New frontiers in porcine atrioventricular node decellularization: preserving extracellular matrix architecture for biological scaffolds

Introduction: Cardiac implantable electronic devices manage arrhythmias but are limited by mechanical failures, infection risks, and poor long-term biocompatibility. Developing a biological alternative that restores intrinsic pacemaking remains a key clinical challenge. Methods: We developed cardiac scaffolds from porcine atrioventricular nodes using an optimized Tergitol-based decellularization protocol. Morphological, ultrastructural, proteomic, and mechanical analyses were conducted to assess ECM integrity and preservation of native architecture. Results: The decellularization process effectively removed cellular and nuclear components while preserving three-dimensional structure, collagen content, and overall ECM organization. Analyses confirmed that key features essential for pacemaker tissue support were maintained. Discussion: Our findings demonstrate that the scaffold retains native characteristics suitable for biologically inspired pacemaker applications. This work provides a foundation for ECM-derived hydrogel development, cytocompatibility testing, and integration with cardiomyocytes in next-generation tissue-engineered cardiac scaffolds.