In 2006, 173 million composite and amalgam restorations were placed in the U.S. and clinical data suggest that >100 million were replacements. Since composites fail at a rate double that of amalgam, the emphasis on replacement therapy will increase with the elimination of amalgam. Recurrent decay is the primary reason for failure and 80-90% of recurrent decay is located at the gingival margin of the composite restoration. At this margin, the adhesive and its bond with dentin is the barrier between the restored tooth and the oral environment. In vivo degradation of the adhesive bond follows a cascade of events; these events are provoked by matrix metalloproteinases (MMPs) that degrade water-rich collagen that is not shielded by mineral or resin; acids and esterases released by the residual bacteria that contaminate the cavity; esterases and oral fluids that degrade the adhesive. Establishing and maintaining the interfacial integrity of the adhesive/dentin (a/d) bond has been a critical roadblock to durable composite restorations. Our approach involves a threefold strategy that: (i) exploits peptide engineering to disinfect the cavity and remineralize deficient dentin - the peptides are localized at the substrate by anchoring to the adhesive and dentin; (ii) engineers resins to resist chemical and enzymatic hydrolysis; and (iii) employs iterative feedback between synthesis, characterization and modeling to predict properties and promote targeted optimization of the adhesive. Combining bio- enabled techniques with synthesis of novel polymers, the overall hypothesis is that an adhesive formulation that achieves a durable, integrated a/d interfacial bond will provide an enhanced barrier to cariogenesis as compared to state-of-the-art dentin adhesives. Our goal is to show how altering the material chemistry and anchoring targeted peptides will lead to predictable changes in properties (resist chemical and enzymatic hydrolysis, disinfect the cavity, remineralize the dentin) and to optimize features for in situ a/d bond formation and interfacial integrity based on kinetics, fatigue, multi-scale structure/property characterization and predictiv modeling.
The specific Aims are: 1) to synthesize the most promising formulation that provides disinfection and remineralization using peptide engineering and iterative experimental/computational approaches; 2) to determine the hydrolytic and enzymatic resistance of the versatile resin matrices; 3) to test the bio-physicochemical and mechanical properties of the new adhesive at the interface between composite and caries-free and caries-affected dentin.

Public Health Relevance

In 2006, 173 million composite and amalgam restorations were placed in the U.S. and clinical studies suggest that more than half were replacements for failed restorations. Composite restorations may require replacement at 5.7 years-failure of these restorations has been traced to in vivo biodegradation of the composite restoration's adhesive bond layer. 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 bacteria that infect the prepared tooth; and 3) an adhesive bond layer that resists the mechanical and chemical stresses leading to in vivo biodegradation and composite restoration failure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE025476-01
Application #
8976655
Study Section
Special Emphasis Panel (ZRG1-MOSS-U (02))
Program Officer
Drummond, James
Project Start
2015-08-07
Project End
2020-01-31
Budget Start
2015-08-07
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
$358,912
Indirect Cost
$108,912
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
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 :
Wu, Xiaowen; Mahalingam, Suntharavathanan; VanOosten, Sarah Kay et al. (2017) New Generation of Tunable Bioactive Shape Memory Mats Integrated with Genetically Engineered Proteins. Macromol Biosci 17:
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
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
Yazici, Hilal; O'Neill, Mary B; Kacar, Turgay et al. (2016) Engineered Chimeric Peptides as Antimicrobial Surface Coating Agents toward Infection-Free Implants. ACS Appl Mater Interfaces 8:5070-81
Abedin, Farhana; Ye, Qiang; Song, Linyong et al. (2016) Effect of Partition of Photo-initiator Components and Addition of Iodonium Salt on the Photopolymerization of Phase-Separated Dental Adhesive. JOM (1989) 68:1090-1099

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