Synthetic recovery of impulse propagation in myocardial infarction via silicon carbide semiconductive nanowires

Paola Lagonegro,Jessica Modica,Giancarlo Salviati,Michele Miragoli,Francesca Rossi,Francesco Paolo Lo Muzio,Nicolò Salvarani,Francesca D’Autilia,Gianluigi Condorelli,Martina Quaretti,Franca Bigi,Silvana Pinelli,Rossella Alinovi,Ferdinando Gazza,Stefano Rossi,Daniele Catalucci,Giacomo Rozzi

doi:10.1038/s41467-021-27637-2

Abstract

Myocardial infarction causes 7.3 million deaths worldwide, mostly for fibrillation that electrically originates from the damaged areas of the left ventricle. Conventional cardiac bypass graft and percutaneous coronary interventions allow reperfusion of the downstream tissue but do not counteract the bioelectrical alteration originated from the infarct area. Genetic, cellular, and tissue engineering therapies are promising avenues but require days/months for permitting proper functional tissue regeneration. Here we engineered biocompatible silicon carbide semiconductive nanowires that synthetically couple, via membrane nanobridge formations, isolated beating cardiomyocytes over distance, restoring physiological cell-cell conductance, thereby permitting the synchronization of bioelectrical activity in otherwise uncoupled cells. Local in-situ multiple injections of nanowires in the left ventricular infarcted regions allow rapid reinstatement of impulse propagation across damaged areas and recover electrogram parameters and conduction velocity. Here we propose this nanomedical intervention as a strategy for reducing ventricular arrhythmia after acute myocardial infarction.

Highlights

Myocardial infarction causes 7.3 million deaths worldwide, mostly for fibrillation that electrically originates from the damaged areas of the left ventricle
The STICH (Surgical Treatment of Ischemic Heart Failure) trial showed that the 5-year cumulative incidence of sudden cardiac death (SCD) after coronary artery bypass graft (CABG) was 8.5%2, suggesting that CABG patients, with or without improvement of the left ventricular ejection fraction, may remain at risk of SCD3
Having demonstrated that biophysically inspired Silicon carbide nanowires (SiC-NWs) can synchronize the cellular electrical activity over a distance in vitro via the creation of membrane nanobridges (MNBs), we investigated the possibility of acutely recovering impulse propagation in a 2 × 2 mm cryoinjury area (Cryo)[25,26] of the rat left ventricle, used as a model of acute myocardial infarction (MI) (Fig. 6)

Summary

Introduction

Myocardial infarction causes 7.3 million deaths worldwide, mostly for fibrillation that electrically originates from the damaged areas of the left ventricle. Local in-situ multiple injections of nanowires in the left ventricular infarcted regions allow rapid reinstatement of impulse propagation across damaged areas and recover electrogram parameters and conduction velocity. We propose this nanomedical intervention as a strategy for reducing ventricular arrhythmia after acute myocardial infarction. We demonstrate that injectable and biophysically inspired SiCNWs are capable of electrotonically synchronizing isolated cardiomyocytes via the formation of membrane nanobridges (MNBs)[21] They biophysically regenerate physiological electrical conductance and synthetically restore electrograms (EGs) parameters and impulse propagation in left ventricular MI regions within 5 h following their injection

Methods

Results

Conclusion