A polyphenol-derived redox-active and conductive nanoparticle-reinforced hydrogel with wet adhesiveness for myocardial infarction repair by simultaneously stimulating anti-inflammation and calcium homeostasis pathways

Myocardial infarction (MI) is one major cause of death worldwide. Safe and effective fixation of a functional cardiac patch onto the wet and dynamic myocardium is desired for clinical cardiac repair. Here, we engineered a biodegradable, conductive, and wet-adhesive hydrogel-based cardiac patch, formed by integrating polyphenol-derived redox-active and conductive nanoparticles within a flexible gelatin network. The hydrogel can directly adhere to the infarct area without eliciting a foreign body response. The hydrogel is highly flexible and mechanically resilient to accommodate the diastolic and systolic movements of the myocardium. More importantly, the hydrogel not only works as a structurally and electrically sound bridge to produce effective electrical pulses and synchronize orderly beating in cardiomyocytes but also has an immunomodulatory ability to resolve the early inflammatory response and limit ventricular remodeling. Consequently, the hydrogel simultaneously targets anti-inflammation and calcium homeostasis pathways to mediate cardiac function in both rats and minipigs following MI, which is promising for its translation into clinical practice.