Flow-Induced Vascular Remodeling On-Chip: Implications for Anti-VEGF Therapy

Abstract

Impaired vascular remodeling is linked to tumor progression, impacting the efficacy of anti-vascular therapies. However, the interplay between blood flow and vascular endothelial growth factor (VEGF) in driving vascular remodeling remains unclear. We optimized a human vasculature-on-chip system for long-term perfusion to quantify vascular remodeling under physiologically low and tumor-mimicking high VEGF conditions. Live imaging shows that at low VEGF levels, flow-conditioned vascular networks remodeled like animal models, en-hancing flow velocities. Conversely, static networks lacking flow exhibited continuous growth, loss of network hierarchy, and decreased flow velocities. At tumor-mimicking high VEGF levels, flow-conditioned vessels showed aberrant overgrowth, which was blocked by the anti-VEGF tumor drug bevacizumab, restoring flow-induced remodeling. Without flow, however, high VEGF slowed vessel growth compared to low VEGF, while anti-VEGF treatment restored continuous growth. These findings provide valuable insights into optimizing anti-angiogenic therapies by exploiting VEGF modulation and flow conditions for vascular remodeling and improved tumor treatment.