Graduation Date

Summer 8-14-2015

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Richard A. Reinhardt

Abstract

Introduction: Simvastatin (SIM) is a hypolipidemic drug that has been shown to have anti-inflammatory and bone anabolic properties. The aim of this study was to examine the effects of novel locally-applied SIM conjugated with methoxypolyethylene glycol to form micelles (SIM/SIM-mPEG) in an experimental periodontitis model in rats using micro-computed tomography (µ-CT) and histologic evaluation.

Methods: Experimental periodontitis was induced using silk ligatures around the maxillary right second molar (M2) in 40 Sprague-Dawley rats. Rats were divided into five groups using SIM/SIM-mPEG at 0.5, 1.0, or 1.5 mg SIM doses, mPEG-alone or no drug (ligature-alone) injected into the palatal M1-M2 gingiva at baseline and 1- and 2-weeks post ligature-placement. Rats were euthanized three weeks after baseline and linear measurements were taken using µ-CT from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) between M1-M2. Using hematoxylin and eosin histology, cell counts and area of inflammation were recorded in the connective tissue (CT) of the papilla between M1-M2 interproximally. One-way ANOVA and Pearson correlations were calculated.

Results: All three doses of the micelle resulted in significantly less bone loss compared to the ligature-alone group (p ≤ 0.007). Significantly greater percentages of lymphocytes were found only in the ligature-alone and mPEG groups compared to contralateral controls (p ≤ 0.05). 1.0 and 1.5 mg SIM/SIM-mPEG groups showed significantly more uninflamed CT than all other treatment groups (p ≤ 0.05).

Conclusions: SIM/SIM-mPEG significantly decreased the amount of bone loss and inflamed tissue in experimental periodontitis near the injection site.

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