Electrically conductive hydrogel-based micro-topographies for the development of organized cardiac tissues

Abstract

The dense uniaxially aligned cardiac cytoarchitecture of the myocardium along with electrical and mechanical coupling between the cardiac cells are key factors in the synchronous contractility of the heart. Following myocardial infarction, the organized architecture of the myocardium is disrupted and non-functional scar tissues are produced. Engineered cardiac tissues, developed in hydrogel-based biomaterials, featuring biomimetic topographical cues have shown significant promise for regeneration and repair of injured myocardium. However, currently engineered tissues still do not exhibit an electrically conductive matrix integrated with highly oriented cellular constructs to promote tissue-level functionalities. To address this limitation, we utilized integrated micro- and nano-technologies to develop gelatin methacrylate (GelMA) hydrogel constructs comprised of surface micro-topographies (microgrooves with 50 μm width and depth) incorporated with electrically conductive gold nanorods (GNRs) to provide simultaneous electrical and topographical cues that mimic physiological relevant myocardium function. F-Actin stained images and fluorescent area coverage data revealed the formation of uniform, dense, and highly aligned cardiac tissues on GelMA-GNR hydrogels compared to discrete and disconnected cellular organization on pure GelMA constructs (control group). Immunostaining images of cardiac markers, specifically sarcomeric α-actinin and connexin 43 also showed higher cytoskeletal alignment and enhanced cellular connectivity on GelMA-GNR hydrogels. Tissues formed on both GelMA and GelMA-GNR constructs demonstrated spontaneous contractility from day 4 to 7 of culture. However, only electrically conductive GelMA-GNR cardiac tissues showed a consistent response in changing beat rate as a result of external stimulation. Overall, we demonstrate the enhanced formation of cardiac tissues with superior cellular organization, connectivity, and electrical properties with use of GNRs and microgrooved GelMA hydrogel that may have potential as a functional cardiac patch in the setting of infarcted myocardium.