Simulated microgravity with physiological shear reveals endothelial disruption in a dual-stimulus bioreactor

Microgravity alters vascular homeostasis by disrupting mechanical cues critical to endothelial function. Here, we report a benchtop bioreactor that integrates simulated microgravity with physiological laminar shear stress ( ~ 3 dyn/cm²) to examine acute endothelial responses (16 h exposure). Using human umbilical vein endothelial cells (HUVECs), we observed cytoskeletal disorganization, loss of vascular endothelial cadherin junctions, and altered secretion of angiogenic factors, including Angiopoietin 2 (Angpt-2), Vascular Endothelial Growth Factor (VEGF), and Platelet-Derived Growth Factor (PDGF). This dual-stimulus platform bridges static microgravity and flow-driven endothelial models, enabling mechanistic studies of vascular dysfunction in spaceflight-relevant conditions and offering a framework for standardized microgravity-flow experimentation.