Injectable conductive chitosan/dextran/polypyrrole hydrogel for cardiac repair with potential application in radiation-induced cardiac injury

Radiation-induced heart damage (RIHD) remains a prevalent and clinically challenging late complication of thoracic radiotherapy, for which effective minimally invasive restorative interventions remain unavailable. Injectable hydrogels are attractive for myocardial repair because they can be delivered through minimally invasive procedures, undergo in situ gelation, and provide a tunable microenvironment that supports tissue regeneration. In this work, we designed an injectable, thermosensitive, and electrically conductive hydrogel composed of chitosan (CS), dextran (DEX), and polypyrrole (PPy). Gelation was achieved via a dual physical cross-linking mechanism that integrates electrostatic interactions between protonated CS and phosphate species from β-GP with hydrogen-bonding interactions primarily between CS and DEX, resulting in a stable three-dimensional porous network with robust mechanical integrity. Incorporation of PPy generated an interpenetrating conductive phase that significantly enhanced charge transport and increased the bulk conductivity to the same order of magnitude as native myocardium. In vitro studies demonstrated that the conductive hydrogel supported the adhesion, spreading, and proliferation of human umbilical vein endothelial cells (HUVECs), while also promoting Ca 2+ signaling, indicating enhanced intercellular communication on an electroactive substrate. Collectively, the CS/DEX/β-GP/PPy hydrogel provides an injectable, mechanically resilient, and electroactive platform with potential for myocardial repair in RIHD and related cardiac injuries.