Out of 166 million restorations placed in the U.S., clinical data suggest that >100 million were replacements. Replacement therapy is expected to increase with the growing demand for composite restorations, e.g. as indicated in the 2009-2013 NIDCR strategic plan, dental composites have an average replacement time of 5.7 years. The NIDCR strategic plan stresses the development of longer-lasting restorations and research that explores whether oral biofilms accelerate the degradation of dental composites, leading to secondary decay and restoration failure. The gingival margin of composite restorations is particularly vulnerable to decay and at this margin, the adhesive and its seal to dentin provides the primary barrier between the prepared tooth and the environment. Adhesion of the cariogenic bacterium, Streptococcus mutans, to surfaces in the mouth creates an environment that supports the subsequent attachment and growth of other bacterial species, ultimately forming a micro-ecosystem, i.e., a biofilm. Dental plaque biofilm cannot be eliminated, but the pathogenic impact of the biofilm at the gingival margin could be reduced by engineering novel anti-cariogenic dentin adhesives. We propose a twofold strategy to develop adhesives that (i) limit attachment of the glycoprotein, gp340, that mediates adhesion of S. mutans and (ii) neutralize the acidic micro-environment to prevent demineralization of the adjacent tooth structure. The overall hypothesis of this work is that methacrylate-based adhesives formulated to minimize gp340/S. mutans attachment and to neutralize the acidic micro-environment will provide an enhanced barrier to cariogenesis as compared to the state-of-the-art etch-and-rinse dentin adhesives. Our goal is to show how alterations in the chemistry of methacrylate-based adhesives will lead to predictable changes in material properties (gp340/S. mutans attachment, reaction to lactic acid, mechanical properties) and to optimize features for in situ adhesive/dentin bond formation based on kinetics, fatigue and modeling of interfacial damage.
The specific aims are: 1) to synthesize the most promising methacrylate-based adhesives which minimize gp340/S. mutans attachment and neutralize the acidic micro-environment using an iterative combinatorial optimization/synthesis approach;2) to determine the effect of biologic fouling on degradation of the new dentin adhesives by studying the interaction between the degraded adhesive, gp340 and S. mutans;3) to test the mechanical and physicochemical properties of the gp340/S. mutans resistant adhesive at the interface with caries-free and caries-affected dentin.

Public Health Relevance

In 2005, 166 million restorations were placed in the U.S. and clinical studies indicate that more than half were replacement for failed restorations. Composite restorations may require replacement at 5.7 years failure of these restorations has been traced to the adhesive/dentin bond and attachment of the cariogenic bacterium, Streptococcus mutans, at the margin. The proposed project will result in the following patient benefits: 1) a substantial reduction in unreacted components that could be released from the adhesive;2) a substantial decrease in the material features that promote attachment of S. mutans;and 3) adhesives that neutralize the area to prevent acid-induced damage (cavitation) to the adjacent tooth structure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE022054-04
Application #
8668768
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Drummond, James
Project Start
2011-07-01
Project End
2016-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Kansas Lawrence
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Song, Linyong; Ye, Qiang; Ge, Xueping et al. (2018) Fabrication of hybrid crosslinked network with buffering capabilities and autonomous strengthening characteristics for dental adhesives. Acta Biomater 67:111-121
Parthasarathy, Ranganathan; Misra, Anil; Song, Linyong et al. (2018) Structure-property relationships for wet dentin adhesive polymers. Biointerphases 13:061004
Song, Linyong; Ge, Xueping; Ye, Qiang et al. (2018) Modulating pH through lysine integrated dental adhesives. Dent Mater :
Abedin, Farhana; Roughton, Brock; Ye, Qiang et al. (2017) Computer-aided Molecular Design of Water Compatible Visible Light Photosensitizers for Dental Adhesive. Chem Eng Sci 159:131-139
Ye, Qiang; Spencer, Paulette; Yuca, Esra et al. (2017) Engineered Peptide Repairs Defective Adhesive-Dentin Interface. Macromol Mater Eng 302:
Song, Linyong; Ye, Qiang; Ge, Xueping et al. (2017) Probing the neutralization behavior of zwitterionic monomer-containing dental adhesive. Dent Mater 33:564-574
Song, Linyong; Ye, Qiang; Ge, Xueping et al. (2016) Self-Strengthening Hybrid Dental Adhesive via Visible-light Irradiation Triple Polymerization. RSC Adv 6:52434-52447
McNiff, M L; Haynes, E P; Dixit, N et al. (2016) Thioredoxin fusion construct enables high-yield production of soluble, active matrix metalloproteinase-8 (MMP-8) in Escherichia coli. Protein Expr Purif 122:64-71
Song, Linyong; Ye, Qiang; Ge, Xueping et al. (2016) Tris(trimethylsilyl)silane as a co-initiator for dental adhesive: Photo-polymerization kinetics and dynamic mechanical property. Dent Mater 32:102-13
Song, Linyong; Ye, Qiang; Ge, Xueping et al. (2016) Development of methacrylate/silorane hybrid monomer system: Relationship between photopolymerization behavior and dynamic mechanical properties. J Biomed Mater Res B Appl Biomater 104:841-52

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