Ultra‐Histocompatible and Electrophysiological‐Adapted PEDOT‐Based Hydrogels Designed for Cardiac Repair

Abstract

Abstract Currently, although conducting polymers have exhibited potential electrophysiological modulation, designing bioinspired ultra‐histocompatible conducting polymers remains a long‐standing challenge. Moreover, the water dispersibility, conductivity, and biocompatibility of conducting polymers are incompatible, which restricts their application in tissue engineering. Herein, a multilevel template dispersion strategy is presented to produce poly(3,4‐ethylenedioxythiophene):(dextran sulfate/carboxymethyl chitosan) (PEDOT:(DSS/CMCS)) with biocompatibility superior to that of commercial poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) without sacrificing processability and conductivity. The PEDOT:(DSS/CMCS) and oxidized dextran solutions form an injectable PEDOT‐based hydrogel (PDCOH) mediated by dynamic covalent imine bonds under mild conditions. The PDCOH has a tissue‐matched modulus and conductivity to adapt to the mechanical environment of dynamic tissue and modulate fibrosis‐induced electrical decoupling. The PDCOH combined with adipose‐derived stem cells demonstrates superior cardiac repair effects over cell suspensions and nonconductive hydrogels, inhibiting ventricular remodeling, reducing fibrous scarring, promoting vascular regeneration, and restoring electrophysiological and pulsatile functions.