Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Research Building III, Columbus, OH, 43215, USA.
Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, OH, USA.
Curr Cardiol Rep. 2021 Mar 17;23(5):47. doi: 10.1007/s11886-021-01474-7.
Large-scale tissue engineering of cardiac constructs is a rapidly advancing field; however, there are several barriers still associated with the creation and clinical application of large-scale engineered cardiac tissues. We provide an overview of the current challenges and recently (within the last 5 years) described promising solutions to overcoming said challenges.
The five major criteria yet to be met for clinical application of engineered cardiac tissues are successful electrochemical/mechanical cell coupling, efficient maturation of cardiomyocytes, functional vascularization of large tissues, balancing appropriate immune response, and large-scale generation of constructs. Promising solutions include the use of carbon/graphene in conjunction with existing scaffold designs, utilization of biological hormones, 3D bioprinting, and gene editing. While some of the described barriers to generation of large-scale cardiac tissue have seen encouraging advancements, there is no solution that yet achieves all 5 described criteria. It is vital then to consider a combination of techniques to achieve the optimal construct. Critically, following the demonstration of a viable construct, there remain important considerations to address associated with good manufacturing practices and establishing a standard for clinical trials.
大规模组织工程心脏构建是一个快速发展的领域；然而，在创建和临床应用大规模工程心脏组织方面仍然存在一些障碍。我们概述了当前的挑战以及最近（在过去 5 年内）描述的克服这些挑战的有希望的解决方案。
工程心脏组织临床应用尚未满足的五个主要标准是成功的电化学/机械细胞偶联、心肌细胞的有效成熟、大组织的功能血管化、平衡适当的免疫反应和构建体的大规模生成。有前途的解决方案包括在现有支架设计中使用碳/石墨烯、利用生物激素、3D 生物打印和基因编辑。虽然已经看到一些大规模心脏组织生成的障碍取得了令人鼓舞的进展，但还没有一种解决方案能够达到所有 5 个描述的标准。因此，重要的是要考虑结合多种技术来实现最佳构建体。至关重要的是，在展示可行的构建体之后，仍然需要考虑与良好生产规范相关的重要考虑因素，并为临床试验建立标准。
