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論文名稱 Title |
3D列印技術輔助生物廢棄物合成之磁性奈米透輝石生物陶瓷於骨再生及磁熱療之應用 3D Printing Technology-Assisted Magnetic Nano-Diopside Bioceramics Synthesized from Biowaste for Bone Regeneration and Magnetic Hyperthermia Applications |
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系所名稱 Department |
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畢業學年期 Year, semester |
語文別 Language |
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學位類別 Degree |
頁數 Number of pages |
129 |
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研究生 Author |
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指導教授 Advisor |
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召集委員 Convenor |
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口試委員 Advisory Committee |
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口試日期 Date of Exam |
2024-01-05 |
繳交日期 Date of Submission |
2024-01-10 |
關鍵字 Keywords |
生物廢棄物、透輝石、磁性奈米顆粒、3D列印支架、骨再生、磁熱療、多功能生醫材料 Biowaste, Diopside, Magnetic nanoparticles, 3D printing scaffold, Bone regeneration, Magnetic hyperthermia, Multifunctional biomaterials |
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統計 Statistics |
本論文已被瀏覽 150 次,被下載 0 次 The thesis/dissertation has been browsed 150 times, has been downloaded 0 times. |
中文摘要 |
目前骨腫瘤引起缺損的同步治療和再生仍是一大挑戰,手術後植入骨移植材料的傳統治療策略雖然可以使術後骨缺損再生,卻無法完全去除殘餘的腫瘤細胞。為了克服以上問題,生物醫學領域一直在尋求新的技術和方法來改進治療和修復的能力,尤其在骨再生和癌症治療方面。此外,磁性奈米材料的加入也為生物醫學研究和治療領域開闢一條新的前景,特別是在磁熱療法方面上。與單純的生物陶瓷材料相比,磁性複合生物陶瓷在於優化熱療的能力上備受矚目,因此開發滿足骨組織工程和骨肉瘤治療需求的多功能複合生醫材料為近期研究的重點。同時,隨著材料科學和工程技術的不斷進步,3D列印技術已成為生物醫學領域中的一項突破性工具,為社會帶來前所未有的機會,進而得以重新定義骨組織工程和治療方法。 本研究之主要目的在為骨再生治療和癌症治療領域帶來創新,同時強調了資源的可持續性。首先透過對生物廢棄物合成透輝石生物陶瓷與磁性奈米顆粒深入的研究和實驗驗證,隨後結合3D列印技術的應用,期望為生物醫學領域提供新的可能性,進而提高患者的生活品質和治療效果。 本實驗主要透過球磨法合成透輝石並添加水熱法合成的MnFe2O4磁性奈米顆粒製備出Diopside-MnFe2O4生物陶瓷。透過對材料的分析、體外生物實驗以及磁熱療的效果評估,挑選出最有潛力的Diopside-MnFe2O4比例 (100:0、90:10、80:20、70:30) ,並利用DLP 3D列印技術製備出支架,以進一步進行材料分析、體外生物實驗、磁熱療、人體模擬液 (SBF) 浸泡測試以及體外動物實驗,能更完整的分析出支架對骨再生以及磁熱療應用的潛力。 Diopside-MnFe2O4生物陶瓷的ESEM結果顯示添加MnFe2O4磁性奈米顆粒使透輝石生物陶瓷緻密化,提升了材料的密度和硬度。體外生物測試中,Di-10MnFe及Di-20MnFe表現出良好的生物相容性和成骨分化能力。磁熱療能力測試顯示所有樣品均具有可控的磁熱療效果,其中Di-10MnFe具有長達10分鐘以上的熱療效果且未超過 46℃ ,被選為後續研究的主要材料。該材料結合了DLP 3D列印技術進行更深入的骨再生和磁熱療研究。在研究中,Di-10MnFe列印支架具備多孔結構,包含大於300 μm的孔隙、小於50μm的微孔,孔隙率高達58.7%。機械性質實驗顯示Di-10MnFe 3D列印支架在浸泡SBF前後抗壓強度維持在2.84-6.23 MPa,符合人體鬆質骨的抗壓強度範圍 (2-13MPa) 。Di-10MnFe列印支架在鹼性磷酸酶活性 (ALP) 實驗中促進成骨細胞分化,並在茜素紅 (ARS) 染色結果展現礦化潛力。在磁熱療抑制癌細胞實驗中,Di-10MnFe列印支架呈現可控的磁熱療效果,對癌細胞顯著抑制並不會對健康骨細胞產生影響,證實其應用性和安全性。在SBF浸泡測試中,支架表面形成奈米級磷灰石沉積,維持穩定的中性pH值。動物實驗顯示支架植入大鼠體內無毒性,促進骨骼增長,且具成骨再生潛力。 本研究之最佳化Di-10MnFe支架可望成為骨再生治療和癌症治療的新選擇,具多功能應用。進一步研究聚焦於3D列印技術的優化、可持續性材料的開發,以及臨床實驗,以確保其安全性和實際應用效果。 |
Abstract |
Currently, synchronous therapy and regeneration for bone defects caused by tumors remain significant challenges. Traditional strategies involving implantation of bone graft materials post-surgery promote bone regeneration but fail to completely eliminate residual tumor cells. The biomedical field continually seeks innovative techniques, especially in bone regeneration and cancer treatment. The incorporation and application of magnetic nanomaterials present a new frontier in biomedical research and therapy, particularly in magnetic hyperthermia. Compared to simple bioceramic materials, the attention is focused on the enhanced hyperthermia capabilities of magnetic composite bioceramics, addressing the needs of bone tissue engineering and osteosarcoma treatment. Simultaneously, with advancements in material science and engineering, 3D printing has emerged as a groundbreaking tool in the biomedical field, offering unprecedented opportunities to redefine tissue engineering and therapeutic approaches. The primary objective of this study is to bring innovation to the fields of bone regeneration therapy and cancer treatment while emphasizing resource sustainability. Through in-depth research and experimentation involving the synthesis of diopside bioceramics and magnetic nanoparticles from biological waste, coupled with the application of 3D printing technology, we