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Development of an Implantable Electrical Stimulation Device for Bone Regeneration

DC Field Value Language
dc.contributor.advisor김성준-
dc.contributor.author김정훈-
dc.date.accessioned2017-07-13T07:05:14Z-
dc.date.available2017-07-13T07:05:14Z-
dc.date.issued2014-08-
dc.identifier.other000000021298-
dc.identifier.urihttps://hdl.handle.net/10371/119019-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 전기·컴퓨터공학부, 2014. 8. 김성준.-
dc.description.abstractElectrical stimulation modulates cellular process in a form of ionic current through regulating cell membrane potential. Electrical stimulation has effects of up-regulation of cell proliferation rate and cell viability. As a good osteoinductive tool, electrical stimulation has effects of differentiation to bone cell, acceleration of ossification and calcium induction that improve bone regeneration. Although implantable electrical stimulation devices for bone regeneration were commercialized, there was limitation for applying to bone graft transplantation due to the shape of the device and stimulation delivery.
In the present dissertation, implantable bone regeneration device using electrical stimulation is demonstrated. The device can deliver a concentrated electrical stimulation to three-dimensional bone graft. The evaluation of bone regeneration targeting animal bone defect model using the designed device is demonstrated.
As a preliminary step for developing bone regeneration device, a bioreactor device which allows intracorporeal cell culture using electrical stimulation was designed. Using this device, human mesenchymal stromal cell was cultured intracorporeally with electrical stimulation. The cell proliferation of the electrical stimulated stem cell was increased by 23% compared to the unstimulated stem cell. Also in the electrically stimulated group, stem cell had more stable adhesion to the collagen sponge and better extracellular matrix formation compare to the control group.
Through improvement of the bioreactor device, bone regeneration experiment targeting a rabbit mandible was executed by transplantation of stem cell graft and electrical stimulation device into the defect site. Polyimide electrode was designed to be suited the defect of animal and electrical current generator was packaged with silicone. The electrical stimulated group showed a higher bone volume by 260% compared with unstimulated group. Also electrical stimulated group showed better new bone formation results in various bone parameters.
Then LCP-based bone regeneration device was designed with a built-in electrical current generator and wireless power receiver device. LCP has good hermeticity and good osseo-integration property. This device performs a graft containment system and electrical stimulation device simultaneously.
From these results, bone regeneration treatment using implantable bone regeneration device which can apply electrical stimulation to defect site directly can be an effective and new methods for bone defect recovery. Furthermore, it can be expected that development of implantable bone regeneration device using LCP and development of combined treatment of intracorporeal stem cell culture and electrical stimulation.		-
dc.description.tableofcontentsAbstract i

Contents iii

List of Figures v

List of Tables vii

Chapter 1 Introduction 1
1.1 Regulation of cellular process through electrical stimulation 1
1.1.1 Charge transfer at interface of electrode/electrolyte 3
1.1.2 Electrical equivalent circuit modeling of cellular membrane 7
1.1.3 Gating mechanisms of ion channels 19
1.1.3.1 Voltage-gated ion channel 21
1.1.3.2 Ligand-gated ion channel 21
1.1.3.3 Second messenger gated ion channel 23
1.1.3.4 Mechanosensitive ion channel 24
1.1.3.5 Light sensitive ion channel 27
1.1.3.6 Temperature sensitive ion channel 29
1.1.4 Cellular processes generated by change of transmembrane potential 32
1.1.4.1 Generation of action potential 32
1.1.4.2 Intracellular second messenger signaling pathway 36
1.2 Bone regeneration using electrical stimulation 38
1.2.1 Bone regeneration process by electrical stimulation 38
1.2.2 Clinical studies of bone regeneration using direct current stimulation 40
1.2.3 Development progress of direct current stimulator for bone regeneration 42
1.3 Bone regeneration therapy 47
1.3.1 Existing bone regeneration therapies 47
1.3.2 Bone regeneration therapy using stem cell graft 49
1.4 LCP as bone substitute 50
1.5 Objectives of the dissertation 52


Chapter 2 Materials and Methods 54
2.1 Implantable bioreactor device 54
2.1.1 Device configuration 54
2.1.2 Bioreactor using titanium electrode 60
2.1.3 Bioreactor using polyimide electrode 62
2.1.4 In vivo cell proliferation experiment 65
2.1.4.1 Preparation of collagen sponge 65
2.1.4.2 Preparation of hMSCs 66
2.1.4.3 Process of animal experiment 67
2.1.5 Assessment of cell proliferation 69
2.1.5.1 MTT assay 69
2.1.5.2 Scanning electron microscopy (SEM) 69
2.1.5.3 Reverse transcription=polymerase chain reaction (RT-PCR) 70
2.2 Implantable electrical stimulation device for bone regeneration 71
2.2.1 Configuration of bone regeneration device 71
2.2.2 Electrode for bone regeneration of rabbit mandible 72
2.2.3 Preperation of collagen sponge 73
2.2.4 hBMSCs culture 73
2.2.5 Preperation of hydrogel 74
2.2.6 Preperation of PCL containment system 75
2.2.7 Animal experiment 76
2.2.7.1 Animal experiment configuration 76
2.2.7.2 Animal experiment process 77
2.2.8 Assessment of bone regeneration 79
2.2.8.1 Soft x-ray 79
2.2.8.2 micro CT 80
2.2.8.3 Histochemical staining 81
2.3 LCP based implantable bone regeneration device 82
2.3.1 Device configuration 82
2.3.2 LCP layers for bone regeneration device 85
2.3.2.1 Electrode layer 85
2.3.2.2 Inductive coil layer 87
2.3.2.3 PCB layer 88
2.3.2.4 Other layers 89
2.3.3 Heat press process and heat formation process 90

Chapter 3 Results 93
3.1 Cell proliferation using implantable bioreactor 93
3.2 Bone regeneration results using bone regeneration device 97
3.2.1 Radiological and histological examinations 97
3.2.2. Micro CT analysis 99

Chapter 4 Discussion 101
4.1 Implantable bone regeneration device for bone graft transplantation therapy 101
4.2 Selection of the electrical stimulation parameters 102
4.3 An alternative tissue engineering method of in situ stem cell therapy using intracorporeal cell culture 104
4.4 Transfer of electrical stimulation according to electrode design of bioreactor 106
4.5 Bone regeneration effect on combined treatment of electrical stimulation and 108
4.6 Potential for chronic bone substitute of LCP-based bone regeneration device LCP 110
Chapter 5 Conclusion 113

References 114

Abstract in Korean 121		-
dc.formatapplication/pdf-
dc.format.extent6035464 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectElectrical stimulation-
dc.subjectimplantable device-
dc.subjectbone regeneration-
dc.subjectstem cell-
dc.subjectLCP-
dc.subject.ddc621-
dc.titleDevelopment of an Implantable Electrical Stimulation Device for Bone Regeneration-
dc.typeThesis-
dc.description.degreeDoctor-
dc.citation.pagesviii, 122-
dc.contributor.affiliation공과대학 전기·컴퓨터공학부-
dc.date.awarded2014-08-
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