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研究生(外文):Wei-Hong Deng
論文名稱(外文):Development and Biomechanical Testing of Hydrogels for Artificial Nucleus
指導教授(外文):Weng-Pin Chen
外文關鍵詞:Degenerative disc diseasenucleus pulposus replacementhydrogelhydrogel implantscompression testcreep test
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椎間盤退化性病症是一項常見的疾病,會導致病變椎間盤周圍組織產生發炎與不穩定等現象。若其症狀須進行外科手術治療時,最常使用的治療方式為脊椎融合術。儘管成功的融合在臨床上可能是一種理想的短期解決方式,但是由於脊椎的融合可能與鄰近椎節椎間盤加速退化或其他併發症有關。因此,非融合手術成為治療椎間盤退化病症的另一項選擇。其中人工髓核置換術屬於非融合手術技術,可維持椎節的活動度與功能特性,並避免對鄰近椎節造成傷害;然而,此技術目前處於初期發展階段,亦持續有新的材料被開發應用於髓核置換裝置。因此,本研究目的是開發玻尿酸與蠶絲蛋白合成之複合水凝膠,並驗證此複合水凝膠是否具備與豬隻髓核相似之生物力學特性以及評估複合水凝膠植入椎間盤之可行性。複合水凝膠與豬腰椎髓核在拘束壓縮測試中,利用應力-應變曲線圖計算5%應變量下的壓縮模數(E=σ/ε),結果顯示複合水凝膠比豬腰椎髓核之壓縮模數有略小的趨勢,但在統計分析下彼此沒有顯著性差異,證明複合水凝膠有相似於豬腰椎髓核之力學特性。複合水凝膠植入椎間盤壓縮破壞測試,利用力量-位移曲線紀錄完整組、骨移除組、植入組壓縮破壞時的極限力量與極限位移量,並計算極限勁度,結果顯示複合水凝膠植入後能提升椎間盤的極限勁度,且在統計分析下與完整組沒有顯著性差異,代表複合水凝膠植入椎間盤後能提升及恢復與完整組相似的極限強度。複合水凝膠植入椎間盤壓縮破壞測試也探討了15% 應量(0.9 mm)下的壓縮勁度,從結果得知複合水凝膠植入椎間盤後有增加椎間盤強度之趨勢,壓縮勁度也會隨著應變量的增加而增加,呈現非線性的曲線,代表著複合水凝膠植入椎間盤後具有黏彈特性。複合水凝膠植入椎間盤潛變測試,紀錄固定壓力下之位移與時間的關係曲線,並套入雙相線性數學模型得到雙相材料特性(HA、K0),在結果顯示,複合水凝膠植入椎間盤後能提升椎間盤聚合模數(HA)之趨勢,且恢復與完整組相似的滲透率在統計分析下沒有顯著性差異,證明複合水凝膠植入椎間盤的可行性。從本研究測試結果評估後,此款複合水凝膠具有未來應用於人工髓核置換術之可行性。
Degenerative disc disease (DDD) is one of the most common diseases resulting from inflammation and instability around the affected spinal disc. Spinal fusion is the most commonly performed procedure to treat DDD if surgical intervention is deemed necessary. Successful fusion can be a desirable short-term solution; however, spinal fusion is associated with the accelerated degeneration of adjacent discs and an uncertain outcome. Accordingly, a non-fusion surgery is an alternative strategy to fusion in the treatment of patients with DDD. Nucleus pulposus replacement (NR) is a non-fusion surgical technique that holds the prospect of not compromising either mobility or function and causing no adjacent-level injury; however, this technique is still in the early stages, and new materials for the NR devices are still under development. Therefore, the objective of this study is to develop a silk fibroin/hyaluronic acid (SF/HA) composite hydrogel and to demonstrate scientifically whether its biomechanical behavior is similar to that of porcine nucleus pulposus and to assess the feasibility of the composite hydrogels when implanted into the disc. Confined compression tests for the composite hydrogel and porcine natural nucleus pulposus were perfomed, the stress - strain curves were used to calculate the compression modulus under the strain of 5%. Mechanical testing results indicated that the compressive modulus of the composite hydrogel has a slightly smaller value than that of the porcine nucleus pulposus, but under the statistical analysis no significant difference between each other, and the results indicated that the composite hydrogel’s biomechanical behavior is similar to that of the porcine nucleus pulposus. After the composite hydrogel was implanted into the disc, compression to failure test were performed and the force - displacement curves were recorded for the Intact group, Denucleated group and Implanted group. The ultimate strength and ultimate displacement in the compression to failure test were found and the ultimate stiffness was calculated. The results showed that after the composite hydrogel was implanted into the decleated disc, the ultimate stiffness of disc can be restored, and there is no significant difference in respect to the Intact groups statistically. The results also indicated that the ultimate strength for the Implanted group is similar to that of the Intact group. After the composite hydrogel was implanted into the disc, the disc compressive stiffness under 15% strain was calculated for the compression to failure test. The results showed that the composite hydrogel can increase the disc strength after it was implanted into the disc. The compressive stiffness was also increased as the strain increases, and the non-linear load-displacement curve demonstrated that the disc possesses viscoelastic properties after the composite hydrogel was implanted into the disc. The creep test is performed and the displacement curve was recorded with time at a fixed pressure. The displacement-time curve for the creep test was fitted into a bi-phasic linear mathematical model to calculate the biphasic material properties ( HA、K0) of the disc. It was found that after the composite hydrogel was implanted, it can improve the aggregate modulus (HA) of the disc, and the permeability (K0) is similar to that of the Intact group. From the results found in this study, it is indicated that the new composite hydrogel may be a possible material to be used in future NP replacement device.
摘 要 I
誌 謝 VI
目 錄 II
表目錄 V
圖目錄 VI
第一章 緒論 1
1.1 前言 1
1.2 脊椎解剖學構造 2
1.2.1 椎骨 2
1.2.2 椎間盤結構與組成 3
1.3 椎間盤的生物力學 5
1.4 椎間盤退化性疾病(Disc degenerative disease, DDD) 6
1.5 椎間盤退化之治療方式 7
1.6 人工髓核置換術 8
1.7 髓核置換裝置 9
1.7.1 預成形髓核置換裝置 9
1.7.2 原位成形髓核置換裝置 10
1.8 水凝膠 11
1.8.1 水凝膠於組織工程應用 11
1.9 文獻回顧 12
1.9.1 雙相材料理論 12
1.9.2 自然髓核體外試驗 13
1.9.3 人工水凝膠體外試驗 15
1.9.4 人工水凝膠臨床追蹤 16
1.10 研究動機與目的 18
第二章 材料與方法 19
2.1 研究流程 19
2.2 實驗機台 21
2.3 實驗治具設計 22
2.3.1封閉治具 22
2.3.2固定骨水泥治具 23
2.4 水凝膠製作 23
2.5 豬腰椎試片 24
2.5.1 腰椎髓核組織 24
2.5.2 腰椎椎間盤 25
2.6 實驗流程 25
2.6.1 拘束壓縮測試 25
2.6.2 水凝膠植入椎間盤破壞壓縮測試 26
2.6.3 水凝膠植入椎間盤潛變測試 28
2.7 實驗數據分析 30
第三章 結果 31
3.1 拘束壓縮測試 31
3.1.1 豬腰椎髓核 31
3.1.2 人工水凝膠 32
3.1.3 豬腰椎髓核與人工水凝膠之比較 32
3.2 水凝膠植入椎間盤破壞壓縮測試 34
3.2.1 完整組 34
3.2.2 骨移除組 37
3.2.3 植入組 40
3.2.4 完整組、骨移除組、植入組之間的比較 43
3.3 水凝膠植入椎間盤潛變測試 46
3.3.1 完整組 46
3.3.2 骨移除組 47
3.3.3 植入組 48
3.3.4 完整組、骨移除組、植入組之比較 49
第四章 討論 51
4.1 拘束壓縮測試 51
4.2 椎間盤破壞壓縮測試 52
4.3 椎間盤潛變測試 53
4.4 研究限制 54
第五章 結論 57
文獻回顧 59
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