- 學位論文
新型抗菌奈米矽片生醫複材之根管封填應用
The Novel Composite Biomaterials with Nanoscale Silicate Platelets as Antibacterial Agents for Root Canal Obturation
摘要
根管治療的目的為將受感染的牙髓移除，以填充材料密封達到防止微生物再度感染根管系統，目前根管封填材料仍無法達到有效根管治療的目的。根據過去研究團隊研究之結果顯示，合成之聚氨酯根管封填材料系統在臨床操作上有極佳的機械性質及熱性質等，然而此類材料不僅無抗菌性且有水解之疑慮導致細胞毒性較高。 本研究主要建立新型抗菌根管封填材料系統，原材料部份以CO2/ethylene carbonate (EC)衍生單體，即聚碳酸酯(Polycarbonate Polyol, PCPO)以取代傳統之 polyester-polyol or PTMEG作為主要新軟鏈段，以增加最終材料之生物相容性，再以鏈延長劑(1,4-butanediol, 1,4-BD)及壓克力單體(2-hydroxyethyl methacrylate, HEMA)各別合成熱塑性聚氨酯基材及光可硬化之氨酯壓克力樹脂。而抗菌無機填料則以本實驗室開發多年之”奈米矽片”；利用設計之PCPO其高陰電性官能基以分散奈米材料製備出具有生物相容性佳、機械性質良好及抗菌性的三功能性根管封填錐體與根管封填劑。 結果顯示: 透過DSC測試得知，六亞甲基二異氰酸酯（1,6-diisocyanatohexane, HDI）所合成之熱塑性聚氨酯相較於其他二異氰酸酯合成之聚氨酯具有最高熔點，以莫耳比HDI/polyol/1,4-butanediol=11/10/1合成之熱塑性聚氨酯為根管封填錐體之樹脂，同樣地透過DSC測試得知將NSP導入樹脂中可提升其熔點，並發現以PCPO為軟鏈段之熱塑性聚氨酯其熔點較低，但其融化熱與馬來膠錐體相似較不危害牙齒組織。透過機械測試，奈米矽片(NSP)之聚碳酸酯型聚氨酯複合材料具有良好之機械性質，其中以添加百分之五重量百分濃度奈米矽片材料(NSP)之聚碳酸酯型聚氨酯複合材料具有最佳之機械性質，並且其熱性質與馬來膠錐體相似，因此此複合材料於根管治療臨床應用上之可行性。根管封填劑的部分，透過ISO 6876:2001法規之流動性分析，氨酯壓克力樹脂以七比三之重量比例和三丙烯乙二醇雙丙烯酸酯混合之樹脂流動性最適當。透過機械測試，光啟始劑以百分之三重量百分濃度可使氨酯壓克力樹脂得到最佳機械性質。透過固化深度測試發現NSP抗菌劑之添加比例增加，固化深度則下降。由Alamarblue assay測試得知具有NSP抗菌劑之氨酯壓克力樹脂其生物相容性良好，而LDH assay測試可得知以PCPO合成之氨酯壓克力樹脂其細胞毒性低於PTMEG合成之氨酯壓克力樹脂，且NSP抗菌劑細胞毒性: Ag/NSP ≈ Ag/ZnO/NSP > ZnO/NSP。以JIS Z 2801-2000規範進行抗菌測試，添加75 ppm Ag/NSP、2000 ppm ZnO/NSP及50 ppm Ag/ZnO/NSP之氨酯壓克力樹脂在24小時已對E. faecalis達到99.9 %之抗菌效果，同時由SEM可觀察到E. faecalis在添加50 ppm Ag/NSP之氨酯壓克力樹脂在24小時有被NSP材料物理捕捉的現象。其中添加75 ppm Ag/NSP及50 ppm Ag/ZnO/NSP之氨酯壓克力樹脂不僅具有良好的生物相容性也達到抗菌效果，因此氨酯壓克力與奈米矽片抗菌劑混成材料在未來於臨床治療上之可行性極高。
並列摘要
The purpose of this study is to develop nanoscale silicate/polymer nanocomposite materials for root canal obturation. The main resin, thermoplastic polyurethane (TPU), was synthesized from the CO2/ethylene carbonate (EC) derived polycarbonate polyol (PCPO) as the new oligomer component for enhancing biocompatibility of the TPU. In addition, the previously developed nanoscale silicate platelets (NSP) were introduced into the PCPO-TPU as filler to form the final NSP/TPU composite. The mechanical properties and thermal properties of the NSP/TPU composites were investigated compared to gutta-percha. It was showed that tensile strength and modulus of the NSP/TPU composites can both be much higher than gutta-percha. Enthalpy change of the NSP/PCPO-based TPU composites during phase transition was similar to that of gutta-percha. There is no significant difference in melting point between NSP/TPU composites and gutta-percha. It is found that the new nanocomposite materials of NSP and PCPO-TPU combination have good mechanical, thermal, and antimicrobial properties, and potentials for the root canal obturation cone uses. For sealers, visible-light photopolymerizable urethane-acrylate oligomer was synthesized and blended with dilute monomer (TPGDA) to form UA/TA resin. The mechanical properties, relative molecule weight, viscosities, conversions, curing depth, biocompatibility and antibacterial properties were investigated in this study. The flow of UA/TA (70/30=w/w) resin is the most appropriate through ISO-6876/2001 specifications. Mechanical test shows an optimized value with 3phr CQ+EDMAB in UA/TA resin. Another newly developed germicide, silicate platelets supported nanoparticles (i.e., Ag/NSP, ZnO/NSP, Ag/ZnO/NSP) were introduced into UA/TA resin as filler to form the nanocomposite. Regarding to the biocompatibility issue, the results were shown that the PCPO-involved carbonate-type resin was better than ether-type resin. In combination, the nanocomposites containing 75 ppm Ag/NSP and 50 ppm Ag/ZnO/NSP demonstrated superior antimicrobial efficacy as well as lower immune response, and have great potential in the root canal obturation sealer material.