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

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 o...

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Bibliographic Details
Published in:npj Regenerative medicine Vol. 8; no. 1; p. 15
Main Authors: Grosso, Andrea, Lunger, Alexander, Burger, Maximilian G., Briquez, Priscilla S., Mai, Francesca, Hubbell, Jeffrey A., Schaefer, Dirk J., Banfi, Andrea, Di Maggio, Nunzia
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 13.03.2023
Nature Publishing Group
Nature Portfolio
Subjects:
631/532/2074
631/61/490
Angiogenesis
Biomaterials
Biomedical and Life Sciences
Biomedicine
Blood vessels
Bones
Cell Biology
Drug dosages
Immunology
Physiology
Regenerative medicine
Regenerative Medicine/Tissue Engineering
Stem Cells
Surgery
Tissue engineering
Vascular endothelial growth factor
ISSN:2057-3995, 2057-3995
Online Access:Get full text
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Summary: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.
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ISSN:2057-3995
2057-3995
DOI:10.1038/s41536-023-00288-1