Supramolecular antioxidant conductive injectable hydrogel encapsulating L-arginine for synergistic modulation of myocardial infarction

Currently, injectable hydrogels with multiple desired merits that could modulate specific pathological events have emerged as a revolutionary therapeutic strategy for myocardial infarction (MI) treatment. Despite the promising outcomes of injectable hydrogels with antioxidant, conductivity, and pro-angiogenesis therapeutic efficacy, there are very limited reports on the fabrication of injectable hydrogels integrating the above merits to comprehensively address the multifaceted challenges of MI treatment, particularly using a simplified fabrication methodology. In this study, 2,3,4-trihydroxybenzaldehyde and ferric iron coordination compound was employed as a versatile building block for the supramolecular multifunctional hydrogel. This approach facilitated crosslinking of the hydrogel network via dynamic Schiff base, simultaneously endowing the hydrogel with injectability and antioxidant properties, while also allowing for the loading of the pro-angiogenic agent L-arginine through dynamic covalent bonding. Aniline tetramer grafted gelatin and adipic dihydrazide modified hyaluronic acid were combined with the coordination compound to construct a biodegradable hydrogel with conductivity. After being injected into the infarcted myocardium, this hydrogel could effectively ameliorate the pathologic progression of MI and improve cardiac function, as manifested by significantly reduced infarcted area and collagen deposition, enhanced cardiomyocyte viability and electrical coupling, as well as improved angiogenesis. The study reports, for the first time, an injectable hydrogel integrating antioxidant, conductivity, and pro-angiogenesis via a facile method that could comprehensively target key pathologic events in MI and demonstrate appreciable therapeutic efficacy in MI treatment.