Out of 290 million dental restorations placed/year in the U.S., 200 million are replacements for failed restorations. This emphasis on replacement therapy is expected to grow as the public's concern regarding mercury and dental amalgam forces dentists to select alternative materials, e.g. composite. Moderate to large composite restorations have higher failure rates, more recurrent caries and increased frequency of replacement. The reduced clinical lifetime of moderate to large class II composite restorations can be particularly detrimental for our patients because removal of these restorations can lead to extensive loss of sound tooth structure with the concomitant need for enlarged, more complex restorations and eventually total tooth loss. Under in vivo conditions the adhesive/dentin (a/d) bond can be the first defense against substances that penetrate and undermine the composite restoration. Our recent in situ characterization of the molecular structure and micro-mechanics of the a/d interface indicated a serious limitation, i.e. physical separation of adhesive upon mixing with water in the demineralized dentin. The critical dimethacrylate (BisGMA), the component contributing the most to the crosslinked adhesive, infiltrated a fraction of the wet, demineralized dentin. In this revised competitive renewal application, we propose to build upon our results to develop a water- compatible adhesive by addressing the next chemical """"""""Achilles heel"""""""" of the a/d bond, i.e. ester linkages in the methacrylate matrix. The overall hypothesis is that in the presence of moist clinically relevant dentin substrates, methacrylate-based adhesives formulated to be water-compatible and esterase-resistant will provide enhanced interfacial structural integrity and increased durability. Our goal is to elucidate how alterations in the chemistry will lead, under clinically relevant conditions, to predictable changes in dentin adhesive material properties (structure, interfacial behavior, mechanical properties and durability) and to optimize features for in situ a/d bond formation based on kinetics, biocompatibility and modeling of interfacial damage.
The specific aims are: 1) to design and synthesize the most promising esterase-resistant, water- compatible methacrylate-based adhesives using an iterative combinatorial optimization/synthesis approach;2) to evaluate and test the physicochemical, mechanical and structural properties of the esterase-resistant, water- compatible methacrylate-based adhesives at the interface with such clinically relevant substrates as caries-free and -affected dentin;3) to evaluate the bond strengths between dentin and esterase-resistant, water- compatible methacrylate-based adhesives so that specific and quantifiable relationships between molecular structure and dentin bonding can be established. Project narrative Out of 290 million dental restorations placed annually in the United States, 200 million are replacements for failed restorations 1 and this emphasis on replacement therapy is expected to grow as the public's concern about mercury release from dental amalgam forces dentists to select alternative materials, e.g. composite resin. Under in vivo conditions the adhesive/dentin bond can be the first defense against substances that penetrate and undermine the composite restoration. If we are successful at completing the goals outlined in this project the direct benefits to the patient will be: 1) a substantial reduction in those components of the adhesive system that degrade releasing unreacted components and 2) development of adhesive systems that are compatible with the wet oral environment and thus, more resistant to premature degradation which undermines composite restorations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE014392-10
Application #
8058807
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Drummond, James
Project Start
2001-12-01
Project End
2013-04-30
Budget Start
2011-05-01
Budget End
2013-04-30
Support Year
10
Fiscal Year
2011
Total Cost
$329,018
Indirect Cost
Name
University of Kansas Lawrence
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
076248616
City
Lawrence
State
KS
Country
United States
Zip Code
66045
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
Tucker, Jenifer K; McNiff, Michaela L; Ulapane, Sasanka B et al. (2016) Mechanistic investigations of matrix metalloproteinase-8 inhibition by metal abstraction peptide. Biointerphases 11:021006
Abedin, F; Ye, Q; Parthasarathy, R et al. (2015) Polymerization behavior of hydrophilic-rich phase of dentin adhesive. J Dent Res 94:500-7
Singh, Viraj; Misra, Anil; Parthasarathy, Ranganathan et al. (2015) Viscoelastic properties of collagen-adhesive composites under water-saturated and dry conditions. J Biomed Mater Res A 103:646-57
Dixit, Namrata; Settle, Jenifer K; Ye, Qiang et al. (2015) Grafting MAP peptide to dental polymer inhibits MMP-8 activity. J Biomed Mater Res B Appl Biomater 103:324-31
Misra, Anil; Parthasarathy, Ranganathan; Singh, Viraj et al. (2015) Micro-poromechanics model of fluid-saturated chemically active fibrous media. Z Angew Math Mech 95:215-234
Misra, A; Parthasarathy, R; Ye, Q et al. (2014) Swelling equilibrium of dentin adhesive polymers formed on the water-adhesive phase boundary: experiments and micromechanical model. Acta Biomater 10:330-42
Spencer, P; Ye, Q; Misra, A et al. (2014) Proteins, pathogens, and failure at the composite-tooth interface. J Dent Res 93:1243-9
Song, Linyong; Ye, Qiang; Ge, Xueping et al. (2014) Synthesis and evaluation of novel dental monomer with branched carboxyl acid group. J Biomed Mater Res B Appl Biomater 102:1473-84
Laurence, Jennifer S; Nelson, Benjamin N; Ye, Qiang et al. (2014) Characterization of Acid-neutralizing Basic Monomers in Co-solvent Systems by NMR. Int J Polym Mater 63:361-367

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