State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral, Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, 21201, USA.
Drug Deliv Transl Res. 2019 Feb;9(1):85-96. doi: 10.1007/s13346-018-00600-3.
This represents the first report on the development of metformin-containing dental resins. The objectives were to use the resin as a carrier to deliver metformin locally to stimulate dental cells for dental tissue regeneration and to investigate the effects on odontogenic differentiation of dental pulp stem cells (DPSCs) and mineral synthesis. Metformin was incorporated into a resin at 20% by mass as a model system. DPSC proliferation attaching on resins was evaluated. Dentin sialophosphoprotein (DSPP), dentin matrix phosphoprotein 1 (DMP-1), alkaline phosphatase (ALP), and runt-related transcription factor 2 (Runx2) genes expressions were measured. ALP activity and alizarin red staining (ARS) of mineral synthesis by the DPSCs on resins were determined. DPSCs on metformin-containing resin proliferated well (mean ± SD; n = 6), and the number of cells increased by 4-fold from 1 to 14 days (p > 0.1). DSPP, ALP, and DMP-1 gene expressions of DPSCs on metformin resin were much higher than DPSCs on control resin without metformin (p < 0.05). ALP activity of metformin group was 70% higher than that without metformin at 14 days (p < 0.05). Mineral synthesis by DPSCs on metformin-containing resin at 21 days was 9-fold that without metformin (p < 0.05). A novel metformin-containing resin was developed, achieving substantial enhancement of odontoblastic differentiation of DPSCs and greater mineral synthesis. The metformin resin is promising for deep cavities and perforated cavities to stimulate DPSCs for tertiary dentin formation, for tooth root coatings with metformin release for periodontal regeneration, and for root canal fillings with apical lesions to stimulate bone regeneration.
这是首个关于含二甲双胍牙科树脂开发的报告。目的是利用该树脂作为载体局部递送达格列净以刺激牙源性细胞，促进牙齿组织再生，并研究其对牙髓干细胞（DPSCs）牙源性分化和矿化合成的影响。二甲双胍以 20%的质量分数掺入树脂作为模型体系。评估了附着在树脂上的 DPSCs 的增殖情况。测量了牙本质涎磷蛋白（DSPP）、牙本质基质磷酸蛋白 1（DMP-1）、碱性磷酸酶（ALP）和 runt 相关转录因子 2（Runx2）基因的表达。通过 DPSCs 在树脂上的 ALP 活性和茜素红染色（ARS）测定矿化合成情况。含二甲双胍树脂上的 DPSCs 增殖良好（平均值±SD；n=6），细胞数量从第 1 天到第 14 天增加了 4 倍（p＞0.1）。二甲双胍组的 DSPP、ALP 和 DMP-1 基因表达均显著高于不含二甲双胍的对照组（p＜0.05）。14 天时，二甲双胍组的 ALP 活性比不含二甲双胍组高 70%（p＜0.05）。含二甲双胍树脂上的 DPSCs 的矿化合成在第 21 天是不含二甲双胍组的 9 倍（p＜0.05）。开发了一种新型的含二甲双胍树脂，可显著增强 DPSCs 的成牙本质分化和矿化合成。二甲双胍树脂有望用于深龋和穿孔腔，以刺激 DPSCs 形成第三期牙本质；用于带二甲双胍释放涂层的牙根，以促进牙周再生；用于带根尖病变的根管填充，以刺激骨再生。
