In vivo assessment of iPSC-cardiomyocyte loaded auxetic cardiac patches following chronic myocardial infarction.

Abstract

Novel cardiac patch designs achieved by advanced 3D manufacturing continue to have favorable impacts on the repair and regeneration of the myocardium after injury. Briefly, auxetic units with a negative Poisson's ratio have already shown remarkable promise for serving as a next-generation complex scaffold in left ventricular disease. In this study we biofabricated a 3D printed polycaprolactone (PCL) cardiac auxetic patch loaded with high density contractile induced pluripotent stem cell-derived cardiomyocytes (iCMs) and examined the synergist effect of iCM auxetic patches on a chronic myocardial infarct rodent model compared to a stiffer non-auxetic control patch architecture. A week after the induction of a temporary left anterior descending artery ligation, we administered the treatment groups in the form of patch implantation over the ischemic area after initial acute inflammation was complete and prior to granulation tissue formation following the infarct for clinical relevance. Our findings highlight that auxetic patches can provide additional ventricular support and diminished adverse ventricular remodeling, as seen through ejection fraction outputs and histology, and iCM-laden auxetics show localized regenerative potential through increased vascularization compared to controls with no patch or a non-auxetic patch architecture. Exploration on the impact of a negative Poisson's ratio on both global functional outcomes and local therapeutic benefit highlights that iCM-laden auxetics should be further surveyed for other cardiac pathophysiologic conditions, including more in-depth studies on infarction or right ventricular disease.