aim to provide new possibilities for the biomedical field, enhancing both patient quality of life and treatment outcomes. The experimental approach involves the synthesis of diopside through ball milling, followed by the hydrothermal synthesis of MnFe2O4 magnetic nanoparticles. This combination results in the preparation of diopside- MnFe2O4 bioceramics. Material analysis, in vitro biological experiments, and evaluation of magnetic hyperthermia effects will be conducted to identify the most promising diopside- MnFe2O4 composition. Subsequently, Digital Light Processing (DLP) 3D printing technology will be applied to fabricate the Di-10MnFe 3D printing scaffold. Further analyses of the material, in vitro biological experiments, magnetic hyperthermia inhibition of cancer cells, immersion testing in simulated body fluid (SBF), and in vitro animal experiments will comprehensively assess the potential of the Di-10MnFe 3D printing scaffold for bone regeneration and magnetic hyperthermia applications. Environmental scanning electron microscope (ESEM) results for the Diopside- MnFe2O4 bioceramics demonstrate enhanced density and hardness due to the addition of MnFe2O4 magnetic nanoparticles. In vitro biological tests show good biocompatibility and osteogenic differentiation capabilities for Di-10MnFe and Di-20MnFe. Magnetic hyperthermia tests reveal controllable thermal effects for all samples, with Di-10MnFe exhibiting thermal effects lasting over 10 minutes without exceeding 46°C, making it the primary material for subsequent research. This material will be combined with DLP 3D printing technology for more in-depth studies on bone regeneration and magnetic hyperthermia. The successful synthesis of the Di-10MnFe 3D printing scaffold, featuring a porous structure with pore sizes larger than 300μm and micropores smaller than 50μm, and a porosity rate of 58.7%, was achieved. Mechanical property experiments show that Di-10MnFe 3D printing scaffold maintains compressive strength between 2.84-6.23 MPa before and after immersion in SBF, within the compressive strength range of human trabecular bone (2-12MPa) . In alkaline phosphatase (ALP) experiments, Di-10MnFe promotes osteogenic cell differentiation, and Alizarin Red S (ARS) staining demonstrates mineralization potential. In magnetic hyperthermia inhibition of cancer cell experiments, Di-10MnFe 3D printing scaffold exhibits controllable magnetic hyperthermia effects, significantly suppressing cancer cells without affecting healthy bone cells, confirming its applicability and safety. In SBF immersion tests, the scaffold surface forms nano-sized hydroxyapatite deposits, maintaining a stable neutral pH value. Animal experiments demonstrate the scaffold was non-cytotoxic when implanted into rats, promoting bone growth and showing potential for bone regeneration. The Di-10MnFe 3D printing scaffold from this study holds promise as a novel choice for bone regeneration therapy and cancer treatment, with multifunctional applications. Future research will focus on optimizing 3D printing technology, developing sustainable materials, and conducting clinical trials to ensure safety and practical application effectiveness. |
目次 Table of Contents |
論文審定書 i 誌謝 ii 摘要 iii Abstract v 目錄 viii 圖次 xi 表次 xiv 第一章緒論1 1.1 前言1 1.2 研究動機2 1.3 研究目的3 1.4 論文架構4 第二章文獻回顧與理論基礎5 2.1 人體骨骼組織簡介5 2.2 骨植入物簡介及分類8 2.3 生物陶瓷-透輝石(CaMgSi2O6)10 2.4 生物廢棄物之可續性及其再生利用12 2.5 磁奈米顆粒特性與應用13 2.6 磁熱療機制16 2.7 3D列印技術於生物陶瓷的應用18 第三章研究方法23 3.1 實驗架構23 3.2 實驗藥品及材料25 3.3 實驗流程與材料製備28 3.4 生物3D列印技術開發-數位光固化處理(DLP)30 3.5 實驗儀器32 3.6 分析儀器與材料表徵34 3.7 體外生物實驗44 3.8 體外磁熱療放熱分析49 3.9 人體模擬液 (SBF) 浸泡測試52 3.10 動物實驗54 3.11 統計分析55 第四章結果與討論56 4.1 初始材料分析56 4.2 Diopside-MnFe2O4生物陶瓷材料分析62 4.3 Diopside-MnFe2O4生物陶瓷體外生物測試67 4.4 Diopside-MnFe2O4生物陶瓷磁熱療能力評估71 4.5 Di-10MnFe 3D列印支架材料分析75 4.6 Di-10MnFe 3D列印支架體外生物測試80 4.7 Di-10MnFe 3D列印支架磁熱療能力評估85 4.8 Di-10MnFe 3D列印支架人體模擬液浸泡測試90 4.9 Di-10MnFe 3D列印支架動物實驗94 第五章結論與未來展望97 5.1 結論97 5.2 未來展望100 參考文獻101 |
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