Yu-Chun Chang1,2, Gabriel Mirhaidari1,2, John Kelly1,3,4, Christopher Breuer5,6,7. 1. Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Research Building III, Columbus, OH, 43215, USA. 2. Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, OH, USA. 3. Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA. 4. The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA. 5. Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Research Building III, Columbus, OH, 43215, USA. Christopher.breuer@nationwidechildrens.org. 6. Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Christopher.breuer@nationwidechildrens.org. 7. Department of Surgery, Nationwide Children's Hospital, Columbus, OH, USA. Christopher.breuer@nationwidechildrens.org.
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.
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