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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/89793完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張博鈞 | zh_TW |
| dc.contributor.advisor | Po-Chun Chang | en |
| dc.contributor.author | 杜哲彰 | zh_TW |
| dc.contributor.author | Che-Chang Tu | en |
| dc.date.accessioned | 2023-09-22T16:08:19Z | - |
| dc.date.available | 2023-11-09 | - |
| dc.date.copyright | 2023-09-22 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-07-19 | - |
| dc.identifier.citation | Aemaimanan, P., Amimanan, P., & Taweechaisupapong, S. (2013). Quantification of key periodontal pathogens in insulin-dependent type 2 diabetic and non-diabetic patients with generalized chronic periodontitis. Anaerobe, 22, 64-68.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/89793 | - |
| dc.description.abstract | 研究目的：
牙周再生就理論來說是可行的，但是臨床變因如系統性疾病和咬合不正等會影響療效，因此跨專科協同治療或組織工程輔助療法常是必須的。而跨科治療，如矯正治療的介入，讓牙周再生的結果增添許多變數，組織工程輔助療法對於復原能力受損病患額外助益也尚不明瞭。因此，本研究瞭解矯正治療對牙周再生效果的影響，並探討脂肪幹細胞植入的組織工程輔助治療是否具促進嚴重糖尿病患牙周再生之效果。 研究材料與方法： 矯正治療對牙周再生效果的影響 搜集近十年（2008年至2019年）在台大醫院接受矯正治療並具骨下缺損病患，並依牙周再生手術後矯正治療開始的時間、移動方向、與牙周再生術式進行分組，分析治療前後缺損處平均牙周囊袋探測深度（Probing depth, PD）及臨床附連高度（Clinical Attachment Level, CAL）之變化。 脂肪幹細胞促進糖尿病患牙周再生之效果 經由抽脂法取得脂肪組織並分離出人類脂肪幹細胞 (Adipose-derived Stem Cells, ADSC)，檢查其多能性基因的表現及三系（骨系、軟骨系、脂系）分化的能力後，製作ADSC細胞球（ADSC spheres, ADsp）、包覆於微生物轉谷氨酰胺酶交聯之明膠水凝膠（microbial Transglutaminase-Crosslinked Gelatin Hydrogel, mTG）後，驗證其幹性的維持性。 我們以糖尿病大鼠大型口腔粘膜傷口和顱蓋骨缺損模擬牙周軟硬組織缺損，分別植入有無預先骨分化處理的ADsp、ADsp-mTG後，4-28天內對粘膜傷口進行臨床觀察、組織學評估和免疫組織化學染色分析細胞增生和角質化能力，並於第7天和第28天對骨缺損進行顯微斷層掃描影像分析、組織學評估和免疫組織化學染色分析細胞增生和成骨分化的能力。 研究結果： 矯正治療對牙周再生效果的影響 共計21位患者41處缺損區納入分析。牙周再生手術後早期（小於8週）和晚期（大於24週）進行矯正治療在PD減少和CAL增加均有顯著改善，但兩者間無統計學上顯著的意義。相較於移出骨缺損與單純牙齒排列組，牙齒移入骨缺損組有顯著較多的PD減少和CAL增加。不同牙周再生術式間療效無顯著差異。 脂肪幹細胞促進糖尿病患牙周再生之效果 ADSC表現多能性基因並能夠進行三系分化。ADSC在mTG 中可以維持其形態與幹性。在糖尿病粘膜傷口中，無預先骨分化處理的ADsp和ADsp-mTG 在傷口癒合、上皮化及角質化速度上都有較佳的表現。在糖尿病鼠骨缺損中，在預先骨分化處理的ADsp-mTG治療，成骨分化標的有明顯表現，細胞增殖能力在第7天即有增強，在第28天的時候有顯著較佳的骨生成。 結論： 本研究證實在牙周再生手術後進行矯正有助改善牙周狀況，特別是將牙齒移入缺損方向時，且無論早晚期進行牙齒移動均不會對於再生有不良影響。ADSC對於糖尿病的黏膜缺損與骨缺損均可顯著促進再生，亟具發展為臨床牙周再生輔助療程之潛力。 | zh_TW |
| dc.description.abstract | Periodontal regeneration is theoretically feasible but may be affected by clinical variables such as systemic diseases and malocclusion. Interdisciplinary collaborative treatment or tissue engineering adjunctive therapies are often necessary. However, the benefit of interdisciplinary treatment, such as orthodontic intervention or tissue engineering adjunctive therapies for patients with compromised regenerative capacity are still unclear. This study aims to understand the impact of orthodontic treatment on the effectiveness of periodontal regeneration and investigate whether adjunctive therapy with adipose-derived stem cell implantation promotes periodontal regeneration in diabetes.
