植體周圍炎是造成晚期植牙失敗的主要風險之一，由於生物膜附著於鈦金屬表面，傳統藥物治療通常無法完全清除致病菌。在本研究中，我們發展出攜帶四環黴素（tetracycline）的奈米級缺鈣型氫氧基磷灰石（calcium-deficient hydroxyapatite）希望能達到生物膜的去除、刺激齒槽骨再生並運用於植體周圍炎的治療。
針對裝載四環黴素的缺鈣型氫氧基磷灰石奈米粒子（TC-CDHA），我先以掃描式電子顯微鏡（SEM）、穿透式電子顯微鏡、（TEM）、X光繞射（XRD）、能量散佈分析儀（EDS）以及動態光散射（DLS）來檢定性質，接著再測定其最低抑菌濃度（MIC）和最低殺菌濃度（MBC）以評估TC-CDHA對於致病菌的抗菌能力。
在掃描式電子顯微鏡和穿透式電子顯微鏡下，TC-CDHA呈現小於100奈米之柱狀型態，其結晶大小經過謝樂公式（Scherrer’s formula）計算約為10.8奈米長4.62奈米寬之構型。我們進一步發現四環黴素裝載至缺鈣型氫氧基磷灰石奈米載體，其藥物裝載率經測試為86.23%，在能量散佈分析儀的檢測下發現四環黴素能與缺鈣型氫氧基磷灰石複合。在同為0.1微克/毫升的藥物濃度下，抗菌檢定顯示裝載抗生素的奈米粒子（89.47%）與自由形式的四環黴素（86.25%）有著相近的50%抑菌濃度。
本研究顯示TC-CDHA有著與自由態TC相近的抗菌能力，並且由於缺鈣氫氧基磷灰石可能具有刺激骨再生的潛力，而有機會運用於未來植體周圍炎的治療。

Peri-implantits is a major risk factor for late dental implants failures. Traditional remedy usually failed to eliminate pathogens completely due to biofilm covering the titanium surface. In this study, we developed a nano calcium-deficient hydroxyapatite (CDHA) carrier intended for extended tetracycline (TC) release to disrupt biofilm on the implant surface while simultaneously enhance new bone regeneration for peri-implantitis treatment. The tetracycline-loaded CDHA nanoparticles (TC-CDHA) were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and dynamic light scattering (DLS). The TC-CDHAs were then evaluated for anti-bacteria potency by determine their minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) of pathogens. The TC-CDHA presented as round, less than 100nm rod shape particles under SEM and TEM. The crystalline size measured by Scherrer’s formula is about 10.8nm x 4.62nm. We discovered that the loading capacity of TC was 86.23%. Tetracycline is well embedded in the CDHA as revealed by EDS examination. Anti-bacterial assay showed that the MIC of the drug loaded nanoparticles are comparable to that of the freeform TC (86.25% for TC vs. 89.47% for TC-CDHA) when both were at TC concentration of 0.1ug/ml. This study revealed that the as prepared TC-CDHA has similar potency as freeform TC while may harbor additional advantages for stimulating bone regeneration. Such nanomedicine holds a promising future for peri-implantitis treatment.

中文摘要………………………………………………………………………………..I
Abstract………………………………………………………………………………..II
致謝……………………………………………………………………………….. III
Content ………………………………………………………………………………..IV
List of tables ………………………………………………………………………………..VII
List of figures……………………………………………………………………………….. VIII
Abbreviations ………………………………………………………………………………..IX
1. Introduction………………………………………………………………………………..1
1.1. Peri-implantitis………………………………………………….………………………1
1.1.1. Etiology and Pathogenesis…………………………………………………………1
1.1.2. Microbiota and Biofilm………………………………….………………………2
1.2. Peri-implantitis clinical management……………………………………………………4
1.2.1. Mechanical therapy and Chemotherapy…………………...……………………..4
1.2.2. Current recommended treatment logistics………………………………………..5
1.3. Common materials for peri-implantitis management……………………………………6
1.3.1. Ceramic scaffold materials……………………………………...………………..6
1.4. Considerations for future advanced peri-implantitis therapeutics……….………………8
1.4.1. Infection control………………………………………………………………….8
1.4.2. Tissue regeneration……………………………………………………………….9
1.5. Motivation and aims…………………………………………………………..…………9
2. Materials and methods…………………………………………………………...………11
2.1. Preparation of CDHA and particle size analysis…………………………..…….11
2.2. Loading tetracycline to CDHA………………………………...…………..……12
2.3. Characterization of CDHA……………………………………………………….12
2.3.1. Dynamic light scattering (DLS) …………………………………………….12
2.3.2. X-ray Diffraction (XRD)…………………………………………………..13
2.3.3. Scanning Electron Microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS)………………………………………….…………………..…………13
2.3.4. Transmission electron microscope (TEM) .....................……………………...14
2.4. Evaluation of the anti-bacteria potency of the nanoparticles to pathogens …..…..….14
2.4.1. Minimum inhibitory concentration (MIC) ……………………………………….14
2.4.2. Minimum bactericide concentration (MBC)…………………………………..…15
2.5. Statistical analysis……………………………………………………………………15
3. Results……………………………………………………………………………………16
3.1. Characterization of CDHA………………………………………………………16
3.1.1. Dynamic light scattering (DLS)……………………………………………16
3.1.2. X-ray Diffraction (XRD)………………………………………………….16
3.1.3. Scanning Electron Microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS)……………………………………………………………………………17
3.1.4. Transmission electron microscope (TEM) ………………………………..18
3.2. Evaluation of the anti-bacteria potency of the nanoparticles to pathogens …………...18
3.2.1. Minimum inhibitory concentration (MIC) and Minimum bactericide concentration (MBC)………………………………………..…………………………………18
4. Discussions……………………………………………………………………………….19
5. Conclusion…………………………………………………………………………..……23
6. Reference…………………………………………………………………………………24
7. Tables…………………………………………………………………………………….29
8. Figures and legends………………………………………………………………………33

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