High throughput direct 3D bioprinting in multiwell plates
High throughput direct 3D bioprinting in multiwell plates
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DOI：
10.1088/1758-5090/ab89ca
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发表时间：
2021-04-01
期刊：
影响因子：
9
通讯作者：
Chen, Shaochen
中科院分区：
文献类型：
--
作者：
Hwang, Henry H.;You, Shangting;Chen, Shaochen
三维（3D）生物打印技术的进步使生物和医疗应用的复杂3D组织支架的制造成为可能，在这些应用中，高速、高通量的孔板生产是一个关键的需求。在这里，我们提出了一个基于微尺度连续光学打印的集成3D生物打印平台，能够在多孔板格式下高通量原位快速制造复杂的3D生物医学样品，以供后续培养和分析。我们的高通量3D生物打印机（HT-3DP）被用来展示不同的空间几何结构的仿生意义，可调的机械性能，以及再现性。在多孔板中原位制备肝癌活体3D组织支架，并对化疗药物阿霉素进行功能药物反应试验。包括活肝细胞癌和人脐静脉内皮细胞在内的双细胞型群体也被打印出来，以证明双组织制造能力。这项工作表明，具有可控空间结构和机械性能的3D生物打印组织支架的生产速度现在可以在高通量规模上完成，从而能够在传统的多孔细胞培养板中快速生成体外3D组织模型，用于高通量临床前药物筛选和疾病建模。
Advances in three dimensional (3D) bioprinting have enabled the fabrication of sophisticated 3D tissue scaffolds for biological and medical applications, where high speed, high throughput production in well plates is a critical need. Here, we present an integrated 3D bioprinting platform based on microscale continuous optical printing, capable of high throughput in situ rapid fabrication of complex 3D biomedical samples in multiwell plate formats for subsequent culture and analysis. Our high throughput 3D bioprinter (HT-3DP) was used to showcase constructs of varying spatial geometries of biomimetic significance, tunable mechanical properties, as well as reproducibility. Live hepatocellular carcinoma 3D tissue scaffolds were fabricated in situ in multiwell plates, after which a functional drug response assay against the chemotherapy drug doxorubicin was performed. Dual cell-type populations involving both live hepatocellular carcinoma as well as human umbilical vein endothelial cells were also printed to demonstrate dual-tissue fabrication capability. This work demonstrates a significant advancement in that the production rate of 3D bioprinted tissue scaffolds with controllable spatial architectures and mechanical properties can now be done on a high throughput scale, enabling rapid generation of in vitro 3D tissue models within conventional multiwell cell culture plates for high throughput preclinical drug screening and disease modeling.