Materials and Methods Impact of Orthodontic Therapy on Periodontal Regeneration Collecting data from patients who underwent orthodontic treatment and had bone defects at National Taiwan University Hospital between 2008 and 2019, we categorized them into groups based on the timing of orthodontic treatment initiation after periodontal regeneration surgery, the direction of tooth movement, and the periodontal regeneration technique. The changes in the average pocket probing depth (PD) and clinical attachment level (CAL) at the defect sites before and after treatment were analyzed. Adipose-Derived Stem Cells Application for Diabetic Periodontal Regeneration Human adipose-derived stem cells (ADSCs) were isolated. The expression of pluripotency genes and the differentiation capacity into three lineages (osteogenic, chondrogenic, and adipogenic) were examined. ADSC spheres (ADsp) were developed by self-aggregation and encapsulated with microbial transglutaminase-crosslinked gelatin hydrogel (mTG). The stemness of ADSCs in mTG was verified. The components of soft and hard tissue defects of periodontal defects were simulated by using creating oral mucosal wounds and calvarial bone defects in diabetic rats. ADsp with or without osteogenic pretreatment, or ADsp-mTG were delivered to the wounds/defects. Clinical observations, histological evaluations, and immunohistochemical staining for cell proliferation and keratinization were performed within 4-28 days on the mucosal wounds. Micro-computed tomography imaging analysis, histological evaluations, and immunohistochemical staining for cell proliferation and osteogenic differentiation were performed on the bone defects at day 7 and day 28. Results Promotion of Periodontal Regeneration by Orthodontic Therapy A total of 21 patients with 41 defect sites were included. Both Early (< 8 weeks) and late (> 24 weeks) orthodontic treatment following periodontal regeneration showed significant improvement in PD reduction and CAL gain, and there was no statistically significant difference between these time points. Compared to the group of move-out-defect and group of simple alignment, the group with tooth movement into the bone defects exhibited significantly greater PD and CAL gain. There was no significant difference in treatment effectiveness among different periodontal regeneration techniques. Adipose-Derived Stem Cells Application for Diabetic Periodontal Regeneration ADSCs expressed pluripotency genes and were capable of trilineage differentiation. ADSCs maintained their morphology and stemness in the mTG. In diabetic mucosal wounds, ADsp and ADsp-mTG without osteogenic pretreatment accelerated wound healing, epithelialization, and keratinization. In diabetic rat bone defects, treatment with pre-osteogenic ADsp-mTG demonstrated significant expression of osteogenic differentiation markers and cell proliferation capacity was enhanced as early as day 7, and by day 28, there was a significant improvement in bone formation. Conclusion This study indicated that orthodontic treatment was beneficial for periodontal regeneration, especially when teeth are moved into the defect. The timing of tooth movement seemed not have any adverse effects on regeneration. ADSCs significantly promoted mucosal and bone regeneration in diabetic animals, revealing the potential for developing as a novel adjunctive modality for periodontal regeneration. