Cell-laden bioink circulation-assisted inkjet-based bioprinting to mitigate cell sedimentation and aggregation
Cell-laden bioink circulation-assisted inkjet-based bioprinting to mitigate cell sedimentation and aggregation
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DOI：
10.1088/1758-5090/ac8fb7
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发表时间：
2022-09
期刊：
影响因子：
9
通讯作者：
Jiachen Liu;M. Shahriar;Heqi Xu;Changxue Xu
中科院分区：
文献类型：
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作者：
Jiachen Liu;M. Shahriar;Heqi Xu;Changxue Xu
三维(3D)生物打印精确地沉积皮利特生物墨水，以逐层方式制造功能组织和器官。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与细胞的相互作用沉淀形成细胞聚集体。由于细胞沉积而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一个重大挑战。这项研究将活跃的循环融入到生物墨水储存库中，以减轻细胞的沉积和聚集。对力和速度进行了分析，提出了基于迭代算法的环流模型，并对每个分区进行了时间步长计算。结果表明：(A)对于细胞浓度为1×10~6细胞/ml−-1和细胞浓度为5×10~6/ml/−/L的生物墨水，在有无活性生物墨水循环的情况下，细胞的沉降和聚集得到了有效的缓解；(B)研究了循环流量对细胞沉积和聚集的影响，结果表明，大流量会导致效率的缓慢增加。此外，环流模型预测的细胞沉积减缓效果百分比与实验结果基本吻合。此外，在建议的最大流速0.5mlmin−1下进行的细胞活性评估表明，循环对细胞的损害可以忽略不计。所提出的主动循环方法是一种有效和高效的方法，在缓解细胞沉积和聚集方面具有优越的性能，所获得的知识很容易应用于其他3D生物打印技术，从而显著提高3D生物打印的打印可靠性和质量。
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 × 106 cells ml−1 and a high cell concentration of 5 × 106 cells ml−1; 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 min−1 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.