2014-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647788摘要：活髓治療的目的在使牙髓保持活性並形成修復牙本質，維持牙齒正常生理結構及功能。根據本研究團隊之研究結果顯示，特殊製程的磷酸鈣(CPC)與硫酸鈣 (CSC)雙相鈣基複合材料可有效改善各自於臨床應用之缺點。但是不管是 CPC 或是 CSC 只要植入體內後，就要面臨被纖維組織包覆以至於牙髓細胞難以接觸及進入材料內部等問題，這些情況都會讓牙髓再生的成功率下降。添加膠原蛋白酶(Collagenase)可將周圍細胞外基質移除，使更多細胞能游離出，並促使之回到前驅細胞的狀態。Statin 類藥物因為具有刺激 BMP-2 mRNA 的機轉，此機轉可以進一步啟動 Dspp（Dentin Sialophosphoprotein）mRNA 的表現，而 Dspp 為修復性牙本質生成之關鍵媒介。因此本研究將利用 CPC 與 CSC 的降解時間不同，於牙髓暴露區域形成具有空洞的細胞支架，再搭配膠原蛋白酶與 Simvastatin 的釋放，結合成具功能性之活髓治療生醫材料。本研究計畫分三年：第一年目標為含膠原蛋白酶及 Simvastatin 的生醫陶瓷之製備，並分析不同組成比例的基本物理、化學與機械性質；接著第二年進行體外實驗及小動物實驗模式，將篩選出所製備之複合生醫陶瓷之最佳組合，確認其具有良好之生物相容性及鈣化誘導能力；第三年將以大動物實驗探討牙髓修復再生機制，並驗證本材料於牙髓牙本質再生的成效。未來更可將本計畫所研發的材料系統及研究架構應用於其他組織修復機制的探討與生醫材料的改良。 <br> Abstract: Vital pulp therapy is to preserve the pulp vitality as well as to form the reparative dentin for maintaining the normal physical structures and functions of teeth. According to the preliminary results from our research team, specific processed biphasic calcium based composite cements could improve the drawbacks of calcium phosphate ceramics (CPC) and calcium sulfate ceramics (CSC) individually in clinical application. However, CPC or CSC will be encapsulated by the fibrous tissue once implanted and lead to the difficulties for pulp cells to react and enter the inner part of the materials. In such situation, the successful rate of vital pulp therapy will be decreased. The external matrix from the surrounding cells can be removed by adding collagenase, and allows the cells to move freely and induce them to return to the progenitor state. The Statins group has the ability to stimulate the mechanism of BMP-2 mRNA, and could further initiate the performance of Dspp （ Dentin Sialophosphoprotein）mRNA which is a crucial medium to form reparative dentin. Accordingly, this study will develop novel biphasic composite cements containing collagenase and Simvastatin for vital pulp therapy, which utilize the different degradation behaviors of CPC and CSC to form porous cellular scaffold. This project has been arranged for three years, and the specific aims are as follows: In the first year, in order to prepare the biomedical ceramics containing collagenase and Simvastatin, we aim to test the physical, chemical and mechanical properties of different ratios and compositions of biphasic composite cements. In the second year, we aim to carry out the in vitro experiments and small animal tests, which will sort out the best combinations of the materials, validate the excellent performance of biocompatibility and calcifying ability. In the last year, we will probe into the pulp-dentin regeneration mechanism through large animal experiments, and also verify the regenerate efficiency of the test materials. The goal of this project is to understand the mechanisms underlying pulp-dentin regeneration and test the efficacy in vivo of our materials for vital pulp therapy. The outcome of this study could also be applied to improve the biomaterials for tissue regeneration in the future.活髓治療磷酸鈣陶瓷硫酸鈣陶瓷膠原蛋白酶SimvastatinVital pulp therapyCalcium phosphate ceramicsCalcium sulfate ceramicsCollagenaseSimvastatin