Abstract
本研究以低溫電漿誘導接枝聚合反應將親水性單體接枝於矽膠表面上，以表面分析儀器鑑定改質薄膜的性質，探討各單體聚合接枝特性如：官能基變化、反應條件對表面接枝的影響、表面親疏水性、表面形態及生物適應性等，再選擇適當的材料製作雙面異功能性高分子薄膜，以期製備一具有臨床應用價值的人工眼角膜。研究首先採用高透氣性、透光性且高強度的矽膠薄膜作為基材，以新型的電漿誘導接枝聚合反應，將具特殊功能的丙烯酸，甲基丙烯酸羥乙酯，磷脂質單體進行接枝聚合；另將聚乙二醇或膠原蛋白經偶合劑固定於矽膠表面，達到改質的目的；接以全反射霍式紅外線光譜(ATR-FTI R)、表面化學元素分析(ESCA)、二次離子表面質譜儀(SIMS)、掃瞄式電子顯微鏡 (SEM)及接觸角分析儀(contact angle)分析改質薄膜表面的官能基及親疏水性；以細胞培養、蛋白質吸附及血小板附著活體外試驗分析改質材料表面的生物適應性，進而以兔子眼睛做全層角膜移植手術(環刀傷口 7.0mm)瞭解改質材料植入動物體內的各項免疫反應。綜各式薄膜的試驗結果得知，不同單體或接枝量均影響上皮細胞的附著生長。 另一方面詳細研究不同改質高分子薄膜進行血清蛋白(BSA)吸附及血小板附著分析結果顯示，蛋白質的吸附情形與細胞附著現象有平行的效果；除了 PEO-3350 和 pMPC-grafted SR 可有效抑制血小板堆積外，其餘測試薄膜表面血小板均發生堆積現象。基於以上之研究結果，利用新設計反應器製被備雙面異功能性高分子薄膜，於薄膜正面接枝膠原蛋白而背面接枝磷脂質作為植入性人工眼角膜。並於兔子活體實驗中，得到角膜上皮細胞於手術一星期後可完全覆植於薄膜上，且眼睛前房深度可維持正常。兩星期內無炎性反應及不正常分泌物及透明度可達 95% 以上。同時手術傷口可於兩個月後癒合,得一新生角膜組織，使眼球結構維持完整，提供良好二次移植手術的環境，使手術後捐贈角膜有更高的存活率，並提高術後的成功率。此外，由病理切片結果分析，不良的植入薄膜於傷口癒合過程中無法建立完整的組織。相反的，生物親和性佳的薄膜，在傷口重建過程，不僅炎性反應發生率低，新生的組織也接近原角膜，使手術後兔子有舒適的癒合環境。故此雙面異功能性高分子薄膜對小傷口角膜缺損可適時重建眼球之完整性而達到治療的效果，於臨床上的應用極具潛力，此對台灣眼庫不具有效運作能力之環境，尤具實質的意義。In this study, we perform surface modification of siliconerubber (SR) with various vinyl monomers via plasma-inducedgraft coplymerization (PIP). The surface properties of modifiedSR such as functional groups, grafted amount, hydrophilic/hydrophobic, surface morphology and biocompatibility arediscussed before and after modification. Some appropriateledaquate monomers are selected to prepare a heterobifunctionalmembrane. Furthermore, this membrane is highly promising forclinical ophthalmology. The high gas permeability, hightransparent and high strength material-SR membrane was used asa substrate. Surface modification of SR was performed withplasma induced graft copolymerization with vinyl monomers suchas acrylic acid (AA), 2-hydroxyethyl methacrylate (HEMA), and2-methacryloyloxy ethylphosphorylcholine (MPC).In addition,thesurface properties were characterized with an attenuated totalreflection/fourier transform infrared (ATR-FTIR), elementspectra for chemical analysis (ESCA), secondary ion massspectra (SIMS), scanning electronic microscope (SEM) andcontact angle meter. In vivo results of the heterobifunctionalmembrane surface of a modified silicone membrane indicated thatinert splinting would aid in the successful corneal woundhealing in a huge (7.0 mm) full-thickness defect, which ishighly promising for clinical applications. Posterior synechiaefrequently occurs after operation. Such a this problem can beresolved by pMPC grafting the membrane's lowerside surface.Also, the characteristics of in vitro epithelial affinity werenot verified by epithelial growth over the membrane throughthis in vivo study. Moreover, the host cornea could not bindwith the implant membrane. Therefore, the implanted membranefinally dislodged several months after post-operative surgery.Above difficulties can hopefully be resolved by using thisnovel material. Furthermore, a permanent artificial cornea canhopefully made for future ophthalmological applications.