碳酸鈣中孔洞鈣矽材料與磷酸混合製劑於牙本質小管內的通透性及再結晶機制

Mechanism of Ion Permeability & Recrystallization of CaCO3@ Mesoporous Silica-Phosphate in Dentinal Tubules

溫如琳(Ju-Lin Wen)

指導教授 ： 林俊彬

共同指導教授 ： 林弘萍(Hong-Pin Lin)

國立臺灣大學/牙醫專業學院/臨床牙醫學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.00924

摘要

牙本質敏感症的治療截至目前，仍沒有一個令人滿意的臨床結果，本團隊之前的研究顯示以明膠為模板的含碳酸鈣中孔洞二氧化矽複合材料 (簡稱中孔洞鈣矽材料，GCMS) 與30%磷酸調拌，可以在10分鐘內，有效地阻塞牙本質小管達30 μm，並且不會對牙齒造成酸蝕破壞，具有應用於臨床，治療牙本質敏感症極大的潛力。細胞毒性實驗證實，中孔洞鈣矽材料的材料萃取液及中孔洞鈣矽材料/磷酸製劑經過牙本質屏障有好的細胞活性，而中孔洞鈣矽材料/磷酸製劑的材料萃取液則有較高的細胞毒性。
本團隊之前離子層析儀及Transwell dentin disc model的結果，氫氧化鈣/去離子水製劑不會經由0.2 mm的牙本質屏障釋放出鈣離子，而中孔洞鈣矽材料/磷酸溶液則能經由0.2 mm的牙本質屏障釋放出鈣離子及磷酸根離子，可初步推測中孔洞鈣矽材料/磷酸製劑形成沉澱結晶的機制：酸性提高而使電勢能提高，對於鈣離子產生引力，使鈣離子進入牙本質小管，而後由於牙齒有緩衝的作用，pH值升高形成沉澱結晶。
但做為一個理想的牙科臨床治療材料，30%磷酸在臨床試驗的實行上有其困難，生物相容性更是不可忽視的問題，並且本團隊希望進一步了解其在牙本質小管內沉澱結晶的機制，並了解牙本質小管對於離子的通透性及選擇性，以使未來能更容易將治療藥物帶入牙本質小管及牙髓神經。
因此，本研究的目的是：
1. 找出影響牙本質小管通透性的因素，及牙本質小管是否有離子選擇性？
2. 找出是否有其它材料能替代原本的30%磷酸配方，一樣能達到阻塞牙本質小管的效果，並期待有更好的生物相容性。
3. 證實本團隊的GCMS材料，在使用後能增加牙本質硬度。
第一部分，以New Transwell dentin disc model及離子層析儀確認0.5 M磷酸二氫鉀溶液，0.5 M氯化鈣溶液，及GCMS/30%磷酸製劑經由0.25 mm牙齒滲透所釋放的陰陽離子濃度。接著，再用SEM觀察這些牙本質試片。
第二部分，以GCMS和磷酸二氫鈉溶液，磷酸二氫鉀溶液，及調整過pH值的磷酸二氫鉀溶液以不同比例混合；或以本團隊和西德有機醫藥生技公司合作製成的GCMS paste及磷酸二氫鈉paste以不同比例混合，再分成不同天數組別，塗抹在牙本質試片上，用SEM觀察其成效。
第三部分，以GCMS和30%磷酸製劑以粉液比1：2混合，並塗抹在牙本質試片上三次，第三次以pH值9的鹼性水使其沈澱。之後再以硬度計測試牙本質的硬度是否有增加。
結論：(1) 牙本質小管的各離子通透性在酸性環境下較好。(2) 在中性與酸性環境下，正電荷離子在此TW DD model較負電荷離子易於通過牙本質小管。(3) 在此TW DD model，當離子整個帶電價數較高時，通過速度也較快。(4) 磷酸二氫鈉比起磷酸二氫鉀更適合取代之前的30%磷酸，與GCMS混合，以治療牙本質過敏症。(5) 除了適當的pH值，材料本身的鈣磷莫耳濃度比對於牙本質小管的再結晶作用亦是重要的。(6) GCMS與30﹪磷酸的混合製劑，塗抹在牙本質上，可增加牙本質的硬度，也可能提高抗刷耗的功能。

關鍵字

中孔洞 ； 牙本質敏感症 ； 牙本質小管選擇性及通透性 ； 磷酸根及鈣離子

並列摘要

Dentin hypersensitivity is a common encountered chief complaint for dental general practitioner, but it is also a troublesome issue. Our previous study showed that gelatin-templated calcium mesoporous silicate (GCMS) with 30% H3PO4 could efficiently occlude dentinal tubules by precipitation thus have great potential in treating dentin hypersensitivity. Also, GCMS with 30% H3PO4 could show great biocompatibility through dentin disc barrier and other comparisans obtain similar results. The transwell dentin disc model and ion chromatography revealed that calcium hydroxide with deionized water would not release calcium ion through 0.2 mm dentin disc. In contrast, GCMS with 30% H3PO4 could obtain phosphoric acid and calcium.
Therefore, research goals of the present study is:
1. To find out the factors that affect ion permeability & selectivity in dentinal tubules.
2. To find a replacement for 30% H3PO4.
3. To prove our material can increase microhardness of dentin.
This research comprised of three parts. First, we assess the differences of ion permeability and selectivity through dentin disks between pH value, ionic charge, valence electron.
The second part investigated the obturating effects in dentinal tubules of NaH2PO4 and KH2PO4 saturated solution when they are replaced the original 30% H3PO4 and mixed with GCMS. Futherly, our group fabricated a paste that include GCMS and NaH2PO4, then we also evaluate the obturating effects in dentinal tubules of the mixture.
In the third part, we estimated the microhardness of the dentin surface before and after applying GCMS/30% H3PO4 mixture. If the application of materials can increase the hardness of dentin, it may also raise up the possibility of anti-abrasion.
In conclusion：(1) Ion permeability is better in acidic condition. (2) Positive charge passes dentinal tubules easier in acidic & neutral condition than negative charge at this model. (3) When there are more valence electrons, the ions may pass the dentinal tubules easier. (4) According to their obturated effects, NaH2PO4 is a better replacement for H3PO4 than KH2PO4. (5) Other than pH gradient, Ca2+/PO43- ratio is also important in recrystallization at dentinal tubules. (6) GCMS/H3PO4 mixture can increase microhardness of dentin.

並列關鍵字

Mesoporous ； dentin hypersensitivity ； dentin tubules selectivity and permeability ； calcium and phosphate ion

參考文獻

Abe T, Taguchi, A., & Iwamoto, M. (1995). Non-silica-based mesostructured materials. 1. Synthesis of vanadium oxide-based materials. Chemistry of materials 7(8):1429-1430.

Absi EG, Addy M, Adams D (1987). Dentine hypersensitivity. A study of the patency of dentinal tubules in sensitive and non-sensitive cervical dentine. Journal of clinical periodontology 14(5):280-284.

Absi EG, Addy M, Adams D (1989). Dentine hypersensitivity. The development and evaluation of a replica technique to study sensitive and non-sensitive cervical dentine. Journal of clinical periodontology 16(3):190-195.

Addy M, Absi EG, Adams D (1987). Dentine hypersensitivity. The effects in vitro of acids and dietary substances on root-planed and burred dentine. Journal of clinical periodontology 14(5):274-279.

Addy M, Urquhart E (1992). Dentine hypersensitivity: its prevalence, aetiology and clinical management. Dental update 19(10):407-408, 410-402.