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Stroke is a medical condition in which poor blood flow to the brain results in cell death. The current treatment options are limited and only very few patients can benefit from these treatments. Stroke causes brain swelling and often a decompressive craniectomy is performed for some of the patients to release intracranial pressure to prevent further damage. As a result, a duraplasty is implanted to replace the surgically-damaged dura mater to protect the brain. In view of that, the purpose of this project was to develop double-walled microspheres (DWMS) which can be used as a drug delivery system when incorporated into duraplasty to promote endogenous stem cell therapy to treat stroke. The DWMS were composed of poly (l-lactic acid) (PLLA) and poly (lactic-co-glycolic acid) (PLGA) using a solvent evaporation method. Bovine serum albumin (BSA), as a model protein, was entrapped within these DWMS with different core-shell thicknesses and compositions to investigate the distribution of protein, encapsulation efficiency, and in vitro release. The fabrication process parameters of DWMS were also optimized to attain higher yields, and the phase separation and surface morphology were examined by differential scanning calorimetry and scanning electron microscopy.

Endogenous neural stem/progenitor cells therapy is one of the most advanced clinical trial worldwide. Generally, drug is given to the targeted area through the traditional strategies such as intraventricular or intravenous delivery method. However, those methods always come with undesired side-effects such as over-dose of drug and offensive injection are not applicable to the large-scale clinical application. In this study, the clinical feasibility of blended biosynthesized cellulose duraplasty was studied. Our results showed that physical properties of BBC can be controlled through the optimized fabrication process. In addition, the time length of Middle cerebral artery occlusion rat model was tested through the 60 vs 90 mins occlusion time behavioral assessments of rat and the data indicated that 60 mins length can induce significant motor functional impairment. Finally, the EGF & EPO-loaded BBC duraplasty was implanted over the removed area and the ELISA test revealed that BBC duraplasty can release and delivery the growth factors to the targeted area (subvertical zone) at least 3 days after implantation. In summary, our BBC duraplasty is showing the potential prospection to be a clinical-applicable duraplasty to replace the traditional commercial duraplasty in the future stroke recovery therapy.

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.