Electroconductive Biohybrid Hydrogel for Enhanced Maturation and Beating Properties of Engineered Cardiac Tissues

Abstract

Cardiac tissue engineering is a promising strategy to treat heart failure. Yet, several issues remain to be resolved including the prevention of arrhythmia caused by inefficient electrical coupling within the graft and between graft and host tissue. Here, a biohybrid hydrogel composed of collagen, alginate, and electroconductive poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is developed that exhibits extracellular matrix–mimetic fibrous structures and enhanced electrical coupling as well and cardiomyocyte maturation. Presence of PEDOT:PSS in the hydrogel improves electrical conductivity and prevents arrhythmia of tissue constructs containing neonatal rat cardiomyocytes. Moreover, it results in increasing beating frequencies reaching more than 200 beats min−1 endogenous frequencies. In addition, cardiomyocytes exhibit increased alignment and density in these constructs, improved sarcomere organization, and enhanced connexin 43 expression, suggesting maturation of the cardiac tissue. Importantly, the here developed electroconductive biohybrid hydrogels also improve maturation and beating properties of human-induced pluripotent stem cell–derived cardiomyocytes. These cells exhibit 1.9 µm near adult sarcomeric length, enhanced beating frequency, increased speed of contraction, and larger contraction amplitude. Collectively, the data demonstrate the potential of this electroconductive biohybrid hydrogel to improve tissue engineering approaches to treat heart failure and possibly diseases of other electrically sensitive tissues.