多酚類分子輔助高分子之抗污表面改質處理

Abstract

表面改質在醫療產業中如骨科、牙科、眼科及生物感測中十分廣泛的被應用。由於生醫材料的表面和體內環境有第一時間的接觸，其表面的性質將會決定此生醫材料成效，因此許多人利用表面改質技術來改變或改善生醫材料的性質。為了要避免蛋白質吸附及進一步的細胞貼附而導致醫療器材的效能降低或者疾病之產生，表面修飾抗污塗層被用來解決這類問題。然而現今許多表面改質的方式對於不同的基材有極大的專一性，因此我們發展出一步驟共聚塗佈的方式，將抗污高分子聚乙烯醇及兩性高分子磺基甜菜鹼藉由鄰苯三酚自我聚合方式固定在各類表面上。當聚乙烯醇末端含有醛基或兩性磺基甜菜鹼共聚高分子含有胺基單體時，這些抗污高分子能和鄰苯三酚進行反應進而固定於表面上，對纖維母細胞及蛋白質產生極佳的抗污作用。 我們在浸泡塗佈法中控制不同的塗佈時間，以期能得到表面性質和細胞貼附行為間的關係。此抗污塗層的效果和表面的親水性呈現正相關，當此抗污塗層厚度達到50奈米或表面抗污高分子嫁接比例超過50%時，此抗污塗層將會有很好的抑制細胞貼附效果。同時，我們也發現抗污高分子在溶液中比鄰苯三酚更先消耗完畢，因此在浸泡塗佈法中塗佈時間必須精準地控制以達到最佳的抗汙效果。此外，此抗污塗層在經過高壓釜滅菌處理後能保持很好的抗細胞貼附效果。另外，由於此塗佈的薄膜十分的透明，我們期望此技術能應用在需要高度透光性的塗層的醫療器材上像是人工水晶體。 藉由一步驟多酚類電沉積法，此抗污塗佈處理時間能大幅縮短至800秒。我們將導電玻璃上塗佈兩性高分子抗污塗層後能使表面對於生物分子有良好的抗貼附效果，同時也能維持基材既有的優良導電性。當我們再將生物素嫁接於兩性高分子上時並進一步驟鄰苯三酚電沉積，此系統能對特定抗生物素分子具有捕獲效果，但卻可以對其他非特定性蛋白干擾有很大的抗汙效果，因此我們希望此技術能在將來被應用生物感測器上。

Surface modification has become a routine procedure in designing and developing bio-friendly implants for orthopedic, dental and ophthalmology applications as well as other bio-sensing applications. The surface of biomaterial affects its performance in a host environment. Many techniques have been utilized to modify the surfaces of biomaterials to obtain innovative or improved properties. In order to prevent protein adsorption and further cell adhesion, which decreased sensitivity of medical device or caused disease on patients, surface modification for anti-fouling purpose is an important strategy to address this issue. However, many methods for conjugation of anti-fouling materials on surfaces are substrate-dependent. We developed a simple one-step coating method for surface immobilization of antifouling polymers sulfobetaine methacrylate (SBMA) or poly (ethylene glycol) (PEG) via deposition of self-polymerized pyrogallol (PG). The anti-fouling polymers were successfully anchored on various substrates when the SBMA conjugation of monomers containing amine groups or PEG tailing with aldehyde groups. The modified surfaces exhibited excellent resistance to fibroblast cells and proteins. Controlling the coating for an array of incubation time in dip coating method, we investigated through the surface properties corresponding to cells adhesion behaviors. The antifouling effect on the surfaces is positive correlation with the surface wettability. When the antifouling film reached 50 nm and the grafting ratio of antifouling polymers reached 50%, the surfaces can inhibit cell growth effectively. Meanwhile, we found antifouling polymers are consumed faster than PG in the coating solution, so the required coating time for antifouling surface fabricated by dip coating should be controlled precisely. Besides, this coating treatment is robust enough for the duration of harsh environment such as autoclave. We also believe the high transparency of this coating can allow this strategy applied on the development of new generation medical devices such as intraocular lens. The required coating time can be significantly reduced to only 800 seconds by the one-step polyphenol electrodeposition method. The ITO surfaces are endowed with antifouling feature to repel biomolecules attachment but maintain the intrinsic good conductivity of the substrates. With the grafting of biotins on the zwitterionic copolymers, followed by the co-electrodeposition with PG, the surfaces can capture specific target avidin but resist the interference non-specific protein adsorption in complex media. We hope this treatment can also be applied into the area of biosensor.