Title Page
Abstract
Contents
Chapter 1. Introduction (Theoretical review) 15
1.1. Study background 16
1.1.1. Study objective 16
1.1.2. Electroceuticals 18
1.1.3. Neural interfaces 20
1.2. Peripheral nerve injury 22
1.3. Spinal cord injury 28
Chapter 2. Peripheral nerve interface & electrical stimulation for regeneration of long nerve defect 31
2.1. Introduction 32
2.2. Experimental methods 39
2.3. Result and Discussion 49
2.3.1. Electroceutical platform composed of biodegradable conductive conduit and wireless electrical stimulator 49
2.3.2. Electrical and mechanical, and dissolution properties of Mo/PCL composites 55
2.3.3. Application examples of Mo/PCL composites 63
2.3.4. In-vitro test of Mo/PCL composites 66
2.3.5. In-vivo demonstration of electroceutical platform 68
2.4. Conclusion 81
Chapter 3. Spinal cord interface & electrical stimulation for rehabilitation of spinal cord contusion 83
3.1. Introduction 84
3.2. Experimental methods 87
3.3. Result and Discussion 95
3.3.1. Electroceutical consisted of neural interface electrode and wireless electrical stimulator 95
3.3.2. Electrical and mechanical properties of CB/Ecoflex composite electrode 100
3.3.3. In vitro test of CB/Ecoflex composites 109
3.3.4. In vivo demonstration of spinal cord treatment electroceutical 112
3.4. Conclusion 118
Chapter 4. Conclusion 120
4.1. Conclusion 121
References 123
Abstract (Korean) 133
Figure 1.1. Anatomy of peripheral nerve. 25
Figure 1.2. Intact axon image. 26
Figure 1.3. Seddon's classification of nerve injury a) Neuropraxia b) Axonotmesis c) Neurotmesis. 26
Figure 1.4. Wallerian degeneration process. 27
Figure 1.5. Nervous system of human. 30
Figure 2.1. Schematic image of electroceutical platform. 51
Figure 2.2. The rectifier circuit of the wireless electrical stimulator and external coil. 52
Figure 2.3. Schematic image of biodegradable conductive conduit. 53
Figure 2.4. a) Photograph of Mo/PCL conduit (tick mark: 1 mm) b) Cross-sectional SEM image of biodegradable and CNC (left), SEM... 53
Figure 2.5. Photograph of electroceutical platform. 54
Figure 2.6. Electrical properties of Mo/PCL composites. a) Electrical conductivity of Mo/PCL composites depending on the volume fraction... 58
Figure 2.7. Mechanical properties of Mo/PCL composites a) Uniaxial tensile stress-strain curves of Mo/PCL composites depending on the... 59
Figure 2.8. Dissolution properties of Mo/PCL composite a) Time-dependent electrical conductivity of Mo/PCL composites (20 vol.%... 62
Figure 2.9. a) Structure of a bone scaffold fabricated using the Mo/PCL composite. Inset shows an optical microscope image of the... 65
Figure 2.10. a) Conductive traces on a glass slide formed by direct printing of Mo/PCL dissolved in tetrahydrofuran (THF). b) Screen-... 65
Figure 2.11. Live/dead test on Mo/PCL. a) Fluorescence microscopy images of live/dead assay. Scale bar = 200 μm. b) Cell viability... 67
Figure 2.12. a) Surgical procedure for implanting integrated systems. From left to right: the skin is incised and nerve is transected with 10... 70
Figure 2.13. Verifying the signal transmitted through the implanted conductive nerve conduit. a) The experimental set up b) In vivo... 71
Figure 2.14. a) Sciatic functional index score for each week after transplantation for each group (n = 8). b) Sciatic static index score... 74
Figure 2.15. a) Wet weight measurement for each muscle type at injury site (n = 8). b) Wet weight for each muscle type at intact site.... 78
Figure 2.16. a) The transection points of sciatic nerve with conductive nerve conduit. b) Representative images of... 79
Figure 2.17. a) Luxol Fast Blue staining results for each area (-1mm, +5mm, +11mm) (n = 8). b) Measurements of the area of positively... 80
Figure 3.1. Schematic illustration of neural interface electrode. 97
Figure 3.2. Photograph of the electroceutical (left) and neural interface electrode (right). 98
Figure 3.3. Photograph of wireless power transmission for spinal cord stimulation. 99
Figure 3.4. Conductivity of CB/Ecoflex composites with various content of CB in Ecoflex 00-30. 102
Figure 3.5. Scanning electron microscope (SEM) images of CB/Ecoflex composites with 10, 12.5, 15 wt.% CB. 102
Figure 3.6. Viscosity of CB/Ecoflex composites at various content of CB at different shear rates. 103
Figure 3.7. a) Electrochemical impedance spectroscopy of CB/Ecoflex composites consisting of various volume fractions of CB.... 104
Figure 3.8. a) Tensile stress-strain curves of CB/Ecoflex composites depending on the contents of CB. (black, 0 wt.%; green, 10 wt.%;... 107
Figure 3.9. a) variation of electrical conductivity of CB/Ecoflex composite during uniaxial stretching with various content of CB. b)... 108
Figure 3.10. In-vitro cytotoxicity test. 110
Figure 3.11. Effectiveness of electrical stimulation at in-vitro. 111
Figure 3.12. a) Surgical procedure for implanting electroceutical. From left to right: the skin is incised and the laminectomy is... 113
Figure 3.13. The locomotor function of spinal cord injured rats after therapeutic-stimulated until 8 weeks. a) BBB score b) ladder score... 116
Figure 3.14. a) The histological images of H&E staining. b) The cavity size of injured spinal cord. c) Immunohistochemistry for ED-1... 117