Injectable Conductive Hydrogel Enabling Sustained Nitric Oxide Generation for Cardiac Tissue Regeneration

Abstract

Cardiovascular diseases remain a major clinical challenge, as existing therapeutic interventions, such as pharmacological agents, cardiac implants, or surgical procedures, offer limited efficacy due to the heart’s inherently low regenerative capacity. To address this, injectable conductive hydrogels capable of delivering bioactive signals and supporting electrical conduction have emerged as promising therapeutic platforms. In this study, a multifunctional hydrogel was developed based on gelatin–tannic acid (GTA), graphene oxide (GO), and copper ions (Cu²⁺), designed for in situ gelation, sustained nitric oxide (NO) release, and tissue-relevant conductivity.The hydrogel was fabricated through a one-step crosslinking strategy, with Cu²⁺ acting as both a crosslinking agent and a catalyst for NO generation from endogenous S-nitrosothiols, while GO contributed to structural integrity and electrical conductivity (1.06 mS/cm). The system achieved prolonged NO release (209.494 µM over 21 days) under physiological conditions. Physicochemical and mechanical properties were characterized using FT-IR, SEM/EDX, rheological analysis, and tissue adhesion tests. In vitro evaluations demonstrated excellent cytocompatibility, enhanced cellular proliferation, stimulation of angiogenesis, and anti-inflammatory effects, collectively representing key biological attributes required for effective cardiac tissue regeneration. These biological responses, combined with its structural integrity and electrical conductivity, represent essential features for cardiac tissue regeneration. Although specific in vitro evaluations of electroconductive signaling remain ongoing, the current findings establish a promising foundation for the development of bioelectronic platforms in myocardial repair. This study thus offers a preliminary yet compelling approach toward minimally invasive treatment strategies for ischemic cardiovascular diseases.