A localized and sustainable nitric oxide release cardiac patch for myocardial repair

Abstract Myocardial ischemia-reperfusion injury (MIRI) remains a major clinical challenge associated with rapid coronary recanalization, leading to extensive irreversible cardiomyocyte loss. This process is driven by excessive oxidative stress, inflammatory responses, and impaired angiogenesis, ultimately resulting in progressive cardiac dysfunction. Nitric oxide (NO) holds significant therapeutic potential for its anti-inflammatory and pro-angiogenic effects. However, the rapid degradation in vivo limits clinical applications. To address this limitation, we propose a localized and sustained NO delivery strategy for myocardial repair. Here, we developed a collagen-based cardiac patch incorporating S-nitrosoglutathione (GSNO), a NO donor, via a freeze-drying approach. Leveraging the biocompatibility and structural support of collagen, this platform enables localized and sustained NO release within the ischemia-reperfusion microenvironment. In a murine model of MIRI, it conferred significant acute cardioprotection, and its long-term therapeutic efficacy was further validated in a myocardial infarction (MI) model. Additionally, the patch improved cardiac function, attenuated myocardial injury, enhanced angiogenesis, and promoted M2 macrophage polarization in MIRI. It effectively inhibited adverse cardiac remodeling and facilitated neovascularization in MI mice. Collectively, this study presents a localized and sustained NO delivery platform, achieving coordinated anti-inflammatory and pro-angiogenic effects, and highlights its strong translational potential for myocardial repair and broader cardiovascular disease therapies.