Post‐Maturation Reinforcement of 3D‐Printed Vascularized Cardiac Tissues

Abstract Despite advances in biomaterials engineering, a large gap remains between the weak mechanical properties that can be achieved with natural materials and the strength of synthetic materials. Here, a method is presented for reinforcing an engineered cardiac tissue fabricated from differentiated induced pluripotent stem cells (iPSCs) and an extracellular matrix (ECM)‐based hydrogel in a manner that is fully biocompatible. The reinforcement occurs as a post‐fabrication step, which allows for the use of 3D‐printing technology to generate thick, fully cellularized, and vascularized cardiac tissues. After tissue assembly and during the maturation process in a soft hydrogel, a small, tissue‐penetrating reinforcer is deployed, leading to a significant increase in the tissue's mechanical properties. The tissue's robustness is demonstrated by injecting the tissue in a simulated minimally invasive procedure and showing that the tissue is functional and undamaged at the nano‐, micro‐, and macroscales.