Objective <p>Assessing circulatory hemodynamics in-vitro is crucial for cardiovascular device design before in-vivo testing. Current mock circulation loops (MCLs) rely on simplified, lumped-parameter hydraulic representations of human circulation. There is a need for a more sophisticated MCL that can accurately represent the human circulatory physiology and allow for critical assessment of device-supported hemodynamics.</p> Methods <p>An anatomy-mimicking MCL design guided by one-dimensional flow models has been developed, using tree-like arterial casts to create a complex system. The MCL comprises cardiac simulators, systemic circulatory subsystems consisting of 46 connected arterial casts, and lumped venous and pulmonary components. A parameter tuning process was also developed to ensure that the simulated MCL baselines are consistent with targeted healthy or heart failure scenarios.</p> Results <p>Blood pressure and flow waveforms in the thoracic aorta, upper and lower limb arteries and abdominal organs (kidney, liver, spleen, etc.) were reproduced and validated against published data. Complex afferent and efferent flows in cerebral circulation and phasic coronary flow subjected to myocardial compression effect were replicated with precision. Pulse wave behavior was authentically generated and compared favorably to the published in-vivo and in-silico results.</p> Conclusion <p>This wave transport-preserving MCL is able to simulate pulsatile human circulatory hemodynamics with sufficient detail and accuracy. Complex cardiovascular device-intervened hemodynamics in large arteries and end organs can be systematically assessed using this new MCL, potentially contributing to a rapid and accurate in-vitro simulation to help advance device design and functional optimization.</p>