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  • 學位論文

發展應用於軟骨組織工程之硫酸軟骨素為基底的可注射性水膠

The development of injectable chondroitin sulfate based hydrogels for cartilage tissue engineering

指導教授 : 蔡偉博

摘要


關節軟骨因爲缺乏血管的緣故,所以它的自我修復能力非常差。正因如此,所以對於軟骨增生的治療仍然困難重重。雖然目前的治療方法,例如膝關節置換和自體細胞移植等,雖然可以治療軟骨的缺損問題,但以上方都各有優缺點。 基於這個原因,本題目會以組織工程的方向入手,以祈望可以解決上述的問題。此研究中,我們會開發以軟骨素為主體的可射性水膠的基材,再分別混合明膠、膠原蛋白以及去細胞化軟骨,這些在多篇文獻上均以被證明對軟骨細胞的生長以及分化有正面影響的材料,以研究它們對於軟骨細胞的生長以及分化的差異。 此外,我們會使用過氧化物酶(HRP)和過氧化氫(H2O2)這個系統使軟骨素交聯形成水膠,再分析它們的各項材料特性。 研究結果顯示,通過改變酶的濃度,我們可以改變水膠的成膠時間,大大的提升了以後在臨床應用上的效率。此外,通過加入了膠原蛋白、明膠或去細胞化軟骨後,水膠的機械強度大大提升,使得它更接近細胞生長環境。 而細胞實驗顯示,水膠對於細胞近乎沒有毒性。不僅如此,跟只有軟骨素的組別比較,混合了其他材料的組別更能促進細胞的生長與分化。

並列摘要


Due to the lack of blood vessels, articular cartilage lacks of the ability of self-healing. As a result, it is a great challenge to cue the cartilage defect. There are several approaches available now to deal with this problem. For example, the knee joint replacement and autologous cell implantation. But these methods have their own weakness. So, we want to solve this problem by the means of tissue engineering. Our research would develop a scaffold based on injectable chondroitin sulfate based hydrogel, with the mixing of collagen, gelatin or decellularized cartilage, these materials have been proven their abilities in enhancing the cell growth and differentiation, studying their differences in promoting cell growth and differentiation. Besides that, we used horseradish from peroxidase (HRP) and hydrogen peroxide (H2O2) to crosslink modified chondroitin sulfate, and studied their properties. The results showed that changing the enzyme concentration can change the gelation time, which making the applications more convenient. On the other hand, by the adding of collagen, gelatin or decellularized cartilage, the mechanical strength of the hydrogel greatly increased. The cell experiment showed that the hydrogel had nearly no cytotoxicity. Moreover, the groups with collagen, gelatin or decellularized cartilage had a much better results in promoting cell growth and differentiation than the chondroitin sulfate one.

參考文獻


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2. Hunziker, E.B., M. Michel, and D. Studer, Ultrastructure of adult human articular cartilage matrix after cryotechnical processing. Microscopy Research and Technique, 1997. 37(4): p. 271-284.
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