Silk fibroin electrospun scaffolds with sustained dual release of growth factors enhance acute liver failure treatment

Abstract

Acute liver failure (ALF) is a critical disease with a rapid onset and a high mortality rate despite its low occurrence. Therefore, it is urgent to seek an efficient treatment strategy for ALF. Recently, the liver tissue engineering (LTE) based method has become a promising and emerging technology for ALF treatment. For improving its repair effect, herein, the pure regenerated silk fibroin (RSF) scaffold or RSF scaffold loaded with the hepatocyte growth factor (HGF) and fibroblast growth factor-4 (FGF-4) (named RSF/HGF/FGF-4 scaffold) were constructed from RSF aqueous solution by electrospinning technique. The aqueous system effectively maintains the activity of growth factors. HGF and FGF-4 could be controlled and sustained released from RSF/HGF/FGF-4 scaffold. Compared with pure RSF scaffold, the hydrophilicity and cytocompatibility of RSF/HGF/FGF-4 scaffold were significantly improved. Furthermore, RSF/HGF/FGF-4 scaffold also significantly promoted the hepatogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs), even better than the group with directly adding growth factors in culture medium. In addition, the RSF/HGF/FGF-4 scaffolds seeded with ADSCs achieved an optimal liver function repair effect after the complex was implanted onto the surface of the injured liver in the ALF mice model. The effect was also much better than that of the scaffold without sustained growth factor releasing function. The developed RSF electrospun scaffold with sustained dual release of growth factors showed great application potential for the treatment of ALF.