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

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.