HYBERFLOW — enabling non-invasive flow rate feedback control in bioprinting via hydraulic actuation

Bioprinting offers transformative potential for tissue engineering by enabling the precise fabrication of complex tissue constructs. Of the different bioprinting techniques, extrusion-based bioprinting is the most common, often relying on pneumatic actuation to extrude bioinks. Changes in the viscosity of the bioink, e.g., due to inhomogeneities in the ink or temperature changes in the printing environment, affect the extrusion flow rate if the pneumatic pressure is not adapted accordingly. While maintaining a constant flow rate improves the printing results significantly, continuous monitoring of the flow rate in combination with feedback control is required. Current systems rely on a flow rate sensor to directly measure the flow rate of the bioink, which negatively affects the bioink and requires frequent re-calibrations. To overcome these issues, we are using a hydraulic actuation fluid and implementing a flow rate feedback control based on the flow rate of the actuation fluid rather than the bioink itself. We integrated this concept of hydraulic actuation into our novel hydraulic bioextruder with real-time flow rate control called ”HYBERFLOW”. In this paper, we briefly present the design and our experimental validation of the system. Our experiments are aimed to determine whether the flow rate of the actuation fluid corresponds to the flow rate of the extrusion material, investigate the capabilities of the HYBERFLOW to achieve and maintain a desired flow rate with highly heterogeneous bioinks and determine the limits of the HYBERFLOW in terms of bioink viscosity and printing nozzle geometry. We found that the deviation in volume of the extruded bioink compared to the measured volume of the actuation fluid is less than 4%. This clearly shows the feasibility of controlling the flow rate of the bioink by controlling the flow rate of the actuation fluid. As a result, the flow rate sensor only needs to be in contact with actuation fluid, which is less sensitive and does not require the sensor to be re-calibrated due to its more consistent fluid properties. Furthermore, when extruding a bioink consisting of layers with different viscosities, the feedback control was able to maintain the desired flow rate, leading to a more consistent geometry of the printing result. In conclusion, HYBERFLOW enables real-time flow rate-controlled bioextrusions for improved printing outcomes without negatively affecting the bioink.