Galloylated proanthocyanidins in dentin matrix exhibit biocompatibility and induce differentiation in dental stem cells.

IF 2.1 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Daniel Kulakowski, Rasika M Phansalkar, Ariene A Leme-Kraus, James McAlpine, Shao-Nong Chen, Guido F Pauli, Sriram Ravindran, Ana K Bedran-Russo
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引用次数: 0

Abstract

Aim: Grape seed extract contains a complex mixture of proanthocyanidins (PACs), a plant biopolymer used as a biomaterial to improve reparative and preventive dental therapies. Co-polymerization of PACs with type I collagen mechanically reinforces the dentin extracellular matrix. This study assessed the biocompatibility of PACs from grape seed extract on dental pulp stem cells (DPSCs) in a model simulating leaching through dentin to the pulp cavity. The aim was to determine the type of PACs (galloylated vs. non-galloylated) within grape seed extract that are most compatible with dental pulp tissue.

Methodology: Human demineralized dentin was treated with selectively-enriched dimeric PACs prepared from grape seed extract using liquid-liquid chromatography. DPSCs were cultured within a 2D matrix and exposed to PAC-treated dentin extracellular matrix. Cell proliferation was measured using the MTS assay and expression of odontoblastic genes was analyzed by qRT-PCR. Categorization of PACs leaching from dentin was performed using HPLC-MS.

Results: Enriched dimeric fractions containing galloylated PACs increased the expression of certain odontoblastic genes in DPSCs, including Runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor (VEGF), bone morphogenetic protein 2 (BMP2), basic fibroblast growth factor (FGF2), dentin sialophosphoprotein (DSPP) and collagen, type I, alpha 1 (COLI). Galloylated dimeric PACs also exhibited minor effects on DPSC proliferation, resulting in a decrease compared to control after five days of treatment. The non-galloylated dimer fraction had no effect on these genes or on DPSC proliferation.

Conclusions: Galloylated PACs are biocompatible with DPSCs and may exert a beneficial effect on cells within dental pulp tissue. The observed increase in odontoblastic genes induced by galloylated PACs together with a decrease in DPSC proliferation is suggestive of a shift toward cell differentiation. This data supports the use of dimeric PACs as a safe biomaterial, with galloylated dimeric PACs exhibiting potential benefits to odontoblasts supporting dentin regeneration.

Abstract Image

牙本质基质中没食子酸原花青素表现出生物相容性并诱导牙干细胞分化。
目的:葡萄籽提取物含有原花青素(PACs)的复杂混合物,原花青素是一种植物生物聚合物,用于改善修复和预防性牙科治疗的生物材料。pac与I型胶原蛋白的共聚合在机械上强化了牙本质细胞外基质。本研究通过模拟牙本质浸出到牙髓腔的模型,评估了葡萄籽提取物pac在牙髓干细胞(DPSCs)上的生物相容性。目的是确定葡萄籽提取物中与牙髓组织最相容的pac类型(没食子酸与非没食子酸)。方法:采用液-液色谱法,用葡萄籽提取物制备的选择性富集二聚体PACs处理人脱矿牙本质。DPSCs在二维基质中培养,并暴露于pac处理的牙本质细胞外基质中。MTS法检测细胞增殖,qRT-PCR法检测成牙细胞基因表达。采用高效液相色谱-质谱法对牙本质浸出的PACs进行分类。结果:富含没食子酸化PACs的二聚体组分增加了DPSCs中某些成牙细胞基因的表达,包括runt相关转录因子2 (RUNX2)、血管内皮生长因子(VEGF)、骨形态发生蛋白2 (BMP2)、碱性成纤维细胞生长因子(FGF2)、牙本质唾液磷蛋白(DSPP)和I型α 1胶原(COLI)。没食子酸二聚体PACs对DPSC的增殖也有轻微的影响,治疗5天后,与对照组相比,PACs的增殖有所减少。非没食子酸二聚体部分对这些基因或DPSC增殖没有影响。结论:没食子酸化PACs与DPSCs具有生物相容性,并可能对牙髓组织细胞产生有益作用。经观察,没食子酸化PACs诱导的成牙细胞基因增加,同时DPSC增殖减少,提示了向细胞分化的转变。这些数据支持二聚体pac作为一种安全的生物材料的使用,没食子酸二聚体pac显示出支持牙本质再生的成牙细胞的潜在益处。
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来源期刊
Journal of Bioactive and Compatible Polymers
Journal of Bioactive and Compatible Polymers 工程技术-材料科学:生物材料
CiteScore
3.50
自引率
0.00%
发文量
27
审稿时长
2 months
期刊介绍: The use and importance of biomedical polymers, especially in pharmacology, is growing rapidly. The Journal of Bioactive and Compatible Polymers is a fully peer-reviewed scholarly journal that provides biomedical polymer scientists and researchers with new information on important advances in this field. Examples of specific areas of interest to the journal include: polymeric drugs and drug design; polymeric functionalization and structures related to biological activity or compatibility; natural polymer modification to achieve specific biological activity or compatibility; enzyme modelling by polymers; membranes for biological use; liposome stabilization and cell modeling. This journal is a member of the Committee on Publication Ethics (COPE).
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