Evaluating and Improving Biocompatibility of Conductive Polymers for Cardiac Tissue Engineering

Abstract

Conductive polymers (CPs) have gained increasing attention in cardiac tissue engineering (CTE) due to their ability to restore electrical conductivity, enhance cardiomyocyte (CM) function, and support tissue regeneration. Despite significant progress in the field, challenges related to variability in biocompatibility testing protocols, biodegradability, long-term stability, and potential cytotoxicity of CPs continue to hinder their applications. To address this, we reviewed the properties, applications, and biocompatibility of the three most studied CPs: polypyrrole (PPy), poly(3,4-ethylenedioxythiophene) (PEDOT), and polyaniline (PANI) in CTE. We critically assessed current methods for evaluating the biocompatibility of CPs, highlighting limitations in traditional in vitro and in vivo approaches. A comprehensive roadmap was further suggested to guide the evaluation of the biocompatibility of CPs, including material characterization, in vitro cytotoxicity testing with particular emphasis on in vitro 3D human heart model testing platforms of human pluripotent stem cell (hPSC)-derived engineered heart tissues and cardiac organoids, and in vivo evaluation. Additionally, we discussed recent advances in improving the biocompatibility of CPs through hybrid scaffold development, molecular engineering, and surface chemistry modifications. By establishing this standardized framework, this review aims to overcome current biocompatibility barriers and facilitate the improved implementation of CPs in CTE applications.