Host and bacterial enzyme-mediated approaches to produce durable direct and indirect restorations

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Summary Dental caries continues to be a public health issue, especially more evident in underserved populations throughout the U.S. Unfortunately, especially with an ageing population, hundreds of thousands of resin composite restorations are replaced each year due to recurring decay and fracture. According to a number of cohort studies, the average life-span of this type of restoration is 10 years or less, depending on the caries risk level of the patient and on the complexity of the restorative procedure. This proposal represents an effort to develop novel antimicrobial structures, based on a targeted approach specifically against dysbiotic biofilm. Bacterial coalescence will be prevented by using GTF inhibitors, made polymerizable by functionalization with stable methacrylamides. In addition, MMP-inhibiting moieties will be added to a polymerizable monomer, improving the stability of the collagen in the hybrid layer. Ultimately, this will save millions of dollars annually and the unnecessary loss of additional tooth structure that comes with every re-treatment. The proposed approach will improve the longevity of restorations by: 1. Designing monomers containing known GTF-inhibiting moieties, thus making them available non-transiently at the surface of restorations. 2.Utilizing polymerizable functionalities that depart from the water/esterase-labile methacrylates. Methacrylamides are well known for their resistance to degradation by hydrolysis, and the systems proposed here will also be stable to enzymatic attack. 3. Incorporating MMP-inhibiting moieties on the methacrylamide monomer to the used as the adhesive, thus preserving the integrity of the collagen long-term. 4. Testing the materials in a physiologically relevant environment, mimicking the conditions in the mouth in terms of mechanical loading, bacterial challenge and presence of saliva.