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Enhancing Nerve Regeneration in the Peripheral Nervous System Using Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2016 Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system Anup Dutt hS arma Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Biomedical Commons, Chemical Engineering Commons, and the Nanoscience and Nanotechnology Commons Recommended Citation Sharma, Anup Dutt, "Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system" (2016). Graduate Theses and Dissertations. 15082. https://lib.dr.iastate.edu/etd/15082 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system by Anup Dutt Sharma A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Chemical Engineering Program of Study Committee: Surya K. Mallapragada, Co-Major Professor Donald S. Sakaguchi, Co-Major Professor Balaji Narasimhan Kaitlin Bratlie Anumantha G. Kanthasamy Iowa State University Ames, Iowa 2016 Copyright © Anup Dutt Sharma, 2016. All rights reserved. ii TABLE OF CONTENTS ACKNOWLEDGEMENTS ................................................................................................. vii CHAPTER 1: RESEARCH OBJECTIVES ......................................................................... 1 1. Introduction ....................................................................................................................... 1 2. Summary ........................................................................................................................... 8 3. Organization of thesis ....................................................................................................... 8 4. References ......................................................................................................................... 9 CHAPTER 2: NEURAL TISSUE ENGINEERING: A REVIEW ................................... 12 1. Introduction ..................................................................................................................... 12 2. Surgical treatments.......................................................................................................... 15 3. Nerve regeneration conduits: Biomaterial approaches ................................................... 16 4. Cellular therapies ............................................................................................................ 21 5. Regenerative cues ........................................................................................................... 26 5.1. Topographical cues .................................................................................................. 26 5.2. Electrical cues .......................................................................................................... 27 5.3. Biomolecular cues .................................................................................................... 28 6. Nanomaterials ................................................................................................................. 31 6.1. Nano-scaffold design techniques ............................................................................. 33 6.2. Nano-structures ........................................................................................................ 38 7. Conclusions and future directions ................................................................................... 42 8. References ....................................................................................................................... 44 CHAPTER 3: ORIENTED GROWTH AND TRANSDIFFERENTIATION OF MESENCHYMAL STEM CELLS TOWARDS A SCHWANN CELL FATE ON MICROPATTERNED SUBSTRATES ............................................................................... 54 1. Abstract ........................................................................................................................... 54 2. Keywords ........................................................................................................................ 55 3. Introduction ..................................................................................................................... 55 4. Materials and methods .................................................................................................... 57 4.1. Fabrication of micropatterned polymeric films ....................................................... 57 4.2. Isolation of Brown Norway rat MSCs ..................................................................... 58 4.3. Culturing of Brown Norway rat MSCs .................................................................... 59 4.4. In vitro transdifferentiation of rat MSCs into SC-like phenotypes .......................... 60 4.5. Immunocytochemistry (ICC) ................................................................................... 61 4.6. Treatment with bromodeoxyuridine (BrdU) ............................................................ 63 iii 4.7. Data and statistical analysis ..................................................................................... 64 5. Results ............................................................................................................................. 65 5.1. Characterization of uMSCs ...................................................................................... 65 5.2. Fabrication of Polystyrene and Poly (lactic acid) films ........................................... 65 5.3. Effect of guidance cues on alignment and morphology of MSCs ........................... 67 5.4. Effect of guidance cues on proliferation of MSCs ................................................... 71 5.5. Effect of guidance cues on transdifferentiation of MSCs toward a SC-like phenotype. ....................................................................................................................... 72 6. Discussion ....................................................................................................................... 83 6.1. Transdifferentiation of MSCs .................................................................................. 84 6.2. Scaffolding and MSCs ............................................................................................. 86 7. Conclusions ..................................................................................................................... 88 8. Acknowledgements ......................................................................................................... 89 9. Supplemental material .................................................................................................... 90 10. References ..................................................................................................................... 95 CHAPTER 4: HIGH THROUGHPUT CHARACTERIZATION OF ADULT STEM CELLS ENGINEERED FOR DELIVERY OF THERAPEUTIC FACTORS FOR NEUROPROTECTIVE STRATEGIES ............................................................................. 98 1. Keywords ........................................................................................................................ 98 2. Short abstract .................................................................................................................. 98 3. Long abstract ................................................................................................................... 98 4. Introduction ................................................................................................................... 100 5. Protocol ......................................................................................................................... 101 5.1. Substrate Preparation for 96-well Plates ................................................................ 101 5.2. Cell Plating and Time-lapse Imaging .................................................................... 102 5.3. Ki67 Cell Proliferation and Propidium Iodide Live/Dead Assay .......................... 105 5.4. Automated Imaging and Multiwavelength Scoring Analysis ................................ 106 5.5. Cell Tracking ......................................................................................................... 107 6. Representative results ................................................................................................... 108 7. Discussion ..................................................................................................................... 117 8. Acknowledgements ....................................................................................................... 120 9. Disclosures .................................................................................................................... 120 10. References ..................................................................................................................
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