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

Vascular remodeling is critical for tumor progression and significantly affects anti-vascular therapies. However, the interplay between blood flow and vascular endothelial growth factor (VEGF) in driving vascular remodeling remains poorly understood. We optimized a human vasculature-on-chip system for long-term perfusion at physiological VEGF levels to quantify vascular remodeling under low and tumor-mimicking high VEGF conditions. Live imaging shows that at physiologically low VEGF levels, flow-conditioned vascular networks remodeled similarly to animal models, resulting in increased flow velocities. In contrast, 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.