New Frontiers in the Biological Cardiac Rhythm Generator: Preserving Atrioventricular Node Architecture in Decellularized Scaffolds

Cardiac implantable electronic devices are the current standard for managing arrhythmias, yet their use remains limited bydevice-related mechanical failures , infection risk, and suboptimal long-term biocompatibility. Developing a biological alternative capable of restoring intrinsic pacemaking function therefore represents an important clinical and technological challenge. In this study, we report the development of a bioengineered cardiac scaffold derived from porcine atrioventricular nodes. A Tergitol-based decellularization protocol was optimized to achieve complete removal of cellular and nuclear components while preserving the three-dimensional architecture and key extracellular matrix constituents. Comprehensive morphological, ultrastructural, proteomic and mechanical analyses confirmed ECM integrity and maintenance of structural organization, including collagen preservation with mild fiber realignment. These results demonstrate that the proposed decellularization strategy yields an ECM scaffold that retains the native features essential for supporting pacemaker tissue architecture. This work lays the groundwork for the creation of next-generation, tissue-derived cardiac scaffolds, with ongoing efforts directed toward ECM-derived hydrogel fabrication, cytocompatibility evaluation, and future integration with cardiomyocytes for biologically inspired pacemaker applications.