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

Abstract

Constructing a cell-inductive scaffold that promotes the proliferation of cardiac-specific host cells for effective myocardium repair is a great challenge in the realm of cardiac tissue engineering. Three-dimensional (3D) printing allows for the 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 (hpcECM) hydrogel 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 levels of 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 in the experiment. 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 high expression of inflammatory genes (CCR7 and IL-1α, expressed after 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 findings highlight hpcECM as a promising immunomodulatory matrix supporting tissue-specific cell attachment and activation; particularly, hydrophobic 3D-printed constructs would outperform equivalents like fibronectin-coated constructs.

Keywords

3D printing / Human placenta chorion ECM / Induced hydrophilicity / Cell adhesion / Immunomodulation

Funding

This 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.