AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.6383
RESEARCH ARTICLE
Early Access

3D printed cardiac patch coated with human extracellular matrix hydrogel: Significant improvement of cell adhesion and immune reaction

Marjan Enayati1,2* Christopher Riedmüller1,2 Sabrina Rohringer1,2 Lukas Weber1 Felix Pointner1 Luis Pichelkastner1 Marta Bonora3 Ana Isabel Antunes Goncalves1 Francesco Moscato2,3,4 Ewald Unger2,3 Emir Benca5 Marvin Dötzlhofer1 Bruno K. Podesser1,2 Karl H. Schneider1,2,4 Helga Bergmeister1,2
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1 Center for Biomedical Research and Translational Surgery, Medical University Vienna, Austria
2 Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria
3 Center for Medical Physics and Biomedical Engineering, Medical University Vienna, Austria
4 Austrian Cluster for Tissue Regeneration, Vienna, Austria
5 Department of Orthopedics and Trauma Surgery, Division of Orthopedics, Medical University Vienna, Austria
Submitted: 21 November 2024 | Accepted: 2 January 2025 | Published: 2 January 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Cardiac tissue engineering faces a great challenge to construct a cell-inductive scaffold encouraging the proliferation of cardiac-specific host cells for effective myocardium repair. 3D printing allows precise fabrication of intricate structures like cardiac patches but produces large pores (sub-macron), reducing surface area for cell attachment and tissue regeneration. Moreover, the hydrophobic nature of most polyesters used in 3D printing further complicates cell adhesion and integration. In this study, human chorion placenta extracellular matrix hydrogel (hpcECM) with highly preserved ECM components, such as glycosaminoglycans (GAG), elastin and collagen was coated on a hydrophobic 3D-printed poly-ε–caprolactone (PCL) patch. The presence of hpcECM on the 3D-printed PCL patches could significantly induce higher cell attachment, proliferation and activation of cells such as human umbilical vein endothelial cells (HUVECs), endothelial progenitor cells (EPCs), H9c2 undifferentiated/differentiated cardiomyoblasts and fibroblasts. Fibronectin coated samples served as controls. Coating efficiency, hpcECM modulus of elasticity (in nanoscale), surface profile roughness and contact angle measurements were performed and confirmed the significant potential of hpcECM as a stable, soft, hydrophilic coating matrix with low modulus of elasticity for 3D printed synthetic constructs. Furthermore, hpcECM could modulate the inflammation (CCR7 and IL-1α expressions, 72 hours) via high expression of IL-10 in macrophages after one week. Expression of adhesion molecules (ICAM, VCAM-1 and PECAM-1), and hemolysis rate did not show statistically significant changes. All these highlight hpcECM as a promising immunomodulatory matrix, supporting tissue-specific cell attachment and activation, particularly for hydrophobic 3D-printed constructs, outperforming competitors like fibronectin.

Keywords
3D printing
Human placenta chorion ECM
Induced hydrophilicity
Cell adhesion
Immunomodulation
Funding
The study was partly funded by the Ludwig Boltzmann Institute for Cardiovascular Research and by the Optiflow 3D project funded by the Austrian Research Promotion Agency (FFG) Nr. FO999891239.
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing