Bioprinting microfabricated anisotropic myobundles towards the scaled generation of 3D cardiac tissue

Abstract

The excessive extracellular matrix (ECM) remodeling that occurs following myocardial infarction (MI) causes tissue stiffening and leads to the formation of disorganized and non-contractile scar tissue in place of previously functional myocardium. The field of cardiac tissue engineering aims to create 3D cardiac tissues to model the healthy and diseased heart and investigate regenerative therapies. In the healthy myocardium, cardiomyocytes (CM) form anisotropic cell bundles interspersed with capillaries and cardiac fibroblasts; we aim to recapitulate this structure in vitro for a regenerative therapy following MI. Previously in our lab, we used a small-scale microfluidic platform to generate elongated hydrogels with aligned synthetic fibers and CMs, or ‘myotubes.’ However larger-scale fabrication is needed to generate enough tissues for a complete, millimeter-scale 3D cardiac tissue construct. 3D bioprinting is rapidly emerging as a powerful technology in translational medicine and can be used to generate tissues at higher throughput. This work aims to develop a scalable approach towards creating 3D vascularized cardiac patches to regenerate diseased cardiac tissue using 3D bioprinting.