Miao Tingkuan, Chen Keke, Wei Xiaoyun, Huang Beisi, Qian Yuecheng, Wang Ling, Xu Mingen
School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China.
Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province, Hangzhou Dianzi University, Hangzhou 310018, China.
Int J Bioprint. 2023 Apr 17;9(4):733. doi: 10.18063/ijb.733. eCollection 2023.
Acoustic cell assembly devices are applied in cell spheroid fabrication attributed to their rapid, label-free and low-cell damage production of size-uniform spheroids. However, the spheroids yield and production efficiency are still insufficient to meet the requirements of several biomedical applications, especially those that require large quantities of cell spheroids, such as high-throughput screening, macro-scale tissue fabrication, and tissue repair. Here, we developed a novel 3D acoustic cell assembly device combined with a gelatin methacrylamide (GelMA) hydrogels for the high-throughput fabrication of cell spheroids. The acoustic device employs three orthogonal piezoelectric transducers that can generate three orthogonal standing bulk acoustic waves to create a 3D dot-array (25 × 25 × 22) of levitated acoustic nodes, enabling large-scale fabrication of cell aggregates (>13,000 per operation). The GelMA hydrogel serves as a supporting scaffold to preserve the structure of cell aggregates after the withdrawal of acoustic fields. As a result, mostly cell aggregates (>90%) mature into spheroids maintaining good cell viability. We further applied these acoustically assembled spheroids to drug testing to explore their potency in drug response. In conclusion, this 3D acoustic cell assembly device may pave the way for the scale-up fabrication of cell spheroids or even organoids, to enable flexible application in various biomedical applications, such as high-throughput screening, disease modeling, tissue engineering, and regenerative medicine.
声学细胞组装装置因其能快速、无标记且低细胞损伤地产生尺寸均匀的球体而被应用于细胞球体的制造。然而，球体的产量和生产效率仍不足以满足一些生物医学应用的需求，特别是那些需要大量细胞球体的应用，如高通量筛选、宏观组织制造和组织修复。在此，我们开发了一种新型的三维声学细胞组装装置，它与甲基丙烯酰化明胶（GelMA）水凝胶相结合，用于高通量制造细胞球体。该声学装置采用三个正交的压电换能器，可产生三个正交的驻体声波，以创建一个由悬浮声学节点组成的三维点阵列（25×25×22），从而能够大规模制造细胞聚集体（每次操作>13,000个）。GelMA水凝胶作为一种支撑支架，在撤去声场后保持细胞聚集体的结构。结果，大多数细胞聚集体（>90%）成熟为球体，并保持良好的细胞活力。我们进一步将这些通过声学组装的球体应用于药物测试，以探索它们在药物反应中的效力。总之，这种三维声学细胞组装装置可能为细胞球体甚至类器官的规模化制造铺平道路，从而能够灵活应用于各种生物医学应用，如高通量筛选、疾病建模、组织工程和再生医学。
