臺灣博碩士論文加值系統

人體骨骼會因遭受外力撞擊或隨著年齡老化而產生裂紋、缺損，雖然骨骼具有自主修復缺損部位之能力，然而當缺損尺寸過大時則可能造成癒合不全情形。為解決此問題，可植入骨支架至缺損部位中，使骨細胞藉由骨支架生長成骨組織、骨支架再進而降解達到修復之成效。本研究目的為製備出具有生物相容性、可降解性以及可協助骨缺損修復之芯殼結構人工骨支架。本研究在實驗製程中先將聚乙烯醇(polyvinyl alchol, PVA)纖維以16錠編帶機製成中空管狀編織物，再將此中空管狀編織物之中空處注入氫氧基磷灰石(hydroxyapatite, HA)/明膠/PVA溶液製成芯殼結構人工骨支架。研究中改變編織物之交聯參數、熱處理參數以及HA含量，再藉由表面觀察、孔隙率測試、抗壓強度測試、降解測試、膨潤測試、細胞活性以及動物實驗對芯殼結構人工骨支架之特性進行評估。研究結果顯示11層實心PVA 編織物經戊二醛交聯製得之C-PVA編織物抗壓強度均可提升至20 MPa 以上。進一步以熱處理製得之CT-PVA編織物，熱處理時間10 分鐘時抗壓強度可由23.38 MPa提升至285.92 MPa，然而熱處理時間增加至15 分鐘後則抗壓強度下降至142.33 MPa。HA添加0.4 %至CT-中空編織物所製得之芯殼結構人工骨支架抗壓強度可提升至51.7 MPa，然而當HA添加量增加至0.6%時抗壓強度下降至25.13 MPa，由MTT結果顯示芯殼結構人工骨支架具有生物相容性。動物實驗結果亦顯示以芯殼結構人工骨支架進行骨缺損之修復具有良好效益。

Human bones are subjected to cracks and defects in the presence of an impact force or being aging. Although bones can self-heal the impaired site, the excessive size of the damage may prevent the bone from recovering completely. In order to cope with this difficulty, an implant for the injured part is thus required, and enables the osteocytes to grow bone tissues via the bone scaffolds that can decompose in one day, and ultimately leads to a full recovery. Bone scaffolds are typically made of porous degradable materials that provide the mechanical support during repair and regeneration of damaged or diseased bone.
This study aims to create Core-Shel Structured Artificial Bone Scaffolds with biocompatibility, biodegradation, and heal-promotion. Polyvinyl alchol (PVA) fibers are fabricated into hollow PVA braids by using a braiding machine, and a hydroxyapatite (HA)/gelatin)/PVA mixture is infused into the braids in order to form Core-Shel Structured Artificial Bone Scaffolds. The braids are prepared with different combinations of crosslinking parameters, heat treatment conditions, and HA contents, after which the resulting bone scaffolds are then evaluated for their applications by using surface observation, a porosity test, a compressive strength test, a degradation test, a swelling test, an MTT assay, and an in vivio study.
The compressive strength of PVA braids that are crosslinked with glutaraldehyde can be increased by at least 20MPa. A ten-minute heat treatment results in an increase in the compressive strength of PVA braids that is from 23.38MPa to 285.92MPa. However, when being heat-treated for fifteen minutes, the compressive strength is decreased to 142.33MPa. The bone scaffolds have a compressive strength that is increased to 51.7MPa with the addition of 0.4% HA, and it is then decreased to 25.13MPa with the addition of 0.6% HA. The bone scaffolds are proven to have biocompatibility according to the results of cell viability and alkaline phosphatase activity.

作者簡介與致謝 i
中文摘要 ii
Abstract iii
目錄 v
圖目錄 viii
第一章 緒論 1
1.1 前言 1
1.2 骨骼 1
1.2.1 硬骨組織 1
1.2.1.1 人體骨骼癒合機制 6
1.2.2 骨組織工程材料 9
1.2.2.1 金屬材料 10
1.2.2.2 陶瓷材料 10
1.2.2.3 高分子材料 12
1.2.2.4 複合材料 12
1.2.3 聚乙烯醇 13
1.2.4 明膠 16
1.3 文獻回顧 17
1.4 骨支架材料專利 22
1.5 研究動機 32
1.6 研究目的 34
第二章 原理 36
2.1 轉筒式撚線機加撚原理 36
2.2 編帶機編織原理 38
2.3 冷凍乾燥原理 40
2.4 專有名詞解釋 41
第三章 實驗 42
3.1 實驗總流程與說明 42
3.2 實驗材料與藥品 56
3.3 實驗器材與設備 57
3.4 實驗參數設計 58
3.5 測試與分析方法 59
3.5.1 PVA股線之最大拉伸斷裂強力與伸率測試 59
3.5.2 表面型態分析 59
3.2.2.1 實體顯微鏡觀察 59
3.2.2.2 掃描式電子顯微鏡觀察 59
3.5.3 孔隙率測試 59
3.5.4 抗壓強度測試 60
3.5.5 降解率測試 60
3.5.6 膨潤率測試 60
3.5.7 細胞活性分析 61
3.5.8 動物實驗 61
第四章 結果與討論 66
4.1 T.P.I對PVA股線最大拉伸斷裂強度與伸率之影響 66
4.2 C-PVA編織物表面觀察 69
4.3 C-PVA編織物孔隙率量測 71
4.4 C-PVA編織物抗壓強度測試 73
4.5 C-PVA編織物細胞毒性測試-MTT分析 75
4.6 CT-PVA編織物表面觀察 77
4.7 CT-PVA編織物孔隙度量測 79
4.8 CT-PVA編織物抗壓強度測試 81
4.9 HA/明膠/PVA骨支架型態觀察 84
4.10 HA/明膠/PVA骨支架孔隙率測試 88
4.11 HA/明膠/PVA骨支架抗壓強度測試 90
4.12 HA/明膠/PVA骨支架膨潤測試 93
4.13 HA/明膠/PVA骨支架體外降解測試 95
4.14 HA/明膠/PVA骨支架細胞活性 97
4.15 芯殼結構人工骨支架SEM面觀察 99
4.16 芯殼結構人工骨支架抗壓測試 101
4.17 芯殼結構人工骨支架細胞活性 103
4.18 動物實驗 106
4.19 足跡分析 109
4.20 組織切片 113
4.21 本研究成果可應用之醫材用途 122
第五章 結論 123
第六章建議 125
參考文獻 127