- 學位論文
以化學改質海藻酸鈉模擬玻尿酸及其生醫應用之潛力
Chemical Modification of Alginate to Mimic Hyaluronic Acid and its Biomedical Applications Potential
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摘要
玻尿酸（HA）是一個影響眾多生理功能的天然多醣，被普遍廣泛應用於臨床研究中。目前，生產玻尿酸的主要方式包括於動物組織精煉提取、微生物發酵以及酵素生產。然而，部分方式由於製造成本過高、產量較低，框架了在大量生產的可實行性。因此，尋找玻尿酸的替代生產路徑需要被高度重視。 因此設計一種化學改質方法，利用EDC反應將海藻酸鈉轉化為類似玻尿酸的材料。在合成的類玻尿酸材料（ALG_1、ALG_2和ALG_4）中，ALG_4在傅立葉轉換紅外線、氫及碳原子核磁共振光譜和元素分析中表現出與玻尿酸最為相似。此外，ALG_4對於高表達CD44和CD168的MDA-MB-231顯示出極高的生物效應，而對於低表達CD44和CD168的MCF-7細胞的影響較少，此現象使ALG_4具有癌症治療之應用的價值。 術後沾黏是術後常見的後遺症，受傷的組織持續滲血使纖維蛋白充滿整個腹腔，讓纖維細胞得以貼附。本研究透過ALG_4與海藻酸鈉水溶液充分混參並與氯化鈣交聯，成功形成了一種可被生物吸收的抗沾黏膜。此抗沾黏膜不僅在物理上有效地分離組織和器官，還能有效地減少纖維蛋白的吸附以及纖維母細胞的貼附，從而有效減輕術後沾黏的發生。 不僅提供了創新的海藻酸鈉化學改質成類玻尿酸材料的方法，更展現了ALG_4於醫學工程領域多元且廣泛的應用潛力。ALG_4作為一種類玻尿酸材料，有望其於抗沾黏、癌症治療以及其他醫學工程的應用中，成為一種能替代玻尿酸的新興的方法。
並列摘要
Hyaluronic acid (HA) is a naturally derived polysaccharide that plays roles in various physiological functions and is widely used in medical applications. HA production methods primarily include extraction from animal tissues, microbial fermentation, and enzymatic production. However, some methods are often associated with high costs and low yields, limiting their industrial feasibility. Therefore, exploring alternative production routes for HA is extremely important. This study proposes a chemical modification method using EDC reaction to make alginate into a hyaluronic acid-like material. Among the HA-like materials (ALG_1, ALG_2, and ALG_4), ALG_4 exhibited the closest similarity to HA as confirmed by FT-IR, NMR, and elemental analysis. Furthermore, ALG_4 showed significant biological effects on MDA-MB-231 which shows extremely high expresses to CD44 and CD168, while having less impact on MCF-7 cells with low expression of these markers. This indicates its potential application in cancer treatment. Postoperative adhesions are a common complication following surgery, where injured tissues continue to bleed, causing fibrin to fill the abdominal cavity and allowing fibroblasts to adhere. In this study, ALG_4 blends with alginate solution and crosslinked with calcium chloride successfully formed a bioabsorbable anti-adhesion membrane. This membrane not only physically separated tissues and organs but also significantly reduced the adhesion of fibrinogen and fibroblasts, effectively reducing the occurrence of postoperative adhesions. In conclusion, this study demonstrates an innovative chemical modification method for alginate and reveals its extensive potential applications in the biomedical field. ALG_4, as a hyaluronic acid-like material, holds promise for use in anti-adhesion, cancer treatment, and other medical applications, providing a viable solution as an alternative to current hyaluronic acid products.
參考文獻
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