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

Abstract: 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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: npj regenerative medicine. - 8, 1 (2023) , 15, ISSN: 2057-3995

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2023
• Creator: Grosso, Andrea ; Lunger, Alexander ; Burger, Maximilian G. ; Briquez, Priscilla S. ; Mai, Francesca ; Hubbell, Jeffrey A. ; Schaefer, Dirk J. ; Banfi, Andrea ; Di Maggio, Nunzia

Further information

• DOI: 10.1038/s41536-023-00288-1
• URN: urn:nbn:de:bsz:25-freidok-2349292
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:54 PM CET