近期研究指出褐藻多醣 (Fucoidan, F) 可提升骨修復相關基因表現量，氫氧基磷灰石 (Hydroxyapatite, HAP) 則為常見的骨修復材料，研究顯示氫氧基磷灰石表面電荷、顆粒大小與型態均會影響顆粒與細胞之相容性，因此本報告將奈米與微米氫氧基磷灰石改變表面電荷，與帶負電的褐藻多醣結合形成複合物，但此複合物僅具骨傳導功能，因此再攜帶具有骨誘導特性之褪黑激素，探討改質後之複合物對於骨組織再生之影響。奈米氫氧基磷灰石單體的粒徑約為 20-30 nm，微米氫氧基磷灰石的粒徑約為 5 μm，利用傅立葉轉換紅外線光譜儀及 Ninhydrin 試驗證實成功將 12-aminododecanoic acid 嫁接至氫氧基磷灰石表面，並可利用元素分析儀得知改質後氫氧基磷灰石-褐藻多醣複合物奈米與微米之褐藻多醣之嫁接量，分別為 7 μg/mg 與 15 μg/mg，X 射線分析儀顯示改質後並不會改變晶體結構及成功攜帶褪黑激素。將複合物以濃度 1 mg/mL 與小鼠成骨前驅細胞共培養，結果顯示複合物與細胞具有良好相容性，改質後氫氧基磷灰石-褐藻多醣複合物奈米與微米的組別，加入褐藻多醣後能提升鹼性磷酸酶活性，其中以微米的組別活性較高，改質後氫氧基磷灰石-褐藻多醣攜帶褪黑激素之複合物，藉由釋放褪黑激素能顯著提升鹼性磷酸酶活性，並達到提前礦化的作用，縮短成骨細胞分化時間。綜合上述成功改質氫氧基磷灰石並攜帶褐藻多醣及褪黑激素，且複合物為良好的骨修復材料。

Recent reports have revealed that fucoidan has osteoconductive property, which can elevate osteoblast-related gene expressions. Another well-known candidate for bone tissue engineering applications is hydroxyapatite (HAP). The characteristics of hydroxyapatite, including size, shape, and surface charge, are the primary parameters for cellular uptake. Therefore, the aim of this study is surface modification of hydroxyapatite nanoparticles (n-HAP-N) and hydroxyapatite microparticles (μ-HAP-N) to combine with fucoidan, and then to encapsulate melatonin for evaluating its effect on differentiation of murine osteoblast-like cell line (MC3T3-E1). Hydroxyapatite nanoparticles and microparticles were 20 nm and 5 μm. in the diameter. Fourier-transform infrared spectrometer (FT-IR) and Ninhydrin test were used to confirmed the adsorption and binding of the 12-aminododecanoic acid on the HAP surfaces. Elemental analyzer calculated fucoidan grafting content of nano and micro hydroxyapatite- fucoidan complexes (HAP-N-F), which were 7 μg/mg and 15 μg/mg. X-ray diffraction (XRD) revealed that surface modifications did not change the crystal structure of HAP and successfully encapsulate melatonin. Complexes with dosage 1 mg/mL co-cultured with pre-osteoblast cells showed good biocompatibility. The results showed that added fucoidan to n-HAP-N and μ-HAP-N can enhance alkaline phosphatase (ALP), among which μ-HAP-N-F showed greater ALP activity. Melatonin-loaded hydroxyapatite-fucoidan complexes (HAP-N-F/M) can increased ALP activity and enhanced calcium deposit by releasing melatonin. In summary, melatonin-loaded hydroxyapatite-fucoidan complexes were successfully synthesized and could be a potential candidate for bone-tissue engineering applications.

摘要 I
Abstract II
目錄 i
圖目錄 ii
表目錄 iii
第一章、前言 1
第二章、文獻回顧 3
2.1 牙周缺陷成因 3
2.2 牙周組織再生工程 3
2.3 褐藻多醣 5
2.4 氫氧基磷灰石 6
2.5 褪黑激素 8
第三章、實驗動機與目的 9
第四章、實驗架構 10
第五章、實驗流程 11
第六章、實驗材料與方法 12
6.1 實驗材料 12
6.2 實驗藥品 12
6.3 實驗儀器 13
6.4 實驗溶液配置 15
6.5 實驗方法 16
第七章、實驗結果與討論 21
7.1 奈米和微米氫氧基磷灰石 (HAP) 之鑑定 21
7.2 改質後之氫氧基磷灰石 (HAP-N) 之鑑定 22
7.3 褐藻多醣成分分析 23
7.4 改質後之氫氧基磷灰石-褐藻多醣複合物 (HAP-N-F) 之鑑定 23
7.5 改質後之氫氧基磷灰石-褐藻多醣複合物攜帶褪黑激素 (HAP-N-F/M) 之鑑定 24
7.6 複合物對於小鼠成骨前驅細胞之影響 25
第八章、結論 28
第九章、參考文獻 29
第十章、圖表 38
第十一、附錄 66

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