Bioprinting of cardiac patches with gold-nanowires and tri-culture system for the treatment of myocardial infarction

Myocardial infarction (MI) irreversibly damages cardiac tissues, necessitating advanced therapeutic strategies for effective regeneration. Although cell-based strategies, including bioprinting, have been explored to restore the infarcted tissues, several challenges remain, including limited cellular responses and insufficient paracrine effects. To address these issues, we bioprinted a collagen-based three-dimensional (3D) cardiac patch incorporating aligned gold-nanowires (AuNWs) and a tri-cellular system comprising cardiomyocytes (CMs), cardiac fibroblasts (CFs), and endothelial progenitor cells (EPCs). The concentration of AuNWs, bioprinting parameters, and ratio of the three cell types were optimized by evaluating cellular maturation and signaling factor secretion. Using an appropriate bioink formulation and bioprinting parameters, we successfully fabricated a 3D cardiac patch containing aligned AuNWs and CM/CF/EPC. In vitro studies demonstrated the synergistic effects, including cell alignment, integrin-mediated signaling, focal adhesion kinase formation, and abundant secretion of paracrine factors. These enhancements facilitated the formation of vascularized myocardium during the cultivation of bioprinted cardiac patches. Upon transplantation into rat MI models, the bioengineered 3D cardiac patch significantly accelerated cardiac tissue regeneration by enhancing vascularization and myocardial formation through paracrine effects. These findings highlight the potential of AuNW-assisted bioprinted cardiac patches with a tri-cell culture system as a promising therapeutic platform for tissue regeneration after MI. • A 3D cardiac patch was bioprinted using gold-nanowire-assisted collagen bioink. • Tri-cellular system (CMs, CFs, EPCs) was integrated to enhance cellular crosstalks. • Paracrine factor secretion was synergistically promoted in the 3D cardiac patch. • The bioprinted cardiac patch facilitated vascularized myocardium formation in vitro. • Patch-treatment improved cardiac repair in MI rats via enhanced paracrine effects.