The average composite dental restoration fails within 5-7 years. The primary cause of failure is at the interface between tooth structure and the restoration, and frequently results in secondary caries. Replacement of the restoration requires the removal of the old, increased loss of tooth structure, increased cost, and a decreased prognosis for the tooth. Despite extensive advances in restorative materials, success in improving the dentin-resin interface and minimizing replacement of restorations has been limited to changes to the material itself. The ultimate goal of this proposal is to develop new methods to improve dentin matrix strength and stability, and thereby enhance the durability of dentin-resin restorations. Preliminary studies provide strong support for nature-derived agents, in particular polyphenol-rich plant extracts, which strongly enhance dentin matrix properties and positively impact the dentin-resin bonds. These agents are proposed as """"""""biomodifiers"""""""" of dentin matrix. This innovative approach to the clinical challenge may open new perspectives for restorative/reparative therapies of lost tooth structure. The demonstrated increase in dentin strength appears to involve interactions between dentin organic components and a family of phytoconstituents, the oligomeric proanthocyanidins (OPCs). OPCs are broadly used as natural antioxidants and have proven to be safe in various clinical applications and in herbal dietary supplements. This multidisciplinary project will focus on the biochemistry and biomechanics involved in the multi-functional interactions between OPC and major dentin matrix components, and investigates parameters involved in the formation and sustainability of dentin- resin bonds. To this end, the main hypothesis is that multi-functional interactions between the """"""""biomodifiers"""""""" and dentin matrix components enhance the dentin matrix and result in quality improvement of the dentin-resin interface. In addition, phytochemical isolation and characterization of the bioactive ingredients of OPC-rich plant extracts will lead to a better understanding of the mechanisms of interaction with the dentin matrix. Combined results will enable optimization of desirable dentin activity and standardization of an interventional material for potential clinical application.
The Specific Aims are:
Aim 1 - Standardization of an OPC-rich natural extract with defined dentin matrix activity by means of modern phytochemical analysis;performed in tandem with Aim 2 - Determination of the short- and long-term interactions of bioactive polyphenols/OPC with the organic dentin matrix (collagen, proteoglycans, matrix metalloproteinases), as it relates to strength and stability of the tissue.
Aim 3 - Establishment of clinical applicability of a standardized interventional material using in vitro models to determine both short and long-term restorative/reparative benefits of dentin biomodification. The project represents an inter-disciplinary (dentistry, pharmacy) and innovative approach to strengthening the dentin matrix substrate for restorative procedures. The outcome has potential to produce longer-lasting composite restorations, which can ultimately improve health care and reduce health care costs.

Public Health Relevance

Biomodification of tooth structure is proposed as a new method to enhance the strength and stability of the dentin matrix. This approach utilizes natural products to generate a more suitable dentin substrate for restorative procedures. The multi-functional interactions of complex polyphenolic natural products, particularly oligomeric proanthocyanidins, with major dentin matrix components will be studied in order to identify the bioactive ingredients, maximize desirable dentin activity, and standardize a material for potential clinical application. The long-term goal is to enhance dentin matrix strength and improve the durability of dental restorations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE021040-03
Application #
8525113
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Wan, Jason
Project Start
2011-09-01
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$339,120
Indirect Cost
$123,120
Name
University of Illinois at Chicago
Department
Dentistry
Type
Schools of Dentistry
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
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Cecchin, D; Farina, A P; Vidal, Cmp et al. (2018) A Novel Enamel and Dentin Etching Protocol Using ?-hydroxy Glycolic Acid: Surface Property, Etching Pattern, and Bond Strength Studies. Oper Dent 43:101-110
Kulakowski, Daniel; Leme-Kraus, Ariene A; Nam, Joo-Won et al. (2017) Oligomeric proanthocyanidins released from dentin induce regenerative dental pulp cell response. Acta Biomater 55:262-270
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de Mattos Pimenta Vidal, Cristina; Leme-Kraus, Ariene Arcas; Rahman, Momina et al. (2017) Role of proteoglycans on the biochemical and biomechanical properties of dentin organic matrix. Arch Oral Biol 82:203-208
Yourdkhani, Mostafa; Leme-Kraus, Ariene Arcas; Aydin, Berdan et al. (2017) Encapsulation of grape seed extract in polylactide microcapsules for sustained bioactivity and time-dependent release in dental material applications. Dent Mater 33:630-636
Liu, Yang; Friesen, J Brent; Grzelak, Edyta M et al. (2017) Sweet spot matching: A thin-layer chromatography-based countercurrent solvent system selection strategy. J Chromatogr A 1504:46-54
Leme-Kraus, A A; Aydin, B; Vidal, C M P et al. (2017) Biostability of the Proanthocyanidins-Dentin Complex and Adhesion Studies. J Dent Res 96:406-412
Nam, Joo-Won; Phansalkar, Rasika S; Lankin, David C et al. (2017) Absolute Configuration of Native Oligomeric Proanthocyanidins with Dentin Biomodification Potency. J Org Chem 82:1316-1329
Vidal, Cristina M P; Zhu, Weiying; Manohar, Suresh et al. (2016) Collagen-collagen interactions mediated by plant-derived proanthocyanidins: A spectroscopic and atomic force microscopy study. Acta Biomater 41:110-8

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