臺灣博碩士論文加值系統

具有骨傳導性的植入物可促進骨缺損修復。臨床常見的骨缺損常發生於嚴重創傷、腫瘤、感染或是先天性的肌肉骨骼疾病之併發症。組織中若有骨組織缺損，植入具有骨缺損修復的材料，促進骨組織再生是不可缺少的治療行為。評估開發促進骨缺損組織修復之生醫材料是否合適，需要建立臨床相關的體外與體內評估的模型，研究材料的生物相容性、力學性質、降解以及生醫材料在動物組織內相互關係。臨床上有許多具有良好生物相容性、優異的力學強度、材料可降解、低毒性等生醫材料應用。隨著此議題的愈加深入的探討，許多骨填補材料的臨床應用亦被廣泛的發想，同時也有許多的材料被應用於骨組織修復上。
在臨床應用經驗上，使用骨水泥或是填充骨粉修復骨缺損部位是常用的方法，但在使用骨水泥填補過程中，將有放熱反應存在可能傷及骨周邊組織的潛在風險；而使用以粉末狀的骨填補材料進行填補也有機械強度不足的問題，需要以骨釘或是骨板進行輔助，增加臨床應用的複雜度。本研究即是考量臨床實用性下進行以常溫下易塑型，易切削，具有一定機械強度且為多孔性可分解材料作為新型骨填補材料實驗設計。在本研究中，透過設計一種新型且具有彈性多孔複合材料，結合聚碳酸丙烯酯（PPC），聚乳酸（PDLA）和磷酸鈣（β-TCP）等材料特性，作為骨傳導支架。並且使用鹽析法作為一種複合材料簡易造孔的無溶劑操作法。透過體外與體內評估進行材料功能性檢測，機械性質測試，研究此新型材料的生物相容性、力學性質、降解性質。
　　由動物實驗模型結果顯示以PPC / PDLA / TCP重量比為90/8/2製備的PPTE多孔支架是（1）具有生物相容性的，透過細胞培養研究並在動物體內產生最小的炎症反應; （2）具有延展性，使得支架可以容易地填補到骨缺損中而不破裂;和（3）PPTE多孔支架具生物降解性以及且骨傳導性的，可促進新骨向骨缺損修復漸進形成。本材料也可以與PRP膠進行結合，使得此新型骨填補材料兼具骨傳導性以及骨誘導性，可以促進缺損骨組織癒合。實驗結果表明，本研究所開發的新型支架與骨誘導劑如PRP膠，骨形態發生蛋白，脫礦骨基質或間質細胞的組合用於修復骨缺損將具有成為新型臨床應用生物材料的潛力。

An osteoconductive scaffold can facilitate bone defect repair. Bone defects are serious complications that are most commonly caused by extensive trauma, tumors, infections, or congenital musculoskeletal disorders. If nonunion occurs, the implantation of biomaterials developed as a bone defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials for potential development as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models to investigate their biocompatibility, mechanical properties, degradation, and interactions with the culture medium or host tissues. In clinical practice, the treatment of bone defect would commonly use bone cement or bone graft with powder. However, the exothermic reaction would at the potential risk of injuring harm to the outside organization while filling bone cement. Instead of the use of powdered bone-filling materials also has the issue of insufficient mechanical strength which would be assisted with some bone screws or bone plates that made the clinical applications much more complexity. In this study, a novel elastic porous composite comprising poly(propylene carbonate) (PPC), poly(D-lactic acid) (PDLA), and β-tricalcium phosphate (β-TCP) was prepared as an osteoconductive scaffold. A salt-leaching method is a nonsolvent and easily operated method used to mold up the porous scaffolds.
　　The novel malleable composite scaffolds composed of PPC/PDLA/TCP were evaluated as bone substitutes for bone defect repair. The animal model results demonstrated that a PPTE porous scaffold made with a PPC/PDLA/TCP weight ratio of 90/8/2 is (1) biocompatible, yielding a positive cell culture study and minimal inflammatory response in vivo; (2) malleable, such that the scaffold can be molded into the bone defect easily without fracturing; and (3) biodegradable and osteoconductive, promoting the progressive formation of new bone into the bone defect. These results indicated that the combination of this scaffold with osteoinductive agents, such as bone morphogenetic protein, demineralized bone matrix, or mesenchymal cells, might generate new biomaterial for bone defect repair.

摘　要 i
ABSTRACT iii
致謝 v
CONTENTS vi
TABLE CONTENTS vii
FIGURE CONTENTS viii
Chapter 1 Introduction 1
Chapter 2 Background 5
2.1 Historical perspective of polymer as a bone implantable material 5
2.2 In vitro and functional testing of biodegradable polymers for bone implants 15
2.3 In vivo testing of biodegradable polymers for bone implants 19
Chapter 3 Materials and experiment methods 23
3.1 Materials 23
3.2 Preparation of porous PPC/PDLLA/β-TCP scaffolds 24
3.3 Mechanical testing 27
3.4 Cell culturing 28
3.5 Bioactivity analysis 28
3.6 Preparation of rabbit PRP and PRP gel 32
Chapter 4 Effects of polymer scaffolds under in vitro testing 34
4.1 Mechanical properties of polymer composites 34
4.2 Porous β-TCP/PPC/PDLLA scaffolds 39
4.3 Measurement of the water contact angle 43
4.4 PPTE composite encouraged adhesion of mouse osteoblasts 47
4.5 Discussion 54
4.6 Conclusion 57
Chapter 5 Effects of polymer scaffolds in animal model 59
5.1 Surgical procedures 62
5.2 Micro-computed-tomography analysis 67
5.3 Histological evaluations 73
Chapter 6 Conclusions 77
References 79

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