Delivery Systems to Enhance Neural Regeneration in the Central Nervous System

• Main Author: Stumpf da Silva, Taisa Regina
• Other Authors: Cao, Xudong
• Format: Others
• Language: en
• Published: Université d'Ottawa / University of Ottawa 2019
• Subjects: biosynthesized cellulose; stroke; duraplasty; spinal cord injury; nerve guidance tube; PC12; NSPC; branched peptides; RGDS
• Online Access: http://hdl.handle.net/10393/39391; http://dx.doi.org/10.20381/ruor-23635

The central nervous system (CNS) is susceptible to several disorders that can affect the structure or function of the brain or spinal cord, such as stroke and spinal cord injury (SCI). CNS disorders are complex, frequently causing failure of cognitive, motor and sensory functions. Unfortunately, there are only a few care alternatives for patients with CNS disorders, due to the limited capacity of the CNS to spontaneously regenerate; what expresses the need to develop innovative solutions, such as scaffolds that also could act as drug delivery systems to promote tissue and functional repairs in the CNS. To achieve this goal, three main projects were developed in this thesis. In the first project, a novel drug releasing duraplasty that can be applied as part of decompressive craniectomy (DC) was designed and tested. While DC can significantly reduce the risk of death, this procedure does not reverse the stroke damage. Thus, biosynthesized cellulose (BC) was used to produce a new duraplasty loaded with growth factors. The in vivo animal studies revealed that our duraplasty had excellent biocompatibility when implanted onto rodents’ brains. In the second project, BC tubes were prepared and nerve growth factor was incorporated into the tubes to be used as potential nerve guides to assist with the reconstitution of nerve tissues across SCI lesion. Physical and mechanical properties of the drug delivery systems produced were evaluated and compared to the neural native tissue. In addition, cell cultures demonstrated that growth factors released from both drug delivery systems were bioactive for over 7 days. In the third project, linear and 2-branched peptides were synthesized as potential bioactive molecules to improve tissue regeneration. These peptides, containing the RGDS sequence, were synthesized through Solid Phase Peptide Synthesis and characterized by mass spectrometry, high-performance liquid chromatography, and their conformational structures were analyzed by an energy minimized 3D model. In summary, this thesis explores the use of BC as drug releasing systems, which are promising and clinically relevant strategies to enhance nerve regeneration for many patients facing physical, mental and financial strains due to stroke, SCI or other difficult-to-cure injuries to the CNS.