Institute of Biomedical Engineering, Department of Pharmacology and Physiology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada; Research Center, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, H3T 1C5 Canada; Montreal TransMedTech Institute (iTMT), Montreal, QC H3T 1C5, Canada.
Laboratory for Innovation in Microengineering (LiME), Department of Mechanical Engineering, Center for Biomedical Research, University of Victoria, Victoria, BC V8P 2C5, Canada; Centre for Advanced Materials and Related Technologies (CAMTEC), University of Victoria, Victoria, BC V8P 5C2, Canada.
Biomater Adv. 2022 Jul;138:212916. doi: 10.1016/j.bioadv.2022.212916. Epub 2022 May 23.
Current drug screening approaches are incapable of fully detecting and characterizing drug effectiveness and toxicity of human cardiomyocytes. The pharmaceutical industry uses mathematical models, cell lines, and in vivo models. Many promising drugs are abandoned early in development, and some cardiotoxic drugs reach humans leading to drug recalls. Therefore, there is an unmet need to have more reliable and predictive tools for drug discovery and screening applications. Biofabrication of functional cardiac tissues holds great promise for developing a faithful 3D in vitro disease model, optimizing drug screening efficiencies enabling precision medicine. Different fabrication techniques including molding, pull spinning and 3D bioprinting were used to develop tissue-engineered heart chambers. The big challenge is to effectively organize cells into tissue with structural and physiological features resembling native tissues. Some advancements have been made in engineering miniaturized heart chambers that resemble a living pump for drug screening and disease modeling applications. Here, we review the currently developed tissue-engineered heart chambers and discuss challenges and prospects.
当前的药物筛选方法无法完全检测和描述人类心肌细胞的药物有效性和毒性。制药行业使用数学模型、细胞系和体内模型。许多有前途的药物在开发早期就被放弃,一些心脏毒性药物进入人体导致药物召回。因此,人们迫切需要更可靠和更具预测性的药物发现和筛选应用工具。功能心脏组织的生物制造为开发忠实的 3D 体外疾病模型、优化药物筛选效率以实现精准医学提供了巨大的潜力。不同的制造技术,包括成型、拉伸纺丝和 3D 生物打印,已被用于开发组织工程心脏室。面临的巨大挑战是如何有效地将细胞组织成具有类似于天然组织的结构和生理特征的组织。在工程小型化心脏室方面已经取得了一些进展,这些心脏室类似于用于药物筛选和疾病建模应用的活体泵。在这里,我们综述了目前开发的组织工程心脏室,并讨论了挑战和前景。