Development of a novel 3D perfusable vascular graft model to elucidate the mechanisms for congenital heart disorders.

Pediatric heart transplantation is hampered by a chronic shortage of donor organs. This problem is further confounded by graft rejection. Identification of earlier indicators of pediatric graft rejection and development of subsequent strategies to counteract these effects will increase the longevity of transplanted pediatric hearts. Heart transplant reject is due to a complex series of events, resulting in CAV, which is thought to be mediated through a host immune response. However, the earlier events leading to CAV are not very well known. We hypothesize that early events related to ischemia reperfusion injury during pediatric heart transplantation are responsible for CAV and subsequent graft rejection. Identification of the molecular markers of ischemia reperfusion injury and development of subsequent therapies to block these pathways can potentially lead to a therapeutic strategy to reduce CAV and increase the longevity of the transplanted heart. To accomplish this goal, we have developed a perfusable vascular graft model populated with endothelial cells and demonstrated the feasibility of this model to understand the early events of ischemia reperfusion injury.

Recent advances in biological pumps as a building block for bioartificial hearts.

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.

Current state of the art in hypoplastic left heart syndrome.

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.