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-09-22T16:08:19Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-09-22T16:08:19Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | Content
口試委員會審定書 I 誌謝 II 中文摘要 III 英文摘要 V INTRODUCTION 1 CHAPTER 1 : THE NEEDS FOR PERIODONTAL REGENERATION 1 1.1 FUNDAMENTALS OF PERIODONTAL REGENERATION 1 1.2 PERIODONTAL REGENERATION IN SUPPORT OF ORTHODONTIC THERAPY 4 1.2.1 Timing of orthodontic tooth movement 6 1.2.2 Direction of Orthodontic Tooth Movement 9 1.3 PERIODONTAL REGENERATION IN THE MEDICALLY COMPROMISED CONDITION 10 1.3.1 Diabetes and Wound Healing 12 1.3.2 Diabetes and Periodontal Wound Healing 15 1.3.3 Stem Cell Therapy in Diabetic Wound Healing 19 CHAPTER 2 : TREATMENT STRATEGIES FOR PERIODONTAL REGENERATION 24 2.1 CURRENT STRATEGIES OF PERIODONTAL REGENERATION 24 2.1.1 Nonresorbable Membranes for GTR 24 2.1.2 Bioresorbable Membranes for GTR 26 2.1.3 Bone Replacement Grafts (BRGs) 28 2.1.4 Bioactive Molecules 33 2.2 PROSPECTIVE STRATEGIES OF PERIODONTAL AND BONE REGENERATION 35 2.2.1 Biomimetic Scaffolds 36 2.2.2 Stem Cells 43 2.2.2.1 Embryonic Stem Cells (ESCs) 45 2.2.2.2 Mesenchymal Stem Cells (MSCs) 46 2.2.2.3 Stem Cells of Dental Origin 49 2.2.2.4 Adipose-Derived Stem Cells (ADSCs) 55 2.2.2.5 Induced Pluripotent Stem Cells (iPSCs) 60 2.2.2.6 Matrix for Stem Cell Delivery 62 2.2.2.7 Stem cell Application in Periodontal Regeneration 65 CHAPTER 3 : RESEARCH GOALS 70 3.1 HYPOTHESES 72 3.2 SPECIFIC AIMS 73 3.3 SCIENTIFIC RATIONALE FOR OUR STUDIES 74 CHAPTER 4 : MATERIALS AND METHODS 76 4.1 PROMOTION OF PERIODONTAL REGENERATION BY ORTHODONTIC THERAPY 76 4.1.1 Ethical approval and the design of the study 76 4.1.2 Clinical Procedures and Measurements 78 4.1.3 Grouping Criteria and Statistical Analysis 80 4.2 ADIPOSE-DERIVED STEM CELLS APPLICATION FOR DIABETIC PERIODONTAL REGENERATION 82 4.2.1 Ethical Statements 83 4.2.2 ADSC isolation 84 4.2.3 Characterization of ADSCs 85 4.2.3.1 Expression of pluripotent markers 85 4.2.3.2 Trilineage differentiation 87 4.2.4 Preparation and characterization of ADsp-mTG 89 4.2.4.1 Preparation of ADsp-mTG 89 4.2.4.2 Behaviors of ADsp in mTG 90 4.2.4.3 Osteogenic induction of ADSCs 91 4.2.5 Preclinical validation 92 4.2.5.1 The induction of diabetes and randomization 92 4.2.5.2 The mucosal wound model 94 4.2.5.2.1 Gross observation of mucosal wounds 96 4.2.5.2.2 Histologic and immunohistochemical assessments of mucosal wounds 98 4.2.5.3 The osseous defect model 102 4.2.5.3.1 Micro-CT Assessments of the Osseous Defects 104 4.2.5.3.2 Histologic and immunohistochemical Assessments of the Osseous Defects 105 4.2.6 Statistical analysis 107 CHAPTER 5: RESULTS 109 