Journal article
Oligomeric proanthocyanidins released from dentin induce regenerative dental pulp cell response
Acta biomaterialia, Vol.55, pp.262-270
06/2017
DOI: 10.1016/j.actbio.2017.03.051
PMCID: PMC5504470
PMID: 28365481
Abstract
[Display omitted]
Proanthocyanidins (PACs) are plant-derived, multifunctional compounds that possess high interactivity with extracellular matrix (ECM) components. The documented affinity of PACs for type-I collagen is directly correlated with their structural features and degree of polymerization. In this investigation, centrifugal partition chromatography (CPC) was used to sequentially deplete less active monomeric and polymeric PACs from a crude Pinus massoniana bark extract to create refined mixtures enriched in oligomeric PACs. The ability of these oligomeric PACs to modify the mechanical properties of the dentin collagen matrix and their biocompatibility with dental pulp cells (DPCs) was evaluated in an innovative biomimetic environment. The refined mixtures displayed high interactivity with dentin collagen as demonstrated by a significant increase (>5-fold) in the modulus of elasticity of the dentin matrix. In a simplified model of the dentin-DPC complex, DPCs embedded within their native ECM in the presence of PAC-treated dentin exhibited increased proliferation. Quantitative gene expression analyses indicated that exposure to PAC-treated dentin increased the expression of key biomineralization and odontogenic differentiation regulators, including RUNX2, BMP2, OCN, and DSPP. LC-MS/MS analysis revealed that PACs two to four units long (dimers, trimers, and tetramers) were being released from dentin into media, influencing cell behavior. Overall, the results suggested that PAC dimers, trimers, and tetramers are not only biocompatible, but enhance the differentiation of DPCs towards a phenotype that favors biomineralization. PAC-enriched refined mixtures can influence the field of biomaterials and regeneration by serving as renewable, non-cytotoxic agents that can increase the mechanical properties of biomaterials.
Pine bark extract is a renewable source of structurally diverse proanthocyanidins (PACs), multifunctional compounds whose interaction with collagen can be tailored to specific purposes by enrichment of selected PACs from the complex mixture. Oligomeric PACs were enriched from the extract and were shown here to sustain desired tissue modification and were thus assessed for cellular response in a model of the dentin-pulp interface. This model was developed to mimic leaching of potentially reactive compounds into pulp tissue. Dental pulp cells exposed to PAC-treated dentin showed increased proliferation and expression of genes necessary for extracellular matrix deposition and biomineralization, processes crucial for forming new dentin. Thus, collagen-interactive PACs may also enhance tissue regeneration and have broad impact in tissue engineering.
Details
- Title: Subtitle
- Oligomeric proanthocyanidins released from dentin induce regenerative dental pulp cell response
- Creators
- Daniel Kulakowski - University of Illinois at ChicagoAriene A. Leme-Kraus - University of Illinois at ChicagoJoo-won Nam - University of Illinois at ChicagoJames McAlpine - University of Illinois at ChicagoShao-Nong Chen - University of Illinois at ChicagoGuido F. Pauli - University of Illinois at ChicagoSriram Ravindran - University of Illinois at ChicagoAna K. Bedran-Russo - University of Illinois at Chicago
- Resource Type
- Journal article
- Publication Details
- Acta biomaterialia, Vol.55, pp.262-270
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.actbio.2017.03.051
- PMID
- 28365481
- PMCID
- PMC5504470
- ISSN
- 1742-7061
- eISSN
- 1878-7568
- Grant note
- DOI: 10.13039/100000072, name: NIDCR; DOI: 10.13039/100000002, name: NIH
- Language
- English
- Date published
- 06/2017
- Academic Unit
- Operative Dentistry
- Record Identifier
- 9984367725002771
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