摘要
本研究利用幾丁聚醣作為血管支架的主要材料，以化學共價交聯的方式製備出具形狀記憶的螺旋形支架，並包覆抗血管內膜增生藥物sirolimus於支架中，製備一可完全生物分解的藥物制放型血管支架。本研究主要分為三部分。第一部份的目的為製備一具有良好機械性質的螺旋形血管支架。利用天然交聯劑genipin進行交聯處理，將幾丁聚醣混成膜定形成螺旋形。實驗結果證實，以1% genipin、兩倍離子強度的磷酸鹽溶液於37℃下交聯支架三小時，可將支架定形成一完美的螺旋形，並具有較佳的機械性質。第二部份為支架的體內生物相容性評估，將血管支架植入兔子的腹主動脈中，經過一天後取樣，並沒有急性血栓產生，且支架結構完整；植入一個禮拜後，血管會有較強的發炎反應發生；而經過三個月之後，發炎的情況減緩，不過仍無法避免內膜增生的情形。第三部分為製備藥物制放型之血管支架，以期改善內膜增生的問題。探討不同包藥量及塗佈Duraflo肝素，對血管支架之藥物釋放動力學的影響。由實驗結果可知，未塗佈Duraflo肝素的血管支架會有burst release的情況；反之，支架上塗佈Duraflo肝素，可延緩藥物之釋放，其釋放模式接近零次釋放。為了證實由支架所釋放出的sirolimus，仍具有其藥物活性，因此本研究將所製備的支架與平滑肌細胞共培養，並進行MTT assay的定量分析、螢光顯微鏡的定性觀察(Life/Dead Viability)與流式細胞儀的cell cycle分析。結果證實，支架所釋放之sirolimus仍保有其藥物活性，可讓平滑肌細胞停滯於cell cycle週期中的G1 phase，達到抑制平滑肌細胞增生的效果。綜合以上的結果，經genipin交聯處理的藥物制放型血管支架，確實具有良好的機械性質與體內的生物相容性，其釋放之sirolimus可有效地抑制平滑肌細胞的增生，預期可發展成為新一代之生物可分解式之藥物制放型血管支架。

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