Fe (III)@TA@IGF-2 microspheres loaded hydrogel for liver injury treatment

Abstract As one of the most commonly used materials in liver tissue engineering, hydrogel has received much attention in recent years. In this work, we prepared a gelatin methacrylate (GelMA)/oxidized hyaluronic acid (OHA)/galactosylated chitosan (Gal-CS)/Fe (III)@TA@IGF-2 200 (TA200) hydrogel loaded with insulin-like growth factor 2 (IGF-2) for regeneration of damaged hepatocytes. Fe (III)@TA microspheres served as carrier to achieve sustained release of IGF-2 to promote hepatocytes regeneration. Galactose ligands could bind to the asialoglycoprotein receptor (ASGPR) on the surface of hepatocytes. Galactosylated chitosan could significantly increase the specific function of hepatocytes. The hydrogel we prepared had a storage modulus of 1100 Pa and was suitable for migration of hepatocytes. The release ratio of IGF-2 could reach up to 90% within 14 days. For carbon tetrachloride (CCl4) induced human hepatic stellate cell line LX2 damage, GelMA/OHA/Gal-CS/TA200 hydrogel could significantly improve the survival of LX2 cells. The expression of HNF-4α and transferrin was detected in LX2 cells treated with hydrogel, indicating that the specific function of the liver was also restored. In summary, the GelMA/OHA/Gal-CS/TA200 hydrogels could be used as new tissue engineering scaffolds for the construction of artificial livers.