研發含聚麩胺酸攜帶TGF-β1之鈣矽覆髓材料–材料性質、生物活性及動物實驗

牙髓為具有修復與再生能力之組織，在治療具可回復性的牙髓傷害時，藉由適當的覆髓材料與生長因子，可以誘導牙本質牙髓複合體的再生，形成牙本質橋之屏障阻擋外界刺激並保護剩餘健康的牙髓以保留牙髓的活性。然而目前並沒有一種材料能夠有效地攜帶生長因子，達到理想的覆髓結果。聚麩胺酸(poly-γ-glumatic acid, γ-PGA)為生物相容性良好之高分子聚合物，適合作為藥物之載體，而transforming growth factor -β1 (TGF-β1)具有誘導牙髓細胞分化之能力。而鈣矽材料能提供覆髓材料必要的機械強度與密封能力。本團隊所研發的鈣矽陶瓷材料partial stabilized cement 91 (PSC91)有良好的機械性質及生物活性本實驗將以γ-PGA攜帶TGF-β1，並結合PSC91鈣矽材料，作為覆髓之材料。本實驗γ-PGA加入PSC91 (PSC91/γ-PGA)，以X光繞射分析、硬化時間、抗壓強度、表面微硬度檢測材料性質，並進行體外生物活性、細胞生物相容性與牙髓細胞鹼性磷酸酶檢測，最後以狗作為模型進行動物實驗，觀察micro–computed tomography (μ-CT)影像及組織學切片。結果顯示加入γ-PGA水膠後不太影響PSC91 的水合過程，材料性質在初始硬化時間與抗壓強度的表現皆獲得改善。WST-1 與LDH的結果顯示材料的生物相容性良好，而加入TGF-β1可以促進鹼性磷酸酶的表現。以γ-PGA水膠作為攜帶TGF-β1 的載體在動物實驗中也有優異的表現，其牙本質橋形成的速度較其他組別快。含有γ-PGA之PSC91 結合了鈣矽材料與高分子材料的良好性質，並且具有攜帶藥物之功能。因此含γ-PGA攜帶TGF-β1 之鈣矽覆髓材料相當具有潛力作為活髓治療的材料。

關鍵字

鈣矽陶瓷；活髓治療； TGF-β1 ； γ-PGA ；動物實驗

並列摘要

Dental pulp is able to repair and regenerate itself. To treat the inflamed pulp with healthy pulp tissue inside, incorporating growth factors with appropriate capping materials used in vital pulp therapy can induce dentin-pulp complex regeneration and dentin bridge formation. Therefore, maintaining the vitality of the pulp not only preserves the pulp tissue but blocks out the stimulations from the environment. However, there is no capping materials that can carry growth factors efficiently. With excellent biocompatibility and highly adjustability, poly-γ-glumatic acid (γ-PGA) is suitable candidate for drug carrier. And TGF-β1 is well-known for its ability to induce differentiation of dental pulp. Chemical and mechanical property as well as excellent sealing ability make calcium silicate a well-known capping material. The partial stabilized cement 91 (PSC91) we developed before demonstrated optimal physical properties and bioactivity. The aim of this study was to develop a novel calcium silicate capping material with γ-PGA carrying TGF-β1. Combination of γ-PGA and a modified calcium silicate cement (PSC91/γ-PGA) was tested for hydration, setting time, compressive strength and microhardness. In vitro biocompatibility and bioactivity of PSC91/γ-PGA carrying TGF-β1 were performed, and ALP activity was tested with human dental pulp cells. Moreover, in vivo evaluation was done using a dog animal model by micro-CT radiographic and histological analysis. The results showed that initial setting time and compressive strength were improved by adding γ-PGA hydrogel. Results of WST-1 and LDH revealed that PSC91/γ-PGA containing TGF-β1 was highly biocompatible. Pulp cells treated with PSC91/γ-PGA carrying TGF-β1 showed increased level of ALP activity. In addition, earlier formation of dentin bridge was noted with PSC91/γ-PGA containing TGF-β1 in animal study. We concluded that the novel calcium silicate with γ-PGA carrying TGF-β1 has strong potential as a capping material.

並列關鍵字

calcium silicate ceramics ； vital pulp therapy ； TGF-β1 ； γ-PGA,animal study

參考文獻

李苑玲 (2006). 鈣矽生醫陶瓷在牙髓病治療之研發與應用, 國立台灣大學臨床牙醫學研究所.

黃瑩潔 (2011). 三鈣鋁酸含量對鈣矽陶瓷的材料性質及生物特性之影響, 國立台灣大學牙醫專業學院臨床牙醫研究所.

Accorinte MdLR, Holland R, Reis A, Bortoluzzi MC, Murata SS, Dezan Jr E et al. (2008). Evaluation of Mineral Trioxide Aggregate and Calcium Hydroxide Cement as Pulp-capping Agents in Human Teeth. Journal of Endodontics 34(1):1-6.

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Al-Hezaimi K, Salameh Z, Al-Fouzan K, Al Rejaie M, Tay FR (2011). Histomorphometric and Micro–computed Tomography Analysis of Pulpal Response to Three Different Pulp Capping Materials. Journal of Endodontics 37(4):507-512.

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研發含聚麩胺酸攜帶TGF-β1之鈣矽覆髓材料–材料性質、生物活性及動物實驗

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