Grants We Funded

Abstract
The goal of this proposal is to study how localized mechanical forces stimulate wound healing with special focus on the cell mediators of local wound angiogenesis. The project will have two focuses each taking approximately six months to accomplish. Since transient hypoxia stimulates angiogenesis, which is necessary for tissue regeneration, the currently used continuous tissue stretching by the Vacuum Assisted Closure (VAC) system may not be the optimal mechanical force to induce wound healing. The first six months will focus on using a servo-controlled stepping motor to alter the waveform, amplitude and frequency of mechanical force applied to a mouse model wound and monitor through immunohistochemistry and biochemical methods which variation of mechanic force leads to more robust angiogenesis. After determining the ideal mechanical force to apply to the mouse wound, the second six months will apply this mechanical force on eNOS and VEGF isoform-specific knockout mice and evaluate whether the absence of eNOS or the angiogenic isoform of VEGF will affect angiogenesis induced by stretch when compared to wild-type mice. This will determine whether VEGF and hypoxia induced eNOS are critical in stretch-induced angiogenesis. Through these simple experiments, we hope to clarify both the impact of continued versus waveform mechanical force on a wound and how mechanical forces interact with the angiogenesis pathway critical to sustain wound healing in order to further improve the VAC system for wound healing.