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VEGF dose controls the coupling of angiogenesis and osteogenesis in engineered bone
VEGF dose controls the coupling of angiogenesis and osteogenesis in engineered bone
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VEGF dose controls the coupling of angiogenesis and osteogenesis in engineered bone
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VEGF dose controls the coupling of angiogenesis and osteogenesis in engineered bone
VEGF dose controls the coupling of angiogenesis and osteogenesis in engineered bone
Journal Article

VEGF dose controls the coupling of angiogenesis and osteogenesis in engineered bone

2023
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Overview
Vascular endothelial growth factor-A (VEGF) physiologically regulates both angiogenesis and osteogenesis, but its application in bone tissue engineering led to contradictory outcomes. A poorly understood aspect is how VEGF dose impacts the coordination between these two processes. Taking advantage of a unique and highly tunable platform, here we dissected the effects of VEGF dose over a 1,000-fold range in the context of tissue-engineered osteogenic grafts. We found that osteo-angiogenic coupling is exquisitely dependent on VEGF dose and that only a tightly defined dose range could stimulate both vascular invasion and osteogenic commitment of progenitors, with significant improvement in bone formation. Further, VEGF dose regulated Notch1 activation and the induction of a specific pro-osteogenic endothelial phenotype, independently of the promotion of vascular invasion. Therefore, in a therapeutic perspective, fine-tuning of VEGF dose in the signaling microenvironment is key to ensure physiological coupling of accelerated vascular invasion and improved bone formation.