Hypoplastic left heart syndrome (HLHS) is a complex congenital heart condition in which a neonate is born with an underdeveloped left ventricle and associated structures. Without palliative interventions, HLHS is fatal. Treatment typically includes medical management at the time of birth to maintain patency of the ductus arteriosus, followed by three palliative procedures: most commonly the Norwood procedure, bidirectional cavopulmonary shunt, and Fontan procedures. With recent advances in surgical management of HLHS patients, high survival rates are now obtained at tertiary treatment centers, though adverse neurodevelopmental outcomes remain a clinical challenge. While surgical management remains the standard of care for HLHS patients, innovative treatment strategies continue to be developing. Important for the development of new strategies for HLHS patients is an understanding of the genetic basis of this condition. Another investigational strategy being developed for HLHS patients is the injection of stem cells within the myocardium of the right ventricle. Recent innovations in tissue engineering and regenerative medicine promise to provide important tools to both understand the underlying basis of HLHS as well as provide new therapeutic strategies. In this review article, we provide an overview of HLHS, starting with a historical description and progressing through a discussion of the genetics, surgical management, post-surgical outcomes, stem cell therapy, hemodynamics and tissue engineering approaches.
The field of biological pumps is a subset of cardiac tissue engineering and focused on the development of tubular grafts that are designed generate intraluminal pressure. In the simplest embodiment, biological pumps are tubular grafts with contractile cardiomyocytes on the external surface. The rationale for biological pumps is a transition from planar 3D cardiac patches to functional biological pumps, on the way to complete bioartificial hearts. Biological pumps also have applications as a standalone device, for example, to support the Fontan circulation in pediatric patients. In recent years, there has been a lot of progress in the field of biological pumps, with innovative fabrication technologies. Examples include the use of cell sheet engineering, self-organized heart muscle, bioprinting and in vivo bio chambers for vascularization. Several materials have been tested for biological pumps and included resected aortic segments from rodents, type I collagen, and fibrin hydrogel, to name a few. Multiple bioreactors have been tested to condition biological pumps and replicate the complex in vivo environment during controlled in vitro culture. The purpose of this article is to provide an overview of the field of the biological pumps, outlining progress in the field over the past several years. In particular, different fabrication methods, biomaterial platforms for tubular grafts and examples of bioreactors will be presented. In addition, we present an overview of some of the challenges that need to be overcome for the field of biological pumps to move forward.
Discrete subaortic stenosis (DSS) is a pediatric condition in which a fibrotic membrane forms within the left ventricular outflow track. The fibrotic membrane is removed surgically; however, there is a high rate of reoccurrence which requires a second surgery. There are currently no tools available to predict the risk of reoccurrence in DSS patients, a limitation addressed by this study. In this study, we analyzed resected fibrotic membranes for DSS patients at the time of first surgery for non-recurrent and recurrent patients, and at the time of second surgery for recurrent patients. RNA-sequencing was conducted to obtain a global screen of changes in RNA expression while mass spectrometry was used to obtain a global screen of changes in protein expression. The results from the RNA-sequencing and mass spectrometry provide valuable insight into genes and the proteins that are differentially regulated in recurrent vs non-recurrent DSS patients.
The aim of this study was to investigate the survival, distribution and reaction of different cell types on a monolayer disk, as well as their behavior under bioreactor treatment. Specifically, porcine EEC and porcine fibroblasts (PCF) were labeled with GFT and Texas Red, respectively, to track their viability and distribution. The experiments involved monitoring the cells using various microscopy techniques and comparing the results with controls. These findings have important implications for understanding cell behavior and potential applications for Discrete Subaortic Stenosis. This paper aims to discuss the implications of the findings in the context of existing literature and future research directions.
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