Effect of fiber diameter on the assembly of functional 3D cardiac patches

The cardiac ECM has a unique 3D structure responsible for tissue morphogenesis and strong contractions. It is divided into three fiber groups with specific roles and distinct dimensions; nanoscale endomysial fibers, perimysial fibers with a diameter of 1 mu m, and epimysial fibers, which have a diameter of several micrometers. We report here on our work, where distinct 3D fibrous scaffolds, each of them recapitulating the dimension scales of a single fiber population in the heart matrix, were fabricated. We have assessed the mechanical properties of these scaffolds and the contribution of each fiber population to cardiomyocyte morphogenesis, tissue assembly and function. Our results show that the nanoscale fiber scaffolds were more elastic than the microscale scaffolds, however, cardiomyocytes cultured on microscale fiber scaffolds exhibited enhanced spreading and elongation, both on the single cell and on the engineered tissue levels. In addition, lower fibroblast proliferation rates were observed on these microscale topographies. Based on the collected data we have fabricated composite scaffolds containing micro and nanoscale fibers, promoting superior tissue morphogenesis without compromising tissue contraction. Cardiac tissues, engineered within these composite scaffolds exhibited superior function, including lower excitation threshold and stronger contraction forces than tissue engineered within the single-population fiber scaffolds.