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研究生:林柏良
研究生(外文):Po-Liang Lin
論文名稱:以生物可分解聚乳酸為基材之複合材料系統之植入物與生物支架之研發
論文名稱(外文):The research and development of biodegradable polylactic acid based composite materials for implant and scaffold applications
指導教授:方旭偉方旭偉引用關係
指導教授(外文):Hsu-Wei Fang
口試委員:張文忠張印本張至宏姚俊旭汪昆立黃聲東
口試委員(外文):Wen-Chung ChangYin-Pen ChangChih-Hung ChangChun-Hsu YaoKun-Li WangSheng-Tung Huang
口試日期:2012-01-31
學位類別:博士
校院名稱:國立臺北科技大學
系所名稱:工程科技研究所
學門:工程學門
學類:材料工程學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:英文
論文頁數:88
中文關鍵詞:聚乳酸氫氧基磷灰石三鈣磷酸鹽聚丙烯碳酸酯生物可分解性生物相容性彈性
外文關鍵詞:polylactic acidhydroxyapatitetri-calcium phosphatepolypropylene carbonatebiodegradablebiocompatibleflexible
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聚乳酸因為其生物可分解性、生物可吸收性及生物相容性的性質,已經被廣泛的運用在生物醫學上。如骨釘、骨板、可吸收手術縫合線及骨填補支架。然而因為其無法獨立控制的問題,如若需要骨釘則機械強度就要高,聚乳酸分子量就會大,那麼其分解速率就會相對的變慢。
因此,如何獨立控制聚乳酸的機械強度及分解速率就是我們要研究的課題。文獻上指出聚乳酸加入氫氧基磷灰石或三鈣磷酸鹽有助於骨母細胞的生長;而加入聚丙烯碳酸酯則是可以降低其玻璃轉移溫度(Tg),使得材料變得較有彈性。
在本研究中,我們將利用溶劑混合法及鹽析法將氫氧基磷灰石、三鈣磷酸鹽或聚丙烯碳酸酯與聚乳酸混合去研發出以聚乳酸為基材的複合材料。而研究結果顯示出,我們因為氫氧基磷灰石、三鈣磷酸鹽或聚丙烯碳酸酯的含量不同,其機械性質與分解速率也有顯著的不同,這證明了我們可以獨立控制聚乳酸複合材料的機械性質與分解速率;我們也利用鹽析法成功的研發出無溶劑殘留的多孔性聚乳酸複合材料;最後我們使得聚乳酸複合材料具有較高的彈性度,並在室溫下我們就可以像橡皮擦一樣的任意改變其形狀;而臨床前動物試驗的結果也顯示出聚乳酸複合材料的生物相容性及有助於骨母細胞生長的特性。此研究成果讓幫助我們找出聚乳酸複合材料對於特定醫學應用上配方的最佳化,而這也有助於我們將來在聚乳酸複合材料商品化的推廣。

Polylactic acid (PLA) materials have been used in biomedical applications such as bone screws, sutures, and scaffold materials because they are biodegradable, bioresorbable, and biocompatible. There is an increasing need to achieve independent control of key properties such as mechanical strength, degradation rate, and bioactivity in order to further enhance the performance of PLA-based medical implants.
Because PLA composites containing hydroxyapatite (HAp) or tricalcium phosphate (TCP) particles can augment cell growth and mechanical properties, PLA composites containing polypropylene carbonate (PPC) can decrease the value of the glass transition temperature Tg, which makes the PLA composites flexible.
Hence, in this study, we use a solvent mix method and a non-solvent salt leaching method to fabricate PLA-based composite materials with hydroxyapatite (HAp), tricalcium phosphate (TCP), or polypropylene carbonate (PPC). The resultant properties of the PLA-based composite materials show that we can control the mechanical properties and degradation rate of these materials independently, turn them into porous composites, make them relatively elastic, and change their shape at room temperature; one example of such a material is an eraser. A pre-clinical study (animal study) proves the biocompatibility of PLA composite materials. This can help us to promote the commercialization of PLA composite materials quickly. The information resulting from this study can assist in the optimization of PLA composite formulas for specific medical applications.

