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通过二甲双胍实现牙周和牙根再生的牙科树脂,以增强人牙周膜干细胞的成骨和成牙骨质分化。

Dental resin for periodontal and tooth root regeneration via metformin to enhance osteogenic and cementogenic differentiation of human periodontal ligament stem cells.

作者信息

Yu Kan, Zhu Minjia, Dai Zixiang, Zhang Qinrou, Xiao Le, Li Xinyi, Dai Jialiang, Jia Zihan, Li Jingyi, Bai Yuxing, Zhang Ke

机构信息

Department of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing 100050, China.

Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

出版信息

J Dent. 2025 Feb;153:105507. doi: 10.1016/j.jdent.2024.105507. Epub 2024 Dec 4.

DOI:10.1016/j.jdent.2024.105507
PMID:39643264
Abstract

OBJECTIVES

This study developed a novel dental resin incorporating metformin to repair root caries and periodontitis defects. The objectives were to: (1) Develop a novel dental resin with metformin release to fulfill the clinical requirements for mechanical properties; and (2) investigate the metformin release pattern and the effects on osteogenic and cementogenic differentiation of human periodontal ligament stem cells (hPDLSCs).

METHODS

Resin specimens with different concentrations of metformin were fabricated. Metformin release was measured using high-performance liquid chromatography. Cellular growth and proliferation on resin were assessed. Alizarin red S staining and an alkaline phosphatase (ALP) activity were determined. Quantitative real-time reverse transcription PCR was employed to determine osteogenic and cementogenic differentiation.

RESULTS

The resin with 7.5 % metformin had mechanical properties comparable to those of a commercial control, thus satisfying the clinical requirements (mean ± SD; n = 10). hPDLSCs showed robust growth and proliferation on resin. At 14 days, the number of hPDLSCs increased by four-fold (p > 0.1). ALP activity in the metformin group was 1.8 times higher than that of control (p < 0.05). At 21 days, the metformin group showed a significant increase in mineral synthesis. Metformin group had cementogenic and osteogenic differentiation values that were 2.5 and 2.3 times higher, respectively, than control without metformin (p < 0.05).

SIGNIFICANCE

A metformin-resin was formulated that greatly promoted both cementogenic and osteogenic differentiation for the first time. This resin was mechanically strong and supported hPDLSC adhesion, growth and proliferation. This resin substantially enhanced hPDLSC osteogenic and cementogenic differentiation, yielding mineral synthesis of hPDLSCs more than 2-fold that of control without metformin. This new metformin-resin shows promise for the restoration of tooth root caries and the regeneration of periodontal tissues including alveolar bone and cementum.

摘要

目的

本研究开发了一种新型含二甲双胍的牙科树脂,用于修复根龋和牙周炎缺损。目标如下:(1)开发一种能释放二甲双胍的新型牙科树脂,以满足机械性能的临床要求;(2)研究二甲双胍的释放模式及其对人牙周膜干细胞(hPDLSCs)成骨和成牙骨质分化的影响。

方法

制备了不同浓度二甲双胍的树脂标本。采用高效液相色谱法测定二甲双胍的释放量。评估树脂上细胞的生长和增殖情况。进行茜素红S染色和碱性磷酸酶(ALP)活性测定。采用定量实时逆转录PCR法测定成骨和成牙骨质分化情况。

结果

含7.5%二甲双胍的树脂的机械性能与市售对照相当,满足了临床要求(平均值±标准差;n = 10)。hPDLSCs在树脂上显示出强劲的生长和增殖。14天时,hPDLSCs的数量增加了四倍(p > 0.1)。二甲双胍组的ALP活性比对照组高1.8倍(p < 0.05)。21天时,二甲双胍组的矿物质合成显著增加。二甲双胍组的成牙骨质和成骨分化值分别比不含二甲双胍的对照组高2.5倍和2.3倍(p < 0.05)。

意义

首次制备出一种能极大促进成牙骨质和成骨分化的含二甲双胍树脂。这种树脂机械强度高,支持hPDLSC的黏附、生长和增殖。该树脂显著增强了hPDLSC的成骨和成牙骨质分化,使hPDLSCs的矿物质合成比不含二甲双胍的对照组增加了2倍多。这种新型含二甲双胍树脂有望用于牙根龋的修复以及包括牙槽骨和牙骨质在内的牙周组织的再生。

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3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats.3D打印微纤维在具有三培养和两阶段二甲双胍释放功能的支架中包裹干细胞,用于大鼠骨/血管/神经再生。
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