Flow‐Induced Vascular Remodeling on‐Chip: Implications for Anti‐VEGF Therapy

Abstract Impaired vascular network 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 network remodeling remains unclear. This work optimizes a human vasculature‐on‐chip system for long‐term perfusion to quantify vascular network remodeling under physiologically low and tumor‐mimicking high VEGF conditions. Live imaging shows that at low VEGF levels, flow‐conditioned vascular networks remodel like animal models, enhancing flow velocities. Conversely, static networks lacking flow exhibit continuous growth, loss of network hierarchy, and decreased flow velocities. At tumor‐mimicking high VEGF levels, flow‐conditioned vessels show aberrant overgrowth, which is blocked by the anti‐VEGF tumor drug bevacizumab, restoring flow‐induced remodeling. Without flow, however, high VEGF slows vessel growth compared to low VEGF, while anti‐VEGF treatment restores 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.