Simulating physiological blood maintenance: A dialysis-integrated in vitro flow loop for realistic hemocompatibility evaluation of devices

Conventional blood flow-loop systems, employing animal or rarely fresh human blood, used in in vitro testing of blood-contact devices fail to simulate the actual physiological conditions. This study aims to develop a metabolically sustainable blood flow loop system to be used in cardiovascular device testing, by integrating nutrition, oxygenation, and dialysis modules. Two flow loop systems with human blood were compared: (1) control circuit with oxygenation and (2) experimental circuit with the addition of nutrition, oxygenation, and dialysis modules. Blood was circulated for 12 and 48 h, and hemolysis (NIH, pfHb, bilirubin, haptoglobin), blood gases (pH, glucose, lactate), inflammation (IL-8, TNF-α, C3a), coagulation (fibrinogen, TAT), platelet/endothelial activation (β-TG, vWF), and ferritin levels were measured over time. While pH decrease, lactate increase, and inflammatory/coagulation markers increased in the control group, these parameters were stable or decreased in the dialysis group. NIH was 77%–81% lower in dialysis, and vWF decreased 55%–73% in dialysis while increasing in control (p < 0.05). The improved flow loop system reduced hemolysis, inflammation, and coagulation by maintaining the metabolic balance and biochemical integrity of blood during long-term circulation. This approach has the potential to improve in vitro testing of blood-contacting medical devices.