| 摘要: | 生物活性陶瓷如羥基磷灰石（HA）、β-磷酸三鈣(β-TCP)等皆是良好的骨質填充物，可提供蛋白質、成骨細胞極佳的生長環境。然而作為生醫材料，手術植入的修補等，需克服其擠壓定形困難及機械脆性。合成生物相容性的高分子如聚乳酸-羥基乙酸共聚物 (PLGA)、聚2-羥乙酯甲基丙烯酸 (PHEMA)等有良好的機械性質及可設計成所需求的物性，但其疏水性質不利於細胞組織的生長。因此複合材料如PHEMA /β-TCP，成為研究改良的方向。傳統的製程為將兩種奈米級的混合壓成複合材料錠或由機溶解液混織，再放置於超臨界二氧化碳(SCCO2)槽體中，使高分子的部分發泡產生孔洞。然而兩種材料之間的結合力不足、有機溶劑殘留及聚合完成的高分子不容易產生孔洞等等問題及缺點。有鑑於此，本計畫也針對生醫高分子合成核殻(core-shell)複合材料的製備方法做深入的研究。 為了避免溶劑的殘留，將實驗室已建立的反應設備，以SCCO2為溶媒，進行合成製備PHEMA/β-TCP。第一年的研究，是以甲基丙烯酸(HEMA)作為單體，以及利用三甲矽烷基醯胺化鉍 (Bis)為起始劑下反應聚合成生物相容性的高分子PHEMA。其中加入適量生物陶瓷β-TCP，進行攪拌使HEMA及β-TCP形成氫鍵鍵結，經由調整組成比例，以達成外殼部分為PHEMA，其疏水及親二氧化碳性質延展在SCCO2溶劑中，核心部分為親水性β-TCP，傾向遠離SCCO2，生成具有目標性的具有核殼結構的PHEMA/ β-TCP，且PHEMA於SCCO2中會發泡產生小孔洞。當應用於組織修補工程時，蛋白質組織可經由穿梭PHEMA孔洞到達β-TCP表面而便利生長，並以FTIR確認產物結構，SEM觀察表面形貌及其core-shell型態、SEM結合EDX進行偵測不同部位β-TCP的元素分析，掌握其分散性、TGA測量PHEMA熱裂解溫度(Td)，產率百分比計算等。第二年之研究，將尋求反應物/生物陶瓷用量比，以及實驗參數操作條件調整，反應壓力、反應時間及洩壓時間等，對複合物產品的平均分子量，比表面積及孔洞大小(BET)，吸水率，孔洞間穿透性，壓縮模數等性質的影響。將實驗數據進行分析，歸納出SCCO2聚合反應的參數關聯性與最適化關鍵因素，經由委託研究進行細胞毒性試驗實驗，測試生物組織相容性，評估實際的應用性並作為相關研究的參考。
Active ceramic such as hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) have hydrophilic surfaces which are excellent for osteogenic cell growth, but their difficulty in shaping and mechanical brittle properties are the limitations of their applications when implanted into the defection. On the other hand, synthetic polymers such as copolymer poly-lactide-co-glycotide (PLGA) and poly-2-hydroxyethyl methacrylate( PHEMA) can easily be formed into designed shapes with relatively high mechanical strength, but their hydrophobic surface is not favorable for cell seeding. Hybrids, such as PHEMA/ β-TCP, are formed for the ideal of scaffolds for tissue engineering, and the final composite scaffolds are always immersed in supercritical carbon dioxide (SCCO2) to become porous hybrid or the composites were fabricated in salt NaCl solution, such particulate leaching induced the massive formation of open pore structure for bone tissue engineering applications. Problems of the weak binding energy between two materials of the hybrid; organic solvent residual or difficulty of polymers foaming are to be overcome. In view of these, synthesis of biocompatible PHEMA/β-TCP core-shell composite by using the mild and advanced supercritical fluid technology is studied in this project. In the first year of study, with bismuth tris-silylamide (Bis) as initiator, monomer 2-hydroxyethyl methacrylate (HEMA), dispersed in SCCO2, as based material is polymerized as CO2-philic shell, PHEMA . Active ceramic β-TCP is linked by hydrogen bonding as the contributor of the hydrophilic core, to the final product, PHEMA/β-TCP, biocompatible core-shell composite, and the shell PHEMA/β-TCP will be foamed in SCCO2. Therefore, the properties of PHEMA and β-TCP can be tuned individually. The structure of the result product can be confirmed by Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), SEM images will show the size and morphology of products and will observe the composite core-shell appearance, Elements of β-TCP are detected by Energy-dispersive X-ray spectroscopy (EDX), the degrading temperature of polymer is studied by Thermogravimetric Analysis (TGA) and the yield percentage will be calculated. In the second year, we will also investigate the effects of reaction factors. The influence of the impregnation of monomer, and active ceramic ratio, reaction time, and conducting pressure and venting time are investigated. Furthermore, pore size and surface area, measurements of average molecular weight, water uptake, pore interconnectivity, compression modulus and cell culture cytotoxicity test will be examined in this year. The results for optimal operation conditions are expected that are valuable to future industrial applications and bone tissue engineering applications. |
