Modeling of cell distribution dynamics in cell-laden bioink with active circulation
Modeling of cell distribution dynamics in cell-laden bioink with active circulation
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DOI：
10.1016/j.addma.2023.103669
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发表时间：
2023-07
影响因子：
11
通讯作者：
Jiachen Liu;Heqi Xu;M. Shahriar;Changxue Xu
中科院分区：
文献类型：
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作者：
Jiachen Liu;Heqi Xu;M. Shahriar;Changxue Xu
三维生物打印被认为是构建生物功能组织和器官的未来，以满足组织再生和器官移植日益增长的需求。在沉积由生物材料和活细胞组成的生物墨水期间，细胞由于占主导地位的重力而沉积，导致在生物墨水储存器底部通过细胞-细胞相互作用的细胞聚集。它在液滴形成和打印后细胞分布方面显着破坏了打印性能，因此被认为是3D生物打印中的关键问题。先前的研究已经证明了循环生物墨水减轻沉降和相关细胞聚集的可行性，具有潜在的上级有效性。本研究的重点是建立沉降模型，预测细胞分布的生物墨水库的动态性能，考虑细胞聚集在固定的生物墨水和循环的生物墨水的影响。建立了基于时间域的迭代沉降模型，并采用Nelder-Mead单纯形算法对细胞聚集的影响进行了最小二乘优化。在基于喷墨的生物打印过程中，细胞聚集在载有细胞的生物墨水的沉降中的作用已经被理论和实验研究。研究发现：（1）考虑单细胞的沉降模型低估了静止流体中细胞浓度的实验定量，高估了循环生物墨水中的泵送能力，而考虑细胞聚集的沉降模型与这两种模型基本一致：（2）静止生物墨水中细胞聚集体的形成加速了细胞的沉降，这是由于细胞较大的尺寸导致较高的沉降速度;（3）所形成的细胞聚集降低了泵送能力和对循环生物墨水中细胞聚集的缓解效果。采用较高的初始细胞浓度（1 × 106 ~ 3 × 106 ~ 5 × 106个细胞/ml），较低的聚合物浓度（1%~ 0.5 ~ 0.25%（w/v）），并且从30分钟到60分钟到90分钟的更长的打印时间增加了形成细胞聚集体的机会，这是由于更大的沉降诱导的细胞积累和更短的距离诱导的更大的细胞聚集。细胞相互作用
Three dimensional bioprinting is recognized as the future of constructing bio-functional tissues and organs to satisfy the increasing demand of tissue regeneration and organ transplantation. During depositing the bioink consisting of biological materials and living cells, cells sediment due to dominant gravitational force, resulting in cell aggregation through cell-cell interaction at the bioink reservoir bottom. It significantly undermines the printing performance in terms of droplet formation and post-printing cell distribution, therefore being considered as a critical problem in 3D bioprinting. The previous study has demonstrated the feasibility of circulating bioink to mitigate sedimentation and associated cell aggregation with potentially superior effectiveness. This study focused on construction of sedimentation model to predict the dynamic performance of bioink reservoir in cell distribution considering the influence of cell aggregation in stationary bioink and in circulated bioink. The iterative and time-region-based sedimentation model has been provided, and the influence of cell aggregation has been quantified through least-squares optimization by Nelder-Mead simplex algorithm. The role of cell aggregation in sedimentation of cell-laden bioink during inkjet-based bioprinting has been investigated theoretically and experimentally. It has been discovered that (1) sedimentation model considering single cell underestimates the experimental quantifications of cell concentrations in stationary fluid and overestimates the pump capacity in circulated bioink, while sedimentation model considering cell aggregation generally agrees with both; (2) the formed cell aggregation expedites the cell sedimentation due to the larger size-induced higher sedimentation velocity in stationary bioink; (3) the formed cell aggregation reduces the pump capacity and mitigation effectiveness to cell aggregation in circulated bioink. Applying higher initial cell concentration from 1 × 106to 3 × 106to 5 × 106cell/ml, lower polymer concentration from 1% to 0.5 to 0.25% (w/v) sodium alginate, and longer printing time from 30 to 60 to 90 minutes increase the chance of forming cell aggregates due to greater sedimentation-induced accumulation of cells and shorter distance-induced greater cell-cell interaction.