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  • 學位論文

生醫材料表面改質應用於降低宿主反應及藥物釋放

Application of Surface Modification on Biomedical Device in Drug Delivery and Resistance to Host Response

指導教授 : 蔡偉博

摘要


在生醫材料植入體內中,最常見的問題就是身體無法成功的自我修復。此狀況在長時間下會導致異物反應,並且驅使夾囊包覆的形成。在這個研究中,主要是以高分子塗佈的方式改質生醫材料表面,並利用其表面包覆抗發炎藥物來降低體外實驗巨蝕細胞的啟動及貼覆,跟體內實驗夾囊包覆的形成。在研究的第一個階段,我們成功利用一種光交聯親水高分子p(PEGMA-co-AA)-g-Az改質於聚甲基丙烯酸甲酯的表面,並且在細胞實驗中觀察到此改質方法能夠降低RAW264.7巨噬细胞的貼附及活化。另外,當探討改變塗布時的pH值及PEGMA與acrylic acid的聚合比例對巨噬细胞的影響時,可看出在pH 6.5下,PEGMA: Acrylic Acid等於9:1條件下可得到較低的細胞貼附及夾囊包覆。在第二階段的研究中,我們使用前述的條件來包覆含有30%抗發炎藥物酮基布洛芬(Ketoprofen)的聚乳酸聚甘醇酸(PLGA)微粒子,同樣進行上述細胞貼附與夾囊包覆之實驗。在實驗中我們發現此藥物成功的被包埋且能夠緩慢釋放,雖然研究中顯示巨噬细胞的貼附並沒有因為包覆藥物而有明顯差異,但在體內植入實驗卻有效的降低夾囊包覆的形成。

並列摘要


Failure in turning on normal healing process has always been one of the major obstacles and complications in long-term artificial implants surgery. This can lead to possible foreign body reaction (FBR), where the implants may be encapsulated by fibrous collagen layer. In order to reduce host response, a facile polymer coating method was utilized in this study in reducing host response and foreign body reaction. In part 1 of this study, PMMA samples modified with p(PEGMA-co-AA)-g-Az copolymer successfully lowers RAW 264.7 cell adhesion and activation, with coating pH value of 6.5 and ratio of 9:1 PEGMA to acrylic acid copolymerization condition to exhibit lower macrophage adhesion. In vivo study also showed 13-15% reduction in encapsulation thickness with p(PEGMA-co-AA)-g-Az modified samples in compared to PMMA control. In part 2 of this study, the hydrogel successfully entrapped 30% (v/v) ketoprofen-PLGA micro-particles with low and sustained local release of anti-inflammatory drug. Though no difference in cell adhesion was observed with presence of ketoprofen, further in vivo analysis showed statistically lower encapsulated thickness with presence of ketoprofen in compared to p(PEGMA-co-AA)-g-Az without ketoprofen and PMMA control.

參考文獻


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