A modular in vitro flow model to analyse blood-surface interactions under physiological conditions

Abstract

Newly developed materials for blood-contacting devices need to undergo hemocompatibility testing to prove compliance with clinical requirements. However, many current in vitro models disregard the influence of flow conditions and blood exchange as it occurs in vivo. Here, we present a flow model which allows testing of blood-surface interactions under more physiological conditions. This modular platform consists of a triple-pump-chip and a microchannel-chip with a customizable surface. Flow conditions can be adjusted individually within the physiological range. A performance test with whole blood confirmed the hemocompatibility of our modular platform. Hemolysis was negligible, inflammation and hemostasis parameters were comparable to those detected in a previously established quasi-static whole blood screening chamber. The steady supply of fresh blood avoids secondary effects by nonphysiological accumulation of activation products. Experiments with three subsequently tested biomaterials showed results similar to literature and our own experience. The reported results suggest that our developed flow model allows the evaluation of blood-contacting materials under physiological flow conditions. By adjusting the occurring wall shear stress, the model can be adapted for selected test conditions.

A Vascular Graft On‐a‐Chip Platform for Assessing the Thrombogenicity of Vascular Prosthesis and Coatings with Tuneable Flow and Surface Conditions

“…Current methods of in vitro thrombogenicity testing involve the use of static, agitating, and or shear-flow systems. [60,61] Miniaturized parallel plate and microfluidic flow platforms have also been described, [62,63] but fail to incorporate physiologicallike testing with blood flow, vascular prosthesis, coatings, and endothelial cells in a singular device. These platforms moreover overlook the control and versatility of microscale perfusion as an advantage for the testing and translation of novel prosthesis and or coatings in vitro.…”

A New In Vitro Blood Flow Model for the Realistic Evaluation of Antimicrobial Surfaces

“…A microfluidic single‐pass pumping setup was selected for the incubation, [ 36 ] where whole blood was pumped from a rotating reservoir through the microchannel with the test‐surface. Compared with steady pool systems, this setup avoids the accumulation of activation products as well as the exhaustion of source factors.…”

“…The setup is described in detail elsewhere. [ 36 ] Briefly, each pump channel consisted of an inlet valve, a pump chamber, and an outlet valve, periodically opened and closed by pneumatic membrane deflection. This setup leads to controlled filling and displacement with blood, causing a directed pulsatile volume flow.…”

“…Freshly drawn whole blood was pumped in a pulsatile flow with a maximum WSS of 17 dyn cm −2 over the microchannel chip. [ 36a ]…”

“…The WSS in the microchannel chip were previously quantified using microparticle‐imaging velocimetry. [ 36a ] The damping volumes applied in this study correspond to maximum shear stresses of 17 dyn cm − 2 (15 mL damping volume) and 7 dyn cm − 2 (50 mL damping volume), respectively. Both flow settings were chosen because similar values also occur in selected vascular devices.…”