Cell-derived extracellular matrix-coated silk fibroin scaffold for cardiogenesis of brown adipose stem cells through modulation of TGF-β pathway

The cell-derived extracellular matrix(ECM)-modified scaffolds have advantages of mimic tissue specificity and been thought to better mimic the native cellular microenvironment in vitro.ECM derived from cardiac fibroblasts(CFs)are considered as key elements that provide a natural cell growth microenvironment and change the fate of cardiomyocytes(CMs).Here,a new hybrid scaffold is designed based on silk fibroin(SF)scaffold and CFs-derived ECM.CFs were seeded on the SF scaffold for 10days culturing and decellularized to produce CFs-derived ECM-coated SF scaffold.The results showed that the cell-derived ECM-modified silk fibroin scaffold material contained collagen,laminin,fibronectin and other ECM components with myocardial-like properties.Further to explore its effects on brown adipose stem cells(BASCs)differentiation into CMs.We found that the CFderived ECM-coated scaffold also increased the expression of CM-specific proteins(e.g.cardiac troponin T and α-actinin)of BASCs.Notably,the b1-integrin-dependent transforming growth factor-β1 signaling pathway was also involved in the regulation of CF-derived ECM by promoting the differentiation of BASCs into CMs.Overall,these findings provide insights into the bionic manufacturing of engineered cardiac tissues(ECTs)and establish a theoretical basis for the construction of ECTs.