Browsing by Subject "Sciatic nerve"

Now showing 1 - 2 of 2

Open Access
Development of peptide nanomaterials for neural regeneration
(2015-05) Mammadov, Büşra
Nervous 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.
Open Access
Peripheral nerve regeneration by synthetic peptide nanofibers
(2016-09) Geçer, Mevhibe
The peripheral nervous system (PNS) has a complex structure that consists of high numbers of nerve cells and communication networks between the central nervous system and the body parts. Unlike the central nervous system, the PNS exhibits a considerable capacity for regeneration; however, peripheral nerve injuries can nevertheless cause lifelong disability. Various methods are currently available for the treatment of nerve injuries, but autologous nerve grafting is considered as ‘the gold standard’. Donor site morbidity, neuroma formation and failure of functional recovery are some limitations of this technique, especially when used for the repair of long nerve gaps. Polymeric nerve conduits are clinically available alternatives to nerve grafting, and function by guiding the axonal growth and isolating the regenerating axon from the inhibitory environment present in the post-injury neuroma. In this thesis, we used peptide amphiphile molecules (PAs) that can self-assemble into the nanofibers and mimic both the structure and function of healthy ECM of nerve cells for sciatic nerve regeneration. Two bioactive PAs, LN-PA (derived from laminin) and GAG-PA (derived from glycosaminoglycan), were tested for their ability to induce neural regeneration in a rat sciatic nerve model. Hollow nerve conduits were filled with peptide nanofiber gels, and electrophysiology and histology results were compared with autologous graft treated groups. Our results show that bioactive peptide nanofibers are able to boost regeneration and functional motor and sensory recovery. Electromyography results demonstrated that better signal transmission was observed in peptide nanofiber treated groups compared with empty conduits and autograft treated groups. Histological assessments also confirmed that bioactive peptide nanofiber treated groups exhibited better axonal regeneration. These results suggest that these biologically active PA nanofiber gels may be used as a biomaterial for peripheral nerve regeneration in clinical practice.