Moussa, Dina2020-02-262020-02-262018-12https://hdl.handle.net/11299/211784University of Minnesota Ph.D. dissertation. December 2018. Major: Oral Biology. Advisor: Conrado Aparicio. 1 computer file (PDF); xii, 207 pages + 1 supplementary .ZIP file.Dental caries, i.e., tooth decay mediated by bacterial activity, is the most widespread chronic disease worldwide. With the evolution of bonded esthetic restorations, that look and function like natural teeth, it has become almost impossible for clinicians to proceed without them to restore carious teeth. Nonetheless, durability of esthetic restorations is notably compromised because of recurrent caries (RC), the principle cause of failure for esthetic restorations. RC mainly results from either waterborne (hydrolytic, acidic, enzymatic) and/or bacteria-mediated degradation of hydrophilic adhesives, which are required to interact with hydrated dentin at tooth-restoration interfaces. Therefore, transforming the hydrophilic interface into a water repellent one and/or incorporating a potent antibiofilm agent are potential strategies to resist RC. We have developed a novel application of amphipathic anti-microbial peptides (AAMPs) on dentin simultaneously used as a 2-tier protective system, hydrophobicity modulators and antibiofilm agents to resist RC around restoration margins. Cationic short AAMPs have been recently identified as potential alternatives to traditional antimicrobial agents and antibiotics due to their ability to specifically target the complex and heterogeneous organization of microbial communities where the latter are unlikely to develop resistance. We tested a series of AAMPs with strong amphipathic properties to assess their structure-function relationships. We found that AAMPs secondary structure (high portion of b-sheet), antimicrobial potency, and ability of the peptides to form hydrophobic coatings on dentin were inter-related. We also determined that AAMPs had preferential adsorption on the mineral phase of dentin, which suggested that peptides arrange their cationic and hydrophilic motifs in direct contact with the negatively-charged minerals in the hydrophilic dentin. We sought to study the impact of these AAMPs coatings on the dental plaque microbial community composition as well as their bacterial selectivity. We found that all D-amino acid AAMPs induced a marked shift in the plaque community by targeting 3 primary acidogenic colonizers. The consequent substantial antibiofilm potency of AAMPs-coated dentin was visualized using advanced bioimaging throughout 1 mm-deep dentin-composite interfaces. In conclusion, hydrophobic antibiofilm dentin is a versatile new approach to fortify the otherwise vulnerable adhesive-based interfaces of bonded restorations against the highly prevalent devastating RC.enAmphipathic Antimicrobial PeptidesDental RestorationsDentinHydrophobic CoatingMultiphoton-second harmonic generation imagingRecurrent CariesThesis or Dissertation