Utilizing hydrogen peroxide to promote angiogenesis in bone regeneration
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Non-union bone fractures occur when the bone does not properly heal after employing internal and external fixation and instead requires additional, more complicated medical interventions to achieve proper tissue repair. These injuries are particularly debilitating for patients, due to long recovery times, invasiveness, and complications associated with current treatment methods leveraging autografts and allografts. Newer therapies rely on scaffold-based systems loaded with expensive growth factors such as Bone Morphogenetic Protein 2 (BMP-2) and Vascular Endothelial Growth Factor (VEGF). As an alternative to these costly bioactive proteins, simple signaling molecules (SSMs) are an exciting tool being studied for their role in cellular signaling, as they are readily accessible, inexpensive, processible, and controllable. In particular, hydrogen peroxide (H2O2) is an attractive SSM which I have evaluated in this research as an alternative to VEGF. To examine its angioinductive effects, mesenchymal stem cells (MSCs) were exposed to varying concentrations of H2O2 and evaluated for certain factors indicative of cell viability and endothelial differentiation. Specifically, viability was studied based on cell count and adenosine triphosphate (ATP) production over a 7-day period. MSC endothelial differentiation was evaluated by measuring the endothelial markers von Willebrand Factor (vWF) and angiopoietin-1 (ang-1) using confocal microscopy and an enzyme linked immunosorbent assay (ELISA), respectively. The combined results of these experiments confirmed that H2O2 is indeed angioinductive promoting endothelial differentiation in vitro. A therapeutic window of 5 - 150 µM was determined with doses below this being sub-therapeutic and ones above this being cytotoxic. These initial promising results will help guide future research in which a sustained release method of H2O2 will be developed for future vascularized bone regenerative engineering applications such as in the repair of non-union fractures.
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M.S.