摘 要…………………………………………………………………i
ABSTRACT……………………………………………………………iii
ACKNOWLEDGEMENT……………………………………………………v
CONTENTS………………………………………………………………vi
EQUATION CONTENTS……………………………………………………………ix
TABLE CONTENTS……………………………………………………x
FIGURE CONTENTS………………………………………………………………xi
Chapter 1 INTRODUCTION…………………………………………………………1
Chapter 2 BACKGROUND…………………………………………………………5
2.1 Types of bone graft material……………………………5
2.1.1 Metals and alloys………………………………………6
2.1.2 Ceramic materials………………………………………6
2.1.3 Polymer materials……………………………………7
2.2 Polylactic acid (PLA) ………………………………7
2.3 Ceramics and co-polymer………………………………11
2.3.1 Hydroxyapatite (HAp) ………………………………11
2.3.2 Tricalcium phosphate (TCP) ………………………12
2.3.2 Polypropylene carbonate (PPC) ……………………13
2.4 Methods for artificial bone graft preparation……14
2.4.1 Solvent blending method……………………………15
2.4.2 Salt leaching method…………………………………17
Chapter 3 MATERIALS AND EXPERIMENT METHODS……………18
3.1 Preparation of PDLLA/HAp composite…………………18
3.2 Fabrication of PDLLA/TCP porous scaffold………………19
3.3 Preparation of PPC/TCP, PPC/PDLLA, and PPC/PDLLA/TCP elastic composites…………………………………………………21
3.4 Preparation of PPC/PDLLA/TCP porous scaffold…………22
3.5 Mechanical testing……………………………………………23
3.5.1 Compression mechanical test……………………………23
3.5.2 Bending mechanical test…………………………………24
3.5.3 Tensile mechanical test………………………………25
3.6 In-vitro degradation…………………………………………25
3.7 Cell proliferation study……………………………………26
3.8 Cell proliferation analysis………………………………27
3.9 In-vivo study…………………………………………………28
3.10 Biocompatibility test……………………………………29
3.10.1 Pyrogen test……………………………………………29
3.10.2 Skin irritation test…………………………………30
Chapter 4 EFFECTS OF HAP DOSAGE ON PDLLA COMPOSITES MATERIALS 31
4.1 Materials morphology……………………………………31
4.2 Mechanical properties…………………………………32
4.3. Degradation behavior……………………………………37
4.4 Osteoblast proliferation……………………………………39
Chapter 5 A NON-SOLVENT SALT LEACHED PROCESS TO PREPARE PDLLA/TCP POROUS SCAFFOLD………………………………………42
5.1 PDLLA/TCP porous scaffold morphology…………………42
5.2 Mechanical properties………………………………………44
5.3 Osteoblast proliferation…………………………………46
5.4 Histology analysis…………………………………………47
Chapter 6 EFFECTS OF PDLLA AND TCP DOSAGE ON PPC COMPOSITE MATERIALS…………………………………………………………53
6.1 DSC result…………………………………………………53
6.2 PPC/PDLLA/TCP porous scaffold morphology…………54
6.3 Mechanical properties…………………………………55
6.4 In-vitro degradation behavior…………………………63
6.5 Osteoblast proliferation…………………………………64
6.6 Biocompatibility test……………………………………65
Chapter 7 CONCLUSIONS……………………………………………67
REFERENCES…………………………………………………………70
Appendix A: CHEMICALS…………………………………………77
Appendix B: DEVICES……………………………………………78
Appendix C: LIMULUS AMEBOCYTE LYSATE (LAL) TEST………80
Appendix D: SKIN IRRITATION TEST PROCESS………………82
Appendix E: PUBLICATIONS……………………………………84


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