Date of Completion

9-1-2017

Embargo Period

8-24-2019

Advisors

Drs. Liisa Kuhn, Martin Freilich, Takanori Sobue, Anna Dongari

Field of Study

Dental Science

Degree

Master of Dental Science

Open Access

Campus Access

Abstract

Insufficient amount of alveolar bone is a common problem in implant dentistry that limits the treatment options available to restore lost dentition. Developing the technology that allows regenerating lost bone in a predictable fashion would open the door to limitless possibilities with respect to implant restorations. The overall goal of our studies was to determine whether the localized delivery of simvastatin from a collagen/hydroxyapatite scaffold would reduce inflammation and promote bone formation in calvarial and subcutaneous sites in mice. To approach this goal, simvastatin (5 and 25 μg) was delivered either from hydroxyapatite scaffold surgically positioned inside the unilateral calvarial defect or from the same scaffold located inside e-PTFE combi-cassette and surgically placed subcutaneously. We showed that simvastatin groups did not demonstrate signs of osteogenesis in neither calvarial nor subcutaneous sites and failed to show an effect on IL-6 and IL-10 expression. On the contrary, in the positive control group bone formation was promoted by 0.25 μg of BMP-2 in the calvarial defect model, but not in the subcutaneous site. Taken together, these preliminary data suggest that active form of simvastatin used in the dose of 5 and 25 μg delivered locally failed to induce bone formation and did not show effects on IL-6 and IL-10 expression in mouse calvarial critical-size defect model, as well as subcutaneous combi-cassette implantation model. Optimization of the delivery system and the dose of the medication to be delivered are critical aspects of successful therapy and may have been the factors influencing our results. In addition, our study showed that combicassette is not a replacement for calvarial defect bone testing of osteoinductive molecules and their role in osteogenesis. Collagen reporter mice are invaluable to distinguish bone formation from mineral precipitation on calcium phosphate based scaffolds. Simvastatin is not highly osteoinductive as compared to BMP-2. Simvastatin may need to be delivered at a later stage in bone healing rather than immediately at the time of surgery in order to optimize the immune responses that may assist with bone formation.

Major Advisor

Dr. Liisa Kuhn

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