VEGF dose controls the coupling of angiogenesis and osteogenesis in engineered bone
Andrea Grosso1, Alexander Lunger1,2, Maximilian G Burger1,2
1Regenerative Angiogenesis Laboratory, Department of Biomedicine, Basel University Hospital and University of Basel, Hebelstrasse 20, 4031, Basel, Switzerland.
NPJ Regenerative Medicine
|March 14, 2023
Summary
Optimizing vascular endothelial growth factor-A (VEGF) dosage is crucial for bone tissue engineering. A specific VEGF dose range enhances both blood vessel growth and bone formation, improving therapeutic outcomes.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Vascular Biology
Background:
- Vascular endothelial growth factor-A (VEGF) influences angiogenesis and osteogenesis.
- Contradictory outcomes exist regarding VEGF's application in bone tissue engineering.
- The impact of VEGF dosage on osteo-angiogenic coupling remains unclear.
Purpose of the Study:
- To investigate the dose-dependent effects of VEGF on osteo-angiogenic coupling in tissue-engineered bone grafts.
- To determine the optimal VEGF dose for coordinating vascular invasion and osteogenesis.
- To elucidate the mechanisms by which VEGF dose regulates these processes.
Main Methods:
- Utilized a highly tunable platform to test VEGF doses across a 1,000-fold range.
- Evaluated vascular invasion and osteogenic commitment of progenitor cells.
- Assessed Notch1 activation and endothelial cell phenotype.
Main Results:
- Osteo-angiogenic coupling is highly sensitive to VEGF dose.
- A narrow VEGF dose range significantly improved bone formation by stimulating vascular invasion and osteogenic commitment.
- VEGF dose modulated Notch1 activation and induced a pro-osteogenic endothelial phenotype, independent of vascular invasion.
Conclusions:
- Fine-tuning VEGF dose is critical for successful bone tissue engineering.
- Optimal VEGF signaling promotes physiological coupling of vascularization and bone formation.
- Targeted VEGF modulation offers therapeutic potential for enhanced bone regeneration.
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