Inclusion of a New Class of MMP-Inhibitor, Extracellular Matrix Protection Factor 2 (ECPF-2), Contributes to a Stronger, More Durable Composite Dental Restoration

Date of Award

2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Marina D’Angelo, PhD

Second Advisor

Fusun Ozer, DDS, PhD

Third Advisor

Ruth Borghaei, PhD

Fourth Advisor

Brian Balin, PhD

Abstract

Each year in the United States alone, the prevention and restorative treatment of tooth decay exceed costs of $100 billion. A considerable percentage of these costs arise from the need for retreatment and replacement of failed restorations. An innovative means of preventing the failure of dental restorations would ease the financial burden associated with retreatment procedures. In addition to bacterial enzymes which contribute to the degradation of the hybrid layer between the composite resin material and dentin, current research indicates a role for endogenous matrix metalloproteinases (MMPs), in degradation of this hybrid layer. It has been demonstrated that acid etching of the tooth in preparation for administration of the adhesive bonding agent will activate endogenous MMPs in the hybrid layer including Matrix Metalloproteinase-8 (MMP-8), a collagenase enzyme present in the hybrid layer. The contemporary clinical solution to hybrid-layer degradation is the use of a nonspecific protease inhibitor, chlorhexidine gluconate (2%), at the time of treatment. Since MMP-8 is primarily responsible for the degradation of the organic component of dentin, predominantly type I collagen fibers, a more specific targeted protease inhibition should increase bond strength in restorations. To address this notion, our laboratory has developed a proprietary compound, Extracellular Matrix Protection Factor-2 (ECPF-2), to specifically inhibit the interaction of MMP-8 and collagen type I. Utilizing a novel tooth-restoration model, we treated non-carious, extracted human third molars with ECPF-2 after acid etching and before application of the adhesive bonding agent. We tested two conformations of ECPF-2, a linear sequence (ECPF-2 Lin) and a cyclized sequence (ECPF-2 Cyc) of the peptide. Following placement and curing of the composite material, teeth were either immediately prepared for bond strength testing (IMM) or first exposed to a regimen of artificial, accelerated aging (TMA) prior to assaying and bond strength testing. A portion of the prepared samples were ground into a fine dentin powder and the extracted proteins were assayed to determine the levels of enzyme protein or activity. In addition, designated samples were cut with a milling tool into beams (dimensions of 1mm x 1mm) and subjected to microtensile bond strength testing with a single-speed actuator. Teeth treated with ECPF-2 exhibited statistically significant increased bond strength (5μg ECPF-2 Lin = 39.6 megapascals [MPa]) compared to chlorhexidine treated preparations (20.01 MPa) and bond strength was improved even after one-year accelerated aging (5μg ECPF-2 Lin = 26.8 MPa, versus chlorhexidine = 21.4 MPa) even though, as expected, the absolute values were reduced. The enhanced bond strength in ECPF-2-treated preparations indicates the importance of this novel inhibitor with respect to clinical and commercially-available applications in extending the lifespan of dental restorations.

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