Promotion of Cardiac Microtissue Assembly Within G-Csf-Enriched Collagen I-Cardiogel Hybrid Hydrogel Publisher



H Khodayari HAMID ; S Khodayari SAEED ; M Rezaee MALIHE ; S Rezaeiani SIAMAK ; Ma Choshali Mahmoud ALIPOUR ; S Erfanian SAEIDEH ; A Muhammadnejad AHAD ; F Nili FATEMEH ; Y Pourmehran YASAMAN ; R Pirjani REIHANEH
Source: Regenerative Biomaterials Published:2024

Abstract

Tissue engineering as an interdisciplinary field of biomedical sciences has raised many hopes in the treatment of cardiovascular diseases as well as development of in vitro three-dimensional (3D) cardiac models. This study aimed to engineer a cardiac microtissue using a natural hybrid hydrogel enriched by granulocyte colony-stimulating factor (G-CSF), a bone marrow-derived growth factor. Cardiac ECM hydrogel (Cardiogel: CG) was mixed with collagen type I (ColI) to form the hybrid hydrogel, which was tested for mechanical and biological properties. Three cell types (cardiac progenitor cells, endothelial cells and cardiac fibroblasts) were co-cultured in the G-CSF-enriched hybrid hydrogel to form a 3D microtissue. ColI markedly improved the mechanical properties of CG in the hybrid form with a ratio of 1:1. The hybrid hydrogel demonstrated acceptable biocompatibility and improved retention of encapsulated human foreskin fibroblasts. Co-culture of three cell types in G-CSF enriched hybrid hydrogel, resulted in a faster 3D structure shaping and a wellcellularized microtissue with higher angiogenesis compared to growth factor-free hybrid hydrogel (control). Immunostaining confirmed the presence of CD31þ tube-like structures as well as vimentinþ cardiac fibroblasts and cTNTþ human pluripotent stem cells-derived cardiomyocytes. Bioinformatics analysis of signaling pathways related to the G-CSF receptor in cardiovascular lineage cells, identified target molecules. The in silico-identified STAT3, as one of the major molecules involved in G-CSF signaling of cardiac tissue, was upregulated in G-CSF compared to control. The G-CSF-enriched hybrid hydrogel could be a promising candidate for cardiac tissue engineering, as it facilitates tissue formation and angiogenesis. © 2024 Elsevier B.V., All rights reserved.