3D bioprinted cardiac patches for cardiovascular regenerative medicine
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Myocardial infarction (MI) is the leading cause of death worldwide causing irreversible damage to the heart. Despite the incidence and prevalence of MI, current treatments delay the progression of the damage rather than regenerate the function of the cardiac tissue. Over the past years, there has been a rising interest in cardiac tissue engineering, and three-dimensional (3D) bioprinting, to design regenerative approaches to treat damage to the heart caused by MI. Particularly, bioengineered cardiac patches have shown their potential in restoring cardiac tissue structure and function. Regardless of this progress, the clinical application of current cardiac tissue engineering platforms remains limited by shortcomings, ranging from poor vascularization to reduced cellular survival. This study investigated the fabrication of perfusable 3D bioprinted cardiac patches with functional vascular networks. Cardiac patch devices were 3D bioprinted with gelatin methacrylate (gelMA) hydrogel with channels bioprinted using a sacrificial pluronic bioink. The cardiac constructs were seeded with human umbilical vein endothelial cells (HUVECs) and cultured in static, dynamic, and perfusion conditions throughout a two-week period to evaluate in vitro the cellular growth and organization within the channels. The results from this study suggested that the 3D model of the patch was successfully bioprinted with the formation of fully patent and endothelialized channels. Although no significant differences were found in cellular metabolic activity between static and dynamic conditions at all timepoints, perfused cardiac patches showed a decrease in cellular metabolic activity at day 10 and day 14. Furthermore, qualitative results indicated the successful attachment of HUVECs on the channel walls. Overall, these results suggest that the developed cardiac patch devices serve as a potential model to repair and restore in vitro cardiac tissue after MI. In addition, novel 3D bioprinted vascularized cardiac constructs can be used as research enabling an in vitro platform to provide insights into cardiac tissue homeostasis, diseases, and therapies.