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

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.