Department of Industrial, Manufacturing, and Systems Engineering, Texas Tech University, Lubbock, TX 79409, United States of America.
Biofabrication. 2022 Oct 3;14(4). doi: 10.1088/1758-5090/ac8fb7.
Three-dimensional (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 (a) 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 × 10cells mland a high cell concentration of 5 × 10cells ml; and (b) 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 minhas 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.
三维（3D）生物打印可以精确地沉积皮升级的生物墨水，以逐层方式构建功能性组织和器官。用于 3D 生物打印的生物墨水包含活细胞。在打印过程中，悬浮在生物墨水中的细胞通过细胞间相互作用沉淀形成细胞聚集体。由于细胞沉淀形成的细胞聚集体已被广泛认为是影响打印可靠性和质量的重大挑战。本研究将主动循环纳入生物墨水储液器中，以减轻细胞沉淀和聚集。进行了力和速度分析，并基于迭代算法提出了一种循环模型，该算法具有每个分区的时间步长。研究发现：(a) 有无主动生物墨水循环的细胞沉淀和聚集的比较表明，主动循环对于降低低细胞浓度（1×10 个细胞/ml）和高细胞浓度（5×10 个细胞/ml）的生物墨水中的细胞沉淀和聚集具有很高的有效性；(b) 循环流速对细胞沉淀和聚集的影响进行了研究，结果表明，大流速会导致有效性的缓慢增加。此外，循环模型对细胞沉淀的预测缓解效果百分比与实验结果基本一致。此外，在推荐的最大流速 0.5 ml/min 下对细胞活力的评估表明，由于循环，细胞几乎没有受到损伤。所提出的主动循环方法是一种有效且高效的方法，在减轻细胞沉淀和聚集方面具有卓越的性能，并且相关知识可以很容易地应用于其他 3D 生物打印技术，从而显著提高 3D 生物打印的可靠性和质量。
