Silk Fibroin Scaffolds Loaded with Growth Factors Can Reverse Liver Fibrosis

Abstract

Currently, there are no effective pharmacological interventions in clinical practice to reverse liver fibrosis. This study explores the therapeutic potential of regenerated silk fibroin (RSF) scaffolds loaded with dual growth factors for reversing hepatic fibrosis. A chronic liver fibrosis mouse model was induced using carbon tetrachloride (CCl₄) combined with a high-fat diet. RSF scaffolds, with or without hepatocyte growth factor (HGF) and fibroblast growth factor-4 (FGF-4), were implanted onto the liver surface to assess antifibrotic efficacy. Liver function was evaluated using biochemical analysis. Compared with controls, the RSF/HGF/FGF-4 group showed significantly reduced serum levels of C-reactive protein (CRP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histopathological analyses (H&E and Masson's trichrome staining) on days 7, 14, 30, and 60 demonstrated marked improvements in liver architecture and a significant reduction in fibrosis (SAF scores, P < 0.05). Immunohistochemistry further revealed neovascularization and bile duct formation by day 14. Transcriptomic profiling showed upregulation of bile duct development pathways and downregulation of inflammatory signaling. Quantitative PCR confirmed increased expression of bile secretion genes (FXR, OAT) and decreased expression of NF-κB pathway genes (TRAF2, Bax). These findings highlight the RSF/HGF/FGF-4 scaffold as a promising cell-free strategy for promoting functional liver regeneration and reversing chronic liver fibrosis.