研究生: |
林建宏 Chien-hong Lin |
---|---|
論文名稱: |
聚二甲基矽氧烷混成水膠薄膜之改質及其眼科性質之探討 Modification of polydimethylsiloxane hybrid hydrogel membranes for ophthalmic properties |
指導教授: |
楊銘乾
Ming-chien Yang |
口試委員: |
鍾竺均
Ying-Chien Chung 張豐志 Feng-chih Chang 許應舉 Ying-gev, Hsu 王大銘 Da-Ming Wang |
學位類別: |
博士 Doctor |
系所名稱: |
工程學院 - 材料科學與工程系 Department of Materials Science and Engineering |
論文出版年: | 2010 |
畢業學年度: | 98 |
語文別: | 中文 |
論文頁數: | 161 |
中文關鍵詞: | PDMS預聚物 、幾丁聚醣 、透明質酸 、F127 、PEGMA 、親水性 、蛋白質吸附 、透氧性 、無毒性 、矽水膠 、眼科材料 |
外文關鍵詞: | PDMS macromer, non-cytotoxic |
相關次數: | 點閱:619 下載:15 |
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本研究利用PDMS-diol為軟鏈段,IPDI為硬鏈段與HEMA為鏈延長劑來合成聚矽氧烷凝膠 (PDMS-HEMA) 作為基材。對於此PDMS-HEMA基材,本論文以三種方式加以改質,以作為眼科材料。第一種方式是利用層接式自我組裝方法形成多層聚集來進行PDMS-HEMA的表面改質。第二種方式,則利用Pluronic F127以混摻的方式與PDMS-HEMA形成混摻水膠。第三種方式,係利用PEGMA以共聚合的方式與PDMS-HEMA形成共聚合水膠。
在本論文的第一部分,將PDMS-HEMA,利用氧電漿活化表面,進行丙烯酸接枝,於膜表面產生-COO-基團,然後利用幾丁聚醣(chitosan,CS)與透明質酸 (hyaluronic acid,HA)以層接式自我組裝形成多層聚集結構。由AFM觀察可知聚電解質多層結構之PDMS-HEMA薄膜粗糙度會些微上升。由染料確認可得知幾丁聚醣與透明質酸接枝量也隨固化層增加有線性增加趨勢。接觸角會因透明質酸接枝密度的增加而降低,如此更使親水性提高。由於幾丁聚醣與透明質酸量增加更降低PDMS-HEMA薄膜之蛋白質吸附。此外,在含水率、透氧率與透光率方面,改質前後的PDMS-HEMA無明顯變化。
第二部分,利用Pluronic F127以混摻的方式與PDMS-HEMA形成混摻水膠(PDMS-F127)。由實驗結果可知,其含水率隨著Pluronic F127增加而上升,而接觸角也因Pluronic F127的加入而降低,因而提高水膠的親水性,然而透氧率(oxygen permeability,Dk )則相對地降低,但降低的量並不大,而透光率也有些微地降低。在機械強力(mechanical strength)及楊氏係數(Young’s modulus)方面會隨著Pluronic F127的增加而有下降的趨勢。而在蛋白質吸附試驗中,我們利用BCA蛋白質測定方法來探討,結果顯示Pluronic F127上由於立體結構的影響而能抑制lysozyme的吸附。在細胞毒性方面,以ISO10993-5的判定上屬於0-1級,所以其細胞毒性甚低。
第三部分,PEGMA以共聚合的方式與PDMS-HEMA形成共聚合水膠(PDMS-PEGMA),由結果得知,在PDMS-PEGMA矽水膠中,PEGMA的含量愈多會使得接觸角角度愈低、含水率愈高、葡萄糖滲透量也會愈高。楊氏係數會隨著PEGMA的增加而減少。然而透氧率則相對地降低,但降低的量並不大,而透光率也有些微地降低。在蛋白質吸附試驗中,PEGMA能有效的抑制lysozome的吸附。在L929纖維母細胞毒性測試,可得知PDMS-PEGMA並無毒性。
綜合以上結果,PDMS-HEMA經由表面、混摻、共聚合的方式改質後的矽水膠,具有優異的透光性、透氧性、親水性、抗蛋白且無細胞毒性,對於作為眼科材料有相當大的潛力。
A novel polydimethylsiloxane (PDMS) based hydrogel was synthesized for ophthalmical applications. This novel hydrogel was consisting of soft segment of poly(dimethylsiloxane) dialkanol and hard segment of isophorone diisocyanate (IPDI). In addition, 2-hydroxyethyl methacrylate (HEMA) was added as the chain-extender to form UV curable silicone marcomer. This PDMS-HEMA macromer was subject to three kinds of modifications.
In the first part, the surface of PDMS-HEMA gel membrane was treated with oxygen plasma, followed by graft-polymerization of acrylic acid (AA), Subsequently, chitosan (CS) (as positively charged agent) and hyaluronic acid (HA) (as negatively charged agent) were alternatively deposited onto the carboxylic PDMS-HEMA hydrogels in a layer-by-layer assembly manner, thereby constructing polyelectrolyte complex (PEC) multilayers. The results from AFM show that the surface roughness changed little with the deposition of PEC layers. The hydrophilicity was improved with the increase of the number of PEC layers. The adsorption amount of protein (lysozyme) decreased with the number of PEC layers. In addition, the oxygen permeability (Dk) and the optical transmittance were not significantly affected by the surface modification. Furthermore, these hydrogel membranes were non-cytotoxic through in vitro L929 fibroblasts assay.
In the second part, the PDMS-HEMA marcomer was blended with Pluronic F127 triblock copolymer. The results show that the increase in Pluronic F127 content led to the decrease of water contact angle and the increase of water content the blend hydrogels. Young’s modulus also decreased with the increase of Pluronic F127 content, while surface roughness was not significantly affected. When the Pluronic F127 content reached 4%, the apparent protein adsorption amount decreased to about 60% of that of PDMS-HEMA control. Thus the PDMS-F127 hydrogel membrane had an excellent ability to resist protein adsorption. Additionally, the oxygen permeability (Dk) would decrease by 24%, comparing with PDMS-HEMA control. Furthermore, these hydrogel were non-cytotoxic through in vitro L929 fibroblasts proliferation assay. Overall results demonstrated that the PDMS-F127 blending hydrogel provided silicone hydrogel materials not only having relatively high oxygen permeability and a relatively low modulus, but also enhancing hydrophilicity and anti-protein adsorption.
In the last part, PDMS-HEMA was reacted with PEGMA under UV-photo initiation, resulting a copolymer (PDMS-PEGMA). The results showed that higher PEGMA content led to lower water contact angle, higher water content and higher glucose permeability for these silicone hydrogels. Young’s modulus also decreased with the increase of PEGMA content. At a PEGMA content of 20%, the adsorption of lysozyme decreased to 23% of that of the PDMS-HEMA control. This indicated that the PDMS-PEGMA hydrogels exhibited an ability to resist protein adsorption. In addition, the oxygen permeability (Dk) would remain 74% of that of the PDMS-HEMA control. Furthermore, these hydrogels were non-cytotoxic through in vitro L929 fibroblasts assay. Overall results demonstrated that the PDMS-PEGMA hydrogels exhibited not only relatively high oxygen permeability and a relatively optical transparency, but also hydrophilicity and anti-protein adsorption, therefore would be applicable as ophthalmic material.
Overall results demonstrated that such an easy processing and rapid method should have good potential for modification of PDMS-HEMA in the application of ophthalmic material with biocompatibility, cytocompatibility, and hydrophilicity.
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