F Hoffmann-La Roche AG Research and Development Division, Pharmaceutical Sciences, Roche Innovation Center Basel, Grenzacherstrasse 124, Basel, Basel-Stadt CH-4070, Switzerland.
The University of Sydney Faculty of Medicine and Health, Kolling Building, Kolling Institute, St Leonards, Sydney, NSW 2065, Australia.
Biofabrication. 2021 Aug 13;13(4). doi: 10.1088/1758-5090/ac14ca.
Currentandmodels fail to accurately recapitulate the human heart microenvironment for biomedical applications. This study explores the use of cardiac spheroids (CSs) to biofabricate advancedmodels of the human heart. CSs were created from human cardiac myocytes, fibroblasts and endothelial cells (ECs), mixed within optimal alginate/gelatin hydrogels and then bioprinted on a microelectrode plate for drug testing. Bioprinted CSs maintained their structure and viability for at least 30 d after printing. Vascular endothelial growth factor (VEGF) promoted EC branching from CSs within hydrogels. Alginate/gelatin-based hydrogels enabled spheroids fusion, which was further facilitated by addition of VEGF. Bioprinted CSs contracted spontaneously and under stimulation, allowing to record contractile and electrical signals on the microelectrode plates for industrial applications. Taken together, our findings indicate that bioprinted CSs can be used to biofabricate human heart tissues for long termtesting. This has the potential to be used to study biochemical, physiological and pharmacological features of human heart tissue.
当前的模型无法准确再现用于生物医学应用的人类心脏微环境。本研究探索了使用心脏球体（CS）来生物制造人类心脏的先进模型。CS 由人心肌细胞、成纤维细胞和内皮细胞（EC）组成，混合在最佳的藻酸盐/明胶水凝胶中，然后在微电极板上进行生物打印以进行药物测试。生物打印的 CS 在打印后至少 30 天内保持其结构和活力。血管内皮生长因子（VEGF）促进了水凝胶中 CS 内的 EC 分支。基于藻酸盐/明胶的水凝胶使球体融合成为可能，而添加 VEGF 则进一步促进了融合。生物打印的 CS 自发收缩并在受到刺激时收缩，从而可以在微电极板上记录收缩和电信号，可用于工业应用。总之，我们的研究结果表明，生物打印的 CS 可用于生物制造人类心脏组织进行长期测试。这有可能用于研究人类心脏组织的生化、生理和药理学特征。
