Optical Resolution Photoacoustic Microscopy Reveals VEGF-induced Angiogenesis During Bone Regeneration

Angiogenesis is essential for bone homeostasis and repair. Newly formed vessels convey osteogenic progenitors during bone regeneration. However, the lack of continuous and label-free visualization of the bone microvasculature has resulted in little understanding of the neovascular dynamics. Here, we take advantage of optical-resolution photoacoustic microscopy (ORPAM) for label-free, intravital, long-term observation of the bone vascular dynamics. We quantify the angiogenic effect of locally-applied vascular endothelial growth factor (VEGF) in the mouse tibia defect model. VEGF treatment increased the concentration of total hemoglobin, vascular branching, and vascular density, which increased bone formation within the defect. These data demonstrated ORPAM as a useful imaging tool understand bone angiogenesis, and revealed the effectiveness of locally delivered therapeutic agents with sufficient sensitivity, contributing to the studying the bone regeneration in the future.