Introduction: As cardiovascular disease becomes more prevalent in aging society and continues to be one of the leading causes of death globally, early intervention is required to prevent disease onset and progression. Intervention can be accomplished by characterizing disease physiology, mechanism, and biomarkers to screen and develop efficient personalized therapies. Recent technological advances such as the development of 3-dimensional engineered heart tissue models and optical mapping can allow for the study of certain diseases for drug screening. However, the model can be prone to batch-to-batch variation, immature contractile force and inconsistent electrophysiology compared to the adult heart. Objective: The aim of this proposed study is to develop a low-cost open-source 3D bioprinter to fabricate reproducible and physiologically accurate heart tissues. Method: A desktop 3D printer was converted into a bioprinter by replacing the thermal extrusion nozzle with custom syringe pumps. The print fidelity was characterized using alginate ink and gelatin support bath. Functional tissues were printed using induced pluripotent stem cells differentiated cardiomyocytes (iPSC-CM) embedded in bioink containing sacrificial alginate and fibrinogen. Contractile output, electrophysiology, and sarcomere alignment of printed tissues was compared with manually casted tissues. Results: The custom 3D bioprinter showed high accuracy and precision of ±40um and ±4um for all axes. Printed filaments exhibited high uniformity across different printing parameters, while the diameter was primarily affected by the flowrate modifier and nozzle size, linearly. Cell-laden prints preserved high cell viability of >90% for over 2 weeks. Cell-laden printed tissues were compacted by dissolving alginate with EDTA induced spontaneous contraction and produced lower variation in normalized contractile force compared to manually casted tissues. Although printed tissues were found to have a longer APD80 under varying cycle length than manually casted tissues, both printed and manually casted tissues were shown to have similar action potential triangulation as ventricular cells with an APD30/APD80 of 0.70. Lastly, although printed tissues had a lower sarcomere alignment, exploratory findings suggested that printed tissues may influence intercellular structures. Overall, we have shown that our bioprinter is feasible in fabricating high-throughput and reproducible cardiac tissues for future drug and disease screening.
Ardin Sacayanan (Fri,) studied this question.