Development and Characterization of a Magnesium/Polymer Composite for Guided Bone RegenerationBrown, Andrew J. (2016) Development and Characterization of a Magnesium/Polymer Composite for Guided Bone Regeneration. Doctoral Dissertation, University of Pittsburgh. (Unpublished)
AbstractEvery year in the United States, 2 million implant supported dental prostheses are placed in order to restore the functionality and cosmetic appearance of missing teeth. In over half of these cases, a bone grafting procedure must be performed to build the bony foundation necessary for implant survival. Unfortunately, the current gold-standard bone graft substitutes impart limited osteoconductivity and exhibit long degradation times leading to unpredictable outcomes. Thus, there exists a significant need for degradable dental bone graft substitutes capable of enhancing the bone regeneration process. The overall goal of this work was to design guided bone regeneration devices that address the limitations of current bone graft substitutes and barrier membranes. First, bone graft substitutes were synthesized from metallic magnesium (Mg) particles and poly-(lactic-co-glycolic acid) (PLGA) and subsequently characterized. These Mg/PLGA scaffolds were found to release magnesium at a controllable rate that ameliorated the acidic degradation profile of PLGA and enhanced bone marrow stromal cell proliferation in vitro. Next, we evaluated the Mg/PLGA scaffolds in a canine socket preservation model and found that the scaffolds increased bone height and bone volume regenerated relative to controls. Other groups have demonstrated enhanced osteogenic activity surrounding magnesium implants in orthopedic applications. However, the cellular mechanisms underlying these observations have not been well defined. Our next objective was to assess these cellular mechanisms in vitro, following exposure of bone marrow stromal cells (BMSCs) to varying concentrations of magnesium ion, simulating device degradation. We found that certain magnesium concentrations enhanced cell proliferation and matrix mineralization and impacted gene pathways associated with increased osteogenic activity. Finally, we designed and evaluated a Mg/PLGA barrier membrane and magnesium micromesh in a canine vertical ridge augmentation model which showed promise for a fully degradable and osteoconductive magnesium-based guided bone regeneration therapy. This work established the use of degradable magnesium devices for enhancing dental bone regeneration while expanding knowledge of the cellular mechanisms impacted by magnesium’s degradation. Share
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