Pulsatile pressure actuation enhances solute clearance in engineered vasculature through strain accumulation–release

Abstract Tissue homeostasis depends critically on the exchange of interstitial fluid between blood and tissues, as well as lymphatic drainage. While mechanical forces, such as external compression during physical activity, are known to accelerate interstitial fluid clearance, arterial pulsatility is hypothesized to play a similar role, especially in regions lacking lymphatic vasculature, such as the central nervous system. Here, we investigate how vascular pulsations modulate solute transport using a novel multi-microvessel pulsatile interstitial flow (PIF) chip. This platform enables real-time visualization of deformation and solute dynamics within a tissue-mimetic collagen hydrogel. Our results reveal a clipped Gent-like porohyperelastic response in acellular lumens, which is further amplified in vascularized lumens exhibiting asymmetric expansion-retraction behavior. Notably, microvessels induce strain retention within the hydrogel bulk, which is abruptly released during each pressure cycle. This cyclic strain retention and release mechanism coincides with a 1.3-fold increase in solute velocity, accelerating tracer clearance under pulsatile actuation compared to constant pressure. These findings highlight a vasculature-driven transport mechanism, where deformation-induced flow enhances interstitial clearance. These results provide new insights into how vascular dynamics may contribute to tissue homeostasis and interstitial fluid clearance.