Epicardial delivery of a conductive membrane synchronizes conduction to reduce atrial fibrillation

• Published in: Journal of controlled release 2022-11, Vol.351, p.847-859
• Main Authors: Zhang, Yi-Chong, Wang, Min-Yao, Zhang, Chong-Yu, Fan, Yun-Fei, Wu, Jun, Li, Shu-Hong, Fu, Anne, Sun, Yu, Yau, Terrance M., Lu, Ting-Hsuan, Sung, Hsing-Wen, Li, Ren-Ke
• Format: Article
• Language: English
• Subjects: Atrial fibrillation; Cardiomyocyte synchronization; Conductive polymer; Epicardial delivery; Myocardial impedance
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2022.09.062

Conductive polymers have been investigated as a medium for the transmission of electrical signals in biological tissues, but their capacity to rewire cardiac tissue has not been evaluated. Myocardial tissue is unique in being able to generate an electrical potential at a fixed rate; this potential spreads rapidly among cells to trigger muscle contractions. Tissue injuries result in myocardial fibrosis and subsequent non-uniform conductivity, leading to arrhythmia. Atrial fibrillation (AF) is the most common sustained arrhythmia, associated with disruption of atrial electrical signaling, which can potentially be restored by the epicardial delivery of conductive polymers. In this work, poly-3-amino-4-methoxybenzoic acid, conjugated to gelatin, is fabricated as a membrane (PAMB-G) to support conductive velocities that are close to that of the myocardium. A cross-linked gelatin membrane (Gelatin) is used as a control. The as-fabricated PAMB-G has similar tensile elasticities, determined using the Young's modulus, as contracting myocardium; it can also transmit electrical signals to initiate cardiac cell and tissue excitation. Delivering PAMB-G onto the atrium of a rat AF model shortens AF duration and improves post-AF recovery for the duration of a 28-day-long study. Atrial tissue in the PAMB-G-implanted group has lower impedance, higher conduction velocity, and higher field potential amplitude than that in the Gelatin-implanted group. Therefore, the as-proposed PAMB-G is a suitable medium for restoring proper cardiac electrical signaling in AF hearts. [Display omitted] •A conductive membrane is successfully formed by conjugating PAMB onto gelatin.•This conductive membrane, PAMB-G, can be delivered epicardially to the atrium.•PAMB-G lowers atrial impedance and re-synchronizes conduction in fibrotic tissue.•PAMB-G improves post-atrial fibrillation recovery and cardiac function.