研究穩定抗生物分子沾黏材料之分子結構設計、改質程序建構及生物醫學應用

自二戰時期到現在，生物惰性材料已發展超過80個年頭，科學家們已了解到利用氫鍵受體或是雙離子結構，可產生厚實的水合層來屏蔽生物分子。然而，進行生物惰性的改質時，由於表面自由能與粗糙度的影響，會讓改質劑難以良好地附著在材料表面上，並在乾燥過程中產生皺縮甚至龜裂的現象。此外，目前的化學接枝方式不但程序繁瑣又耗時，使用藥劑又對環境不友善。而更令人煩惱的是，目前絕大多數的改質劑都是使用具有酯類或是醯胺類官能基的壓克力材料，對於長時間在生物環境中使用會有水解的疑慮，進而導致使用壽命減少的風險產生。　　因此，本論文將分別著重在－改質物的附著性提升、快速化學接枝、抗水解之生物惰性結構設計等三部份進行探討。以期望未來的生醫材料之設計與生產，能夠朝向穩定而快速的改質以及耐用來發展。　　本論文第一部份使用常壓空氣電漿進行5分鐘的表面活化，使表面氧元素增加24倍，並大幅降低改質物PS-co-PEGMA的聚集現象。而超音波微粒噴塗技術不但可精確控制改質密度達0.01 mg/cm2，且當達到0.3 mg/cm2時，表面即被改質物完整覆蓋。以此技術進行生化檢測盤改質，可提升8倍的檢測靈敏度，使試劑即便稀釋128倍，仍具有高度辨識性。　　本論文第二部份使用親水性雙離子環氧樹脂Poly(GMA-co-SBMA)搭配UV光固化技術，可使每平方公尺的PET不織布纖維薄膜僅需11.5 g的高分子，並照光不到30分鐘，即可降低近8成的血液貼附及9成的細胞貼附。未來對於PU及PEEK的改質，或是應用在微流道及微型晶片實驗室之領域，這種一步驟快速化學接枝的清潔製程，具有相當大的應用潛力。　　本論文第三部份使用非壓克力型雙離子高分子zP(S-co-4VP)，對材料進行快速的自組裝塗佈改質。不但可降低98%的細菌與血液貼附量，且經過高溫濕式滅菌後的細菌貼附量僅上升74%，而壓克力型雙離子高分子P(S-co-SBMA)卻增加192%。這對於未來在發酵產業、反覆滅菌、長時間使用等需求來說，具有相當大的應用潛力。

關鍵字

穩定；抗沾黏；生醫材料；生物惰性；表面自由能；環氧基；壓克力材料；水解；電漿；超音波噴塗；紫外光固化

並列摘要

Since World War II to the present, bio-inert materials have been developed for more than 80 years. Scientists have learned that the use of hydrogen bond acceptors or zwitterionic structures can produce a thick hydrated layer to shield biomolecules. However, when performing bio-inert modification, due to the influence of surface free energy and roughness, it is difficult for the modifier to adhere to the surface of the material, and shrinkage or even cracking occurs during the drying process. In addition, the current chemical grafting methods are not only cumbersome and time-consuming, but the use of chemicals is also unfriendly to the environment. What’s more annoying is that most of the modifiers currently use acrylic materials with functional groups of esters or amides, which may cause hydrolysis when used in a biological environment for a long time. The risk of reduced service life arises. 　　 Therefore, this thesis will focus on three parts: the improvement of the adhesion of the modified substance, the rapid chemical grafting, and the bio-inert structure design for hydrolysis tolerance. It is hoped that the design and production of biomaterials in the future can develop towards stable and rapid modification and durability. 　　 In the first part of this research, atmospheric air plasma pretreatment was used to activate the surface for 5 minutes, which increased the surface oxygen element by 24 times and greatly reduced the aggregation of the modified PS-co-PEGMA. Ultrasonic spraying deposition technology can not only accurately control the coating density to 0.01 mg/cm2, but when it reaches 0.3 mg/cm2, the surface is completely covered by the modifier. Using this technology to upgrade the biochemical detection plate can increase the detection sensitivity by 8 times, making the reagents highly recognizable even if they are diluted 128 times. 　　In the second part of this researcg, the use of hydrophilic zwitterionic epoxy resin Poly(GMA-co-SBMA) with UV-curing can make the PET non-woven fibric membrane only need 11.5 g of polymer per square meter and the UV-curing is within less than 30 minutes, it can reduce blood attachment by nearly 80% and cell attachment by 90%. In the future, for the PU and PEEK, or the application in the field of micro-fluidic chip, this one-step rapid chemical grafting cleaning process has considerable application potential. 　　 The third part of this research uses non-acrylic amphiphilic zwitterionic polymer zP(S-co-4VP) to perform rapid self-assembly coating modification on the material. Not only can reduce the attachment amount of bacteria and blood by 98%, but the amount of bacteria attached after sterilization only increases by 74%, while the acrylic zwitterionic polymer P(S-co-SBMA) increases by 192%. This has considerable application potential for future needs in the fermentation industry, repeated sterilization, and long-term use.

並列關鍵字

Stable ； Antifouling ； Biomaterials ； Bioinert ； Surface free energy ； Epoxy ； Acrylic material ； Hydrolysis ； Plasma ； Ultrasonic spray ； UV-curing

參考文獻

[1] Oeppen, J., Vaupel, J. W. (2002). Broken Limits to Life Expectancy. Science, 296(5570), 1029-1031. doi: 10.1126/science.1069675

Google Scholar

[2] 陳柏如（2018）。研究以互穿式高分子網絡包覆法製備雙離子性聚丙烯纖維薄膜與探討其生物相容性質。未出版之碩士論文，中原大學化學工程研究所，桃園縣。

Google Scholar

[3] Vert, M., Doi, Y., Hellwich, K.-H., Hess, M. J., Hodge, P., Kubisa, P., Rinaudo, M., Schué, F. (2012). Terminology for biorelated polymers and applications (IUPAC Recommendations 2012). Pure and Applied Chemistry, 84, 377 - 410. doi: 10.1351/PAC-REC-10-12-04

Google Scholar

[4] Ghasemi-Mobarakeh, L., Kolahreez, D., Ramakrishna, S., Williams, D. (2019). Key terminology in biomaterials and biocompatibility. Current Opinion in Biomedical Engineering, 10, 45-50. doi: 10.1016/j.cobme.2019.02.004

Google Scholar

[5] Biomaterials. from https://www.nibib.nih.gov/science-education/science-topics/biomaterials

Google Scholar

國際替代計量

研究穩定抗生物分子沾黏材料之分子結構設計、改質程序建構及生物醫學應用

全文下載

主題瀏覽