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Galloylated proanthocyanidins in dentin matrix exhibit biocompatibility and induce differentiation in dental stem cells
Journal article   Open access   Peer reviewed

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

Daniel Kulakowski, Rasika M Phansalkar, Ariene A Leme-Kraus, James B McAlpine, Shao-Nong Chen, Guido F Pauli, Sriram Ravindran and Ana K Bedran-Russo
Journal of bioactive and compatible polymers, Vol.37(3), pp.220-230
05/2022
DOI: 10.1177/08839115221095154
PMCID: PMC10353770
PMID: 37465414
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC10353770/pdf/nihms-1857444.pdfView
Open Access

Abstract

Grape seed extract contains a complex mixture of proanthocyanidins (PACs), a class of plant biopolymers that can be 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. 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. 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 5 days of treatment. The non-galloylated dimer fraction had no effect on these genes or on DPSC proliferation. Galloylated PACs are biocompatible with DPSCs and may even 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.

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