Cell-laden bioink circulation-assisted inkjet-based bioprinting to mitigate cell sedimentation and aggregation

Abstract

3D bioprinting precisely deposits picolitre bioink to fabricate functional tissues and organs in a layer-by-layer manner. The bioink used for 3D bioprinting incorporates living cells. During printing, cells suspended in the bioink sediment to form cell aggregates through cell-cell interaction. The formation of cell aggregates due to cell sedimentation have been widely recognized as a significant challenge to affect the printing reliability and quality. This study has incorporated the active circulation into the bioink reservoir to mitigate cell sedimentation and aggregation. Force and velocity analysis were performed, and a circulation model has been proposed based on iteration algorithm with the time step for each divided region. It has been found that (1) the comparison of the cell sedimentation and aggregation with and without the active bioink circulation has demonstrated high effectiveness of active circulation to mitigate cell sedimentation and aggregation for the bioink with both a low cell concentration of 1 × 106 cells/ml and a high cell concentration of 5 × 106 cells/ml; and (2) the effect of circulation flow rate on cell sedimentation and aggregation has been investigated, showing that large flow rate results in slow increments in effectiveness. Besides, the predicted mitigation effectiveness percentages on cell sedimentation by the circulation model generally agrees well with the experimental results. In addition, the cell viability assessment at the recommended maximum flow rate of 0.5 ml/min has demonstrated negligible cell damage due to the circulation. The proposed active circulation approach is an effective and efficient approach with superior performance in mitigating cell sedimentation and aggregation, and the resulting knowledge is easily applicable to other 3D bioprinting techniques significantly improving printing reliability and quality in 3D bioprinting.

Photo-/thermo-responsive bioink for improved printability in extrusion-based bioprinting

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3D Bioprinting in Microgravity: Opportunities, Challenges, and Possible Applications in Space

“…An attempt to cope with this issue was proposed by constantly agitating the reservoir, perpetually resuspending cells. [ 60 ] Here, microgravity will be an asset since the dispersion of the cell population will remain homogenous, even in a large volume of low viscosity liquid. Consequently, high cell density might be compatible with inkjet printing in space. Static Yield Stress—The static yield stress of a low‐viscosity material is also intrinsically low.…”

Bioinks adapted for in situ bioprinting scenarios of defect sites: a review

“…[27][28][29] In addition, attention needs to be paid to the interaction of bioinks with key cells, including cell settlement in the cartridge, cell viability during extrusion, and cell viability aer ink curing. [30][31][32]…”