Silicon carbide nanowires preserve human atrial microtissue function and show a preliminary reduction of AF duration in an aged-rat atrial tachypacing model
M Miragoli, S Berrettoni, R Statello, W Hong, G Attolini, F Rossi, J Sanchez Alonso Mardones, S Rossi, A Shevchuk, J GorelikAbstract
Background
Atrial fibrillation (AF) remains difficult to treat and current approaches (ablation/antiarrhythmic drugs) may be limited by durability and substrate-altering injury. Semiconductor nanomaterials such as silicon carbide nanowires (SiC-NWs) combine electrical properties with high biocompatibility and could enable non-destructive modulation of atrial electromechanical behavior. However, their interaction with human atrial cardiomyocytes and fibrillating atrial tissue is insufficiently characterized.
Purpose
To assess the effects of SiC-NWs on human stem cell–derived atrial cardiomyocytes in 2D and 3D models, and to explore in vivo feasibility in an AF rat model.
Methods
Human embryonic stem cell–derived atrial cardiomyocytes (hESC-aCMs) were cultured as 2D monolayers and 3D spheroids and exposed to SiC-NWs. Contractility parameters were quantified using the longitudinal optokinematic incubation platform (LOKI), including contraction time, relaxation time, and beat duration, with longitudinal follow-up up to 14 days in 3D spheroids. SiC-NWs localization was assessed by oblique plane microscopy (OPM). Cell membrane nanomechanics were measured by scanning ion-conductance microscopy (SICM). In parallel, inducibility of AF via rapid right-atrial tachypacing were evaluated in 24-month-old rats after left atria intramural injection of SiC-NWs, by means of epicardial grids positioned on atrium and ventricle.
Results
In both 2D monolayers and 3D spheroids, LOKI showed preserved contractility parameters after exposure to SiC-NWs, with no detectable functional alteration during 14-day longitudinal screening in 3D. OPM fluorescence imaging demonstrated SiC-NWs interaction with the cell membrane and suggested intracellular localization. SICM revealed increased membrane stiffness (Young’s modulus ~1073 Pa to ~1292 Pa) after SiC-NWs exposure. In vivo, epicardial recordings showed a marked reduction in AF duration following atrial SiC-NWs administration compared to physiological solution injection (mean AF duration from 660±0 ms to 2201±693 ms, respectively) without evidence of acute electrical instability on ventricular recordings.
Conclusion
SiC-NWs integrate with human atrial cardiomyocytes while preserving contractile function, alter membrane nanomechanics, and provide in vivo evidence of reduced AF burden in an aged-rat atrial tachypacing model. These data support further mechanistic and dose–response studies to define durability and translational potential of SiC-NWs–based atrial substrate modulation.