ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Biomaterials
New Frontiers in Porcine Atrioventricular Node Decellularization: Preserving Extracellular Matrix Architecture for Biological Scaffolds New Frontiers in the Biological Cardiac Rhythm Generator: Preserving Atrioventricular Node Architecture in Decellularized Scaffolds
Provisionally accepted
Alice Tomas1,2
Assunta Fabozzo3
Domenico Ventrella4
Nunzia Gallo5
Alberto Elmi6Nicola Pradegan1,3
Lucia Santorelli7
Luisa Vera Muscatello4
Tiziana Palmosi1,2
Agnese Lauroja2Deborah Sandrin2,8
Selena Mimmi9
Ricardo Malvicini10,2
Giada De Lazzari10,2
Enrico Iaccino11
Filippo Romanato2,8
Giuseppe Sarli4
Paolo Grumati12,7Luca Salvatore13
Alessandro Sannino14
Maria Laura Bacci4
Anna Maria Tolomeo1,2*
Gino Gerosa1,2,3- 1Universita degli Studi di Padova Dipartimento di Scienze Cardio-Toraco-Vascolari e Sanita pubblica, Padua, Italy
- 2Instituto di Ricerca Pediatrica Citta della Speranza, Padua, Italy
- 3Azienda Ospedale Universita Padova, Padua, Italy
- 4Universita degli Studi di Bologna Dipartimento di Scienze Mediche Veterinarie, Ozzano dell'Emilia, Italy
- 5Universita del Salento Dipartimento di Ingegneria dell'Innovazione, Lecce, Italy
- 6Universita degli studi di Pisa Dipartimento di Scienze Veterinarie, Pisa, Italy
- 7Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
- 8Universita degli Studi di Padova Dipartimento di Fisica e Astronomia Galileo Galilei, Padua, Italy
- 9Universita degli Studi Magna Graecia di Catanzaro Dipartimento di Scienze Mediche e Chirurgiche, Catanzaro, Italy
- 10Universita degli Studi di Padova Dipartimento di Salute della Donna e del Bambino, Padua, Italy
- 11Universita degli Studi Magna Graecia di Catanzaro Dipartimento di Medicina Sperimentale e Clinica, Catanzaro, Italy
- 12Universita degli Studi di Napoli Federico II Dipartimento di Medicina Clinica e Chirurgia, Naples, Italy
- 13Typeone s.r.l., Calimera, Italy
- 14Università del Salento, Dipartimento di medicina sperimentale, Lecce, Italy
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Cardiac implantable electronic devices are the current standard for managing arrhythmias, yet their use remains limited by device-related mechanical failures, mechanical complications infection risks, 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.
Keywords: Atrioventricular Node, Biological pacemaker, Cardiac scaffold, Decellularized extracellular matrix (dECM), Tergitol-based protocol
Received: 12 Dec 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Tomas, Fabozzo, Ventrella, Gallo, Elmi, Pradegan, Santorelli, Muscatello, Palmosi, Lauroja, Sandrin, Mimmi, Malvicini, De Lazzari, Iaccino, Romanato, Sarli, Grumati, Salvatore, Sannino, Bacci, Tolomeo and Gerosa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Anna Maria Tolomeo
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.