3D Bioprinted Spheroidal Droplets for Engineering the Heterocellular Coupling between Cardiomyocytes and Cardiac Fibroblasts
3D Bioprinted Spheroidal Droplets for Engineering the Heterocellular Coupling between Cardiomyocytes and Cardiac Fibroblasts
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DOI：
10.34133/2021/9864212
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发表时间：
2021-12-28
影响因子：
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通讯作者：
Joddar, Binata
中科院分区：
文献类型：
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作者：
El Khoury, Raven;Nagiah, Naveen;Joddar, Binata
由于传统的人类心脏二维（2D）细胞培养和多层三维（3D）模型无法重现细胞复杂性并且具有较差的翻译能力，我们设计并开发了具有心肌细胞和心脏成纤维细胞的高通量可扩展的3D生物打印心脏球状液滴-类器官模型，其可用于药物筛选或再生工程应用。这项研究帮助建立了生物打印和交联明胶-藻酸盐基生物墨水的参数，使其成为3D球状液滴。在我们实验室的先前研究中开发的扁平盘状结构用作对照。评估了3D球状液滴的微观结构和机械稳定性，发现其对于心脏支架是理想的。将成人心脏成纤维细胞和AC 16心肌细胞混合在生物墨水中并生物打印。活-死测定和流式细胞术分析揭示了3D球状液滴的稳健生物相容性，其支持长期培养物中心脏细胞的生长和增殖。此外，心肌细胞和心脏成纤维细胞之间的异细胞间隙连接偶联进一步验证了三维心脏球状液滴模型。
Since conventional human cardiac two-dimensional (2D) cell culture and multilayered three-dimensional (3D) models fail in recapitulating cellular complexity and possess inferior translational capacity, we designed and developed a high-throughput scalable 3D bioprinted cardiac spheroidal droplet-organoid model with cardiomyocytes and cardiac fibroblasts that can be used for drug screening or regenerative engineering applications. This study helped establish the parameters for bioprinting and cross-linking a gelatin-alginate-based bioink into 3D spheroidal droplets. A flattened disk-like structure developed in prior studies from our laboratory was used as a control. The microstructural and mechanical stability of the 3D spheroidal droplets was assessed and was found to be ideal for a cardiac scaffold. Adult human cardiac fibroblasts and AC16 cardiomyocytes were mixed in the bioink and bioprinted. Live-dead assay and flow cytometry analysis revealed robust biocompatibility of the 3D spheroidal droplets that supported the growth and proliferation of the cardiac cells in the long-term cultures. Moreover, the heterocellular gap junctional coupling between the cardiomyocytes and cardiac fibroblasts further validated the 3D cardiac spheroidal droplet model.