneration applications.Item Open Access Development of peptide nanomaterials for neural regeneration(Bilkent University, 2015-05) Mammadov, BüşraNervous system consists of a dense network of cells and their connections and exhibits a high level of complexity. This complexity arises from the high variety of cell types with very specific functions, the high number of cells along with the abundance of connections between these cells. When combined with the nonproliferative nature of neural cells and inhibitory nature of the pathological extracellular matrix (ECM), this complexity leads to a very limited regenerative potential. Thus neurodegenerative disorders and traumatic injuries of neural tissues lead to lifelong disabilities due to the poor success of current therapies. Novel therapeutic approaches which can overcome barriers that impede neural regeneration are therefore required to be developed. Smartly designed nanomaterials that can direct cells towards desired functions can improve the regeneration of neural tissues. Herein, I have described my work on development of peptide nanofibers for neuroregeneration and biological applications of these nanomaterials. To achieve the regeneration of the nervous system, the composition of the neural ECM under healthy conditions and during early development was mimicked through structural resemblance and bioactive epitope presentation using nanofibers. Laminin derived IKVAV peptide sequence and glycosaminoglycan mimicking, growth factor-binding sulfonated peptide sequence were presented on peptide nanofiber scaffolds. Differentiation of PC-12 cells, a model cell system for neuroregenerative studies, was found to be improved on these nanofiber scaffolds when compared to the cells on epitope free control scaffolds. Cells could even extend neurites on these scaffolds in the presence of inhibitory chondroitin sulfate proteoglycans. These nanofibers also proved to be efficient in sciatic nerve regeneration after injury. When injected into the lumen of polymeric nerve guidance channels, this bioactive nanofiber system provided guidance to the elongating axons and resulted in better axonal regeneration that was evident both from histological analysis and electromyography results. Results of in vitro and in vivo experiments were correlated and indicated the neuroregenerative potential of these peptide nanofibers. In addition, semiconductive oligothiophene was encapsulated in peptide nanofibers without compromising the biocompatibility. These hybrid nanofiber scaffolds can potentially be used for electrical stimulation of neurons that can further boost regeneration.Item Open Access Investigation of spontaneous differentiation of neural stem cells on synthetic scaffolds(Bilkent University, 2017-08) Uyan, İdilDespite the increasing incidents of brain injuries and neurodegenerative diseases, a definitive clinical therapy for these conditions has not been found yet. Nervous system injuries result in loss of neural cells, causing loss of function in the neural circuitry. As mature neurons do not divide, it is not possible to tolerate the loss of neurons by the production of new ones. In the central nervous system, even though neural stem cells are present, their number and regenerative capacity are very low. In addition, inhibitory molecules are released at the degeneration site which hinders reconnection of the remaining cells. As the damage is due to the loss of neurons, cell therapy is considered as a promising option. Neural stem cells are capable of differentiating into the three major cell types in the central nervous system: neurons, astrocytes, and oligodendrocytes. However, due to low rate of survival of the transplanted cells, there is still a need for a cell vehicle system to promote their survival, adhesion, migration, and differentiation. On the other hand, use of biological molecules such as growth factors or extracellular matrix proteins as vehicle systems should be minimized due to the immunological risks. Nanotechnological approaches serve as a great opportunity to mimic the native environment of the cells. Peptide amphiphiles (PAs) are self-assembling molecules that provide precise control over their secondary structure and the amino acid sequence, which can mimic proteins and show hydrogel properties. In this thesis, self-assembling PA scaffolds that mimic laminin, heparan sulfate and cadherin, which are key players in nervous system regeneration, have been investigated as cell delivery vehicles. Neurospheres are great models for studying the behavior of neural stem cells within a heterogeneous 3-dimensional cell population. Migration and differentiation behavior of neurospheres were investigated on laminin (LN), heparan sulfate (GAG), and cadherin-mimetic (HAV) PA nanofiber scaffolds. The results indicated that LN and GAG mimicking PA scaffolds cooperatively enhanced the migration of neurospheres, whereas cadherin mimetic PA scaffolds were individually sufficient to promote their migration. Also, a fine neural network was observed to be established on HAV-PA. These scaffolds hold high potential to be used as cell delivery vehicles.Item Open Access Nanomaterials for neural regeneration(John Wiley & Sons, 2016-03-11) Sever, Melike; Mammadov, Büşra; Geçer, Mevhibe; Güler, Mustafa O.; Tekinay, Ayşe B.; Güler, Mustafa O.; Tekinay, Ayşe B.The central nervous system (CNS) consists of a dense network of cells leaving a smaller volume for the extracellular matrix (ECM) components (10‐20% for the brain unlike most other tissues (Cragg, 1979)). The reaction of the nervous tissue to any injury leading to scar tissue formation acts as a barrier for regeneration in the CNS, while it supports regeneration in the peripheral nervous system (PNS). By mimicking several unique characteristics of the natural environment of cells, synthetic materials for neural regeneration can be improved chemically and biologically. Especially bioactivation of materials can be achieved by addition of small chemical moieties to the scaffold particularly found in specific tissues or addition of biologically active molecules derived from natural ECM. The ECM‐derived short peptides are promising candidates to be presented as functional domains on the scaffold surface for use in neural regeneration.