5.1 PROMOTION OF PERIODONTAL REGENERATION BY ORTHODONTIC THERAPY 109 5.1.1 Patients and defects characteristics 109 5.1.2 Timing of orthodontic tooth movement 111 5.1.3 Directions of orthodontic tooth movement 113 5.1.4 Regeneration Protocols 114 5.1.5 The Preferable Protocol for Better Clinical Outcomes 115 5.2 ADIPOSE-DERIVED STEM CELLS APPLICATION FOR DIABETIC PERIODONTAL REGENERATION 117 5.2.1 Characterization of ADSCs 117 5.2.2 Characterization of ADsp-mTG 118 5.2.3 The Induction of Diabetes in Rats 119 5.2.4 The effect of ADsp-mTG on diabetic oral mucosal wounds 120 5.2.4.1 Gross Observation 120 5.2.4.2 Histologic and immunohistochemical assessments 121 5.2.5 The effect of ADSC-mTG on diabetic osseous defects 123 5.2.5.1 The osteogenic differentiation level of pretreated ADSCs in vitro 123 5.2.5.2 Micro-CT assessments 124 5.2.5.3 Histologic and Immunohistochemical Assessments 125 CHAPTER 6 : DISCUSSION 126 6.1 PROMOTION OF PERIODONTAL REGENERATION BY ORTHODONTIC THERAPY 126 6.1.1 Effect of Orthodontic Movement on Periodontal Regeneration 126 6.1.2 Effect of Orthodontic Onset Timing on Periodontal Regeneration 127 6.1.3 Effect of Direction of Tooth Movement on Periodontal Regeneration 129 6.1.4 Preferable Protocol for Better Clinical Outcomes and other Factors 132 6.1.5 Limitations of our study 135 6.2 ADIPOSE-DERIVED STEM CELLS APPLICATION FOR DIABETIC PERIODONTAL REGENERATION 139 6.2.1 Stem Cell Therapy for Promoting Mucosal Wound Healing 140 6.2.2 Stem Cell Therapy for Promoting Osseous Regeneration 144 6.2.3 Stem Cell Therapy for Diabetes 147 6.2.4 Limitations of our study 150 CHAPTER 7 : CONCLUSIONS 156 TABLES AND FIGURES 157 REFERENCES 182 | - |
| dc.language.iso | en | - |
| dc.subject | 脂肪幹細胞 | zh_TW |
| dc.subject | 糖尿病 | zh_TW |
| dc.subject | 組織工程 | zh_TW |
| dc.subject | 牙周再生手術 | zh_TW |
| dc.subject | 骨再生 | zh_TW |
| dc.subject | 矯正治療 | zh_TW |
| dc.subject | Orthodontics | en |
| dc.subject | Periodontal regeneration | en |
| dc.subject | adipose-derived stem cell | en |
| dc.subject | diabetes | en |
| dc.subject | tissue engineering | en |
| dc.subject | bone regeneration | en |
| dc.title | 矯正治療與脂肪幹細胞促進牙周再生之可行性評估 | zh_TW |
| dc.title | Promotion of Periodontal Regeneration by Orthodontic Therapy and Adipose-Derived Stem Cells Application: A Clinical Retrospective Analysis and A Preclinical Evaluation | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 郭彥彬;王振穎;姚宗珍;鄭乃禎;羅文良 | zh_TW |
| dc.contributor.oralexamcommittee | Yen-Pin Kuo ;Chen-Ying Wang;Tsung-Chen Yao;Nai-Chen Cheng;Wen-Liang Lo | en |
| dc.subject.keyword | 牙周再生手術,矯正治療,脂肪幹細胞,糖尿病,組織工程,骨再生, | zh_TW |
| dc.subject.keyword | Periodontal regeneration,Orthodontics,adipose-derived stem cell,diabetes,tissue engineering,bone regeneration, | en |
| dc.relation.page | 219 | - |
| dc.identifier.doi | 10.6342/NTU202301635 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2023-07-19 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 臨床牙醫學研究所 | - |
| 顯示於系所單位： | 臨床牙醫學研究所 | |
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