Development of new sol-gel tricalcium silicate cements in endodontic applications

根尖逆充填、根管穿孔修補以及活髓治療是臨床牙髓病治療常見的術式，而這些術式都需要使用適當的修補材料將缺損的齒質或修形的窩洞進行填補與修復。而目前臨床上所使用的材料很多，但或多或少都有缺點存在，並無法完全符合理想材料之標準。其中以鈣矽酸鹽為主成分的Mineral trioxide aggregate (MTA)，因具有生物相容性、生物活性、封閉性質佳等優點，為目前最普遍使用的材料。但是MTA硬化時間過長、操作性質不佳與可能含有有毒物質卻是臨床應用的重大缺點。研究顯示MTA良好的生物相容性、生物活性以及封閉能力，可能與其主要成分鈣矽酸鹽的性質表現有關，然而根據本團隊先前的研究顯示，鈣矽酸鹽的水合速度較慢而有硬化時間較長的問題。因此本研究以三鈣矽酸鹽為出發點，應用溶膠-凝膠製程反應效率佳與產物純度高的特性，以改善材料硬化時間過長的問題，進而研發理想的牙髓病修補材料。本實驗分為兩個部分，首先利用溶膠-凝膠法備製三鈣矽酸鹽，並比較與市售MTA在物理化學與臨床性質的表現，以評估溶膠-凝膠製程之三鈣矽酸鹽在臨床應用的潛力。結果發現，以溶膠-凝膠製程三鈣矽酸鹽粉末（sol-gel C3S, sC3S）與高溫燒結製成的三鈣矽酸鹽粉末（Ｃ3S）相比較，兩者產物晶相的X光繞射峰出現的位置大致相同；而在進行水合反應後，除了與反應物相關的繞射峰強度有下降消失的情況外，同時也有代表反應產物的氫氧化鈣與碳酸鈣的繞射峰出現。此外隨著水合反應時間的增加，兩者的水合產物均從鬆散具有空隙的結構，逐漸轉變為緻密的結晶構造。電子顯微鏡觀察結果顯示，sC3S粉末顆粒較小且表面具有孔洞性；由於其高表面積特性，因此在硬化時間方面使得sC3S (12±0.8min)相較於C3S (177±10min)以及市售的白色MTA (WMTA:172±8min)和灰色MTA (GMTA: 114±5min)有大幅降低，在臨床應用上具有意義。而在牙本質之抗推離鍵結強度方面，sC3S (12.96±4.1 MPa)與C3S (11.11±3.9MPa)、WMTA (16.2±4.5 MPa) 、GMTA (15.78±3.8 MPa)無顯著差異。但是以此溶膠-凝膠製成的三鈣矽酸鹽仍有殘存氧化鈣過高與抗壓強度較差 (20.21±3.26 MPa)等問題，因此在第二部分，我們藉著改變製程中混合順序( r值)與催化劑濃度，來改善材料的物理化學與臨床性質。結果顯示，改變反應r值與催化劑濃度並不會改變產物粉末的孔洞性質，同時也不會影響到製程產物的晶相種類，但是會造成氧化鈣相關的繞射峰強度有明顯下降的效應。此外，隨著催化劑濃度降低，水合產物表面結晶形態會逐漸由條柱狀晶體發展成立體堆疊的片狀結晶；同時隨著水合反應時間增加，其顯微結構也有逐漸緻密的趨勢。在硬化時間方面，與第一部分的溶膠-凝膠製程產物相比，改變反應r值與催化劑濃度會使得產物的硬化時間增加 (28min~34min)，但仍明顯短於市售兩種MTA (p<0.001)；同時降低催化劑濃度可使產物具有較高的抗壓強度 (68.14±7.12MPa)，與市售材料MTA相較，其差異具統計學上的意義 (p<0.001)。綜合本研究結果，溶膠-凝膠製程可製備具有表面孔洞性的三鈣矽酸鹽，其水合行為與產物與高溫燒結之三鈣矽酸鹽相似，但其硬化時間可短至12分鐘，於臨床應用具有意義。而降低溶膠-凝膠製程的起始r值與催化劑濃度，雖然對於牙本質推離鍵結強度沒有明顯的影響，但可促進材料的膠化行為，降低氧化鈣殘存量或結晶性以提升產物純度，同時也可提高水合產物的抗壓強度，在臨床牙髓病修補治療應用上深具潛力。An ideal repair material plays an important role in the success of endodontic repair therapy including retrograde filling, perforation repair and vital pulp therapy. There are many repair materials have been used in endodontic applications, but none of these could fit the requirements of ideal material. Mineral trioxide aggregate (MTA) has been currently considered as a potential material used in endodontic repair treatments with promising results, which may caused by its major component - the tricalcium silicate (C3S). However, several disadvantages of MTA have been reported such as long setting time, difficulty in handling, and the high arsenic levels contained. Calcium silicate ceramics (CSCs) without toxic ingredients, developed by our research team, are surface bioactive ceramics presenting the similar behaviors in hydration, cell-material interaction and bioactivity to MTA. But the large amount of CaO remained in the high temperature sintering CSCs caused the low chemical reactivity and long setting time. In this study, we developed the porous C3S to enhance their setting reaction by applying sol-gel process, and further investigated their potential using in endodontic applications. This study was conducted to two sections. In the first section, we synthesized tricalcium silicate via sol-gel process (sC3S) following Tsai’s protocol, and evaluated its physical-chemical and clinical properties with commercial MTA and conventional-sintered C3S as compared groups. The results of X-ray diffraction (XRD) analysis showed the similar patterns in sC3S and C3S powders. After hydrated, peaks corresponding to reactants decreased, and peaks corresponding to hydration products of calcium hydroxide and calcium carbonate were recorded by XRD in both groups. Furthermore, the microstructures of C3S and sC3S hydrates were similar, which became more compact structure when time increased. Scanning electron microscope indicated the smaller particle size and porous texture of sC3S powder. In addition, sC3S presented the significant short setting time (12±0.8min) than those of C3S (177±10min), WMTA (172±8min) and GMTA (114±5min) gourps. In the push-out bonding test, there was no significant difference between sC3S (12.96±4.1 MPa), C3S (11.11±3.9MPa), WMTA (16.2±4.5 MPa) and GMTA (15.78±3.8 MPa). To consider the high level content of residual calcium oxide and unacceptable compressive strength (20.21±3.26 MPa) of previous synthesized sC3S, the protocols of sol-gel process were be modified by changing the mixing order (r ratio) and the concentration of catalyst to improve the properties of the material in the second section. The results showed that the changes in r ratio and the concentration of catalyst would not affect the porous texture and crystal phases of the produced sC3S powder, except the decline of the intensities of the peaks corresponded to calcium oxide. After hydration, the crystals over the outer surface changed their shapes form bar-like crystals to plate-like crystals with 3D structure when the catalyst decreased in concentration. In comparison to the previous synthesized sC3S in first section, the modification of sol-gel process by changing the r ratio and the concentration of catalyst would slightly prolong the setting time of products (28min~34min), but still significantly shorter than that of commercial MTA (p<0.001). Meanwhile, the decrease of the concentration of catalyst in sol-gel process would also improve the compressive strength of products (68.14±7.12MPa), which was much better than that of MTA (p