Hence, blood trauma might be reduced with this design. Based on these encouraging results, future in vitro investigations to investigate actual blood damage are intended.

Anatomic pathologies such as stenosed or regurgitating heart valves and artificial organs such as heart assist devices or heart valve prostheses are associated with non-physiological flow. This regime is associated with regions of spatially high-velocity gradients, high-velocity and/or pressure fluctuations as well as neighbouring regions with stagnant flow associated with high residence time. These hemodynamic conditions cause destruction and/or activation of blood components and their accumulation in regions with high residence time. The development of next-generation artificial organs, which allow long-term patient care by reducing adverse events and improve quality of life, requires the development of blood damage models serving as a cost function for device optimization. We summarized the studies underlining the key findings with subsequent elaboration of the requirements for blood damage models as well as a decision tree based on the classification of existing blood damage models. The four major classes are Lagrangian or Eulerian approaches with stress- or strain-based blood damage. Key challenges were identified and future steps towards the translation of blood damage models into the device development pipeline were formulated. The integration of blood damage caused by turbulence into models as well as in vitro and in vivo validation of models remain the major challenges for future developments. Both require the development of novel experimental setups to provide reliable and well-documented experimental data.

Left ventricular assist devices (LVADs) have become a standard therapy for patients with severe heart failure. As low blood trauma in LVADs is important for a good clinical outcome, the assessment of the fluid loads inside the pump is critical. More specifically, the flow features on the surfaces where the interaction between blood and artificial material happens is of great importance. Therefore, experimental data for the near-wall flows in an axial rotary blood pump were collected and directly compared to computational fluid dynamic results. For this, the flow fields based on unsteady Reynolds-averaged Navier-Stokes simulations-computational fluid dynamics (URANS-CFD) of an axial rotary blood pump were calculated and compared with experimental flow data at one typical state of operation in an enlarged model of the pump. The focus was set on the assessment of wall shear stresses (WSS) at the housing wall and rotor gap region by means of the wall-particle image velocimetry technique, and the visualization of near-wall flow structures on the inner pump surfaces by a paint erosion method. Additionally, maximum WSS and tip leakage volume flows were measured for 13 different states of operation. Good agreement between CFD and experimental data was found, which includes the location, magnitude, and direction of the maximum and minimum WSS and the presence of recirculation zones on the pump stators. The maximum WSS increased linearly with pressure head. They occurred at the upstream third of the impeller blades and exceeded the critical values with respect to hemolysis. Regions of very high shear stresses and recirculation zones could be identified and were in good agreement with simulations. URANS-CFD, which is often used for pump performance and blood damage prediction, seems to be, therefore, a valid tool for the assessment of flow fields in axial rotary blood pumps. The magnitude of maximum WSS could be confirmed and were in the order of several hundred Pascal.

Introduction: Continuous-flow left ventricular assist devices have evolved from short-time therapy into permanent or so-called destination therapy. One complication in long-term usage is bleeding, which is presumably attributed to shear-induced interference of left ventricular assist devices with the coagulation system. Methods: The influence of dynamic shear stresses on primary hemostasis by single or multiple passes through left ventricular assist devices was investigated. A novel Couette-type shearing device, especially fitted to simulate left ventricular assist devices with highly dynamic and repetitive stresses, was developed. To evaluate the clotting ability of the blood and thus the bleeding tendency, the closure time of the platelet function analyzer (PFA-100®, Dade Behring, Marburg, Germany) was used. The relationship of the PFA-100 closure time was fitted to measurement points with shear stress and exposure time as parameters. Results: 76 samples of human blood collected from four different healthy donors in sodium-citrate anticoagulant solution were tested, including 20 control samples. A damage model according to the power law approach could be developed. A linear correlation of shear stress and exposure time to the PFA-100 closure time could be determined. In addition, a model was developed to calculate the increase in the PFA closure time on the basis of shear stress over time curves. Discussion: With the shearing device, half-sine-wave-shaped shear stress patterns relevant to rotary blood pumps can be achieved with very good repeatability. The proposed damage model could be used to compare and optimize left ventricular assist devices under development. The tests showed a significant decrease in coagulability after only a few repetitions.

Three-dimensional tissue cultures are important models for the study of cell-cell and cell-matrix interactions, as well as, to investigate tissue repair and reconstruction pathways. Therefore, we designed a reproducible and easy to handle printable bioreactor system (Teburu), that is applicable for different approaches of pathway investigation and targeted tissue repair using human tissue slices as a three-dimensional cell culture model. Here, we definitively describe Teburu as a controlled environment to reseed a 500-µm thick decellularized human liver slice using human mesenchymal stroma cells. During a cultivation period of eight days, Teburu, as a semi-open and low consumption system, was capable to maintain steady pH and oxygenation levels. Its combination with additional modules delivers an applicability for a wide range of tissue engineering approaches under optimal culture conditions. K E Y W O R D S 3D cell culture, 3D-printing, bioreactor, optogenetics, recellularization 1036 | DANESHGAR Et Al. How to cite this article: Daneshgar A, Tang P, Remde C, et al. Teburu-Open source 3D printable bioreactor for tissue slices as dynamic three-dimensional cell culture models.