Translational optoelectronic control of cardiac rhythm in atrial fibrillation

Descrizione del progetto

Controllo optoelettronico del ritmo cardiaco per il trattamento della fibrillazione atriale

Il progetto TransRhythm, finanziato dall’UE, si propone di determinare il potenziale traslazionale del controllo optoelettronico del ritmo cardiaco per la gestione della fibrillazione atriale in quanto aritmia cardiaca più diffusa. I cardiomiociti atriali umani immortalati che esprimono canali ionici fotosensibili saranno utilizzati per progettare modelli 3D di fibrillazione atriale che rispecchiano le dimensioni dell’atrio umano. Per controllare il ritmo optoelettronico del modello è prevista l’integrazione di array multielettrodo e di LED che generano bioelettricità grazie a una precisa illuminazione. I risultati dello studio consentiranno di applicare questo approccio a modelli animali di fibrillazione atriale per determinarne la fattibilità, la sicurezza e le implicazioni terapeutiche. Il progetto si prefigge di stabilire i principi del controllo optoelettronico del ritmo cardiaco e di scoprire nuove intuizioni sui meccanismi e sul trattamento della fibrillazione atriale.

Obiettivo

It’s my conviction that, one day, we will enable the human heart to terminate its own rhythm disturbances and thereby restore its normal rhythm at any place and time. Such acute restoration of cardiac rhythm would not be based on traumatizing electric shocks, but on generation of bioelectricity by the affected heart itself. In order to explore this paradigm-changing approach for ambulatory shock-free control of cardiac rhythm, I will integrate the unique advances of genetic engineering, computer modelling, tissue engineering and micro-optoelectronics. To determine the advanced and translational potential of such optoelectronic heart rhythm control, the most prevalent cardiac arrhythmia will be targeted, atrial fibrillation (AF).
To this purpose, we will first engineer human atrium-sized 3D models of AF from fully functional conditionally immortalized human atrial cardiomyocytes expressing light-gated ion channels. To realize and explore optoelectronic rhythm control in these models, customized multi-electrode-LED arrays (MELAs) will be integrated to gain full control over bioelectricity generation by precisely tailored illumination. Such illumination will be accomplished by a modular interactive optoelectronic system allowing continuous, accurate and realtime monitoring-based activation of specific LEDs in the MELAs. Insights from these studies will guide the application of this approach in pig models of AF to determine its feasibility, safety and therapeutic implications. From design to interpretation, all these studies will be supported by advanced computer simulations to realize an iterative process of optimization for maximum project outcome.
Establishing translational optoelectronic control of cardiac rhythm is expected to break new ground by revealing unique novel insights into AF mechanisms and management. This project could thus provide distinctively innovative therapeutic options, while generating novel tools and concepts in medical research and care.