Collagen modulates functional activity of hepatic cells inside alginate-galactosylated chitosan hydrogel microcapsules

Abstract

To provide comparable hepatic tissue microenvironment and induce functional behavior for hepatocytes, galctosylated-chitosan (GC) as well as collagen (Col) was added to alginate microcapsule coated with extra layer of chitosan. Four different hydrogel groups of alginate/chitosan (AC); alginate-galactosylated chitosan/chitosan (AGC/C); alginate-collagen/chitosan (ACol/C); and alginate-galactosylated chitosan-collagen/chitosan (AGCCol/C) were prepared and characterized for physical properties such as porosity, swelling, degradation rate, and stiffness. Introduction of GC as well as Col to alginate regulated significantly the physical properties of the resultant hydrogels. GC addition decreased dramatically swelling, degradation, pore size and mechanical properties of the resultant hydrogel. However, the influence of GC on the physical properties in the presence of Col (AGCCol/A) was in a reverse manner, as compared to the AGC/C hydrogel. The AGCCol/C microenvironment also promoted proliferation of microencapsulated HepG2 cells, as a model of hepatocyte, compared to the control-matched groups. Biochemical analysis after 10 days revealed a superior effect of AGCCol/C on the secretion of albumin and urea compared to other groups (P < 0.05). These features were coincided with the mRNA up-regulation of P450 and albumin in the AGCCol/C groups compared to the AGC/C and ACol/C groups (P < 0.05). The study demonstrated that enrichment of alginate-based hydrogels with Col and GC could be touted as an appropriate 3D platform for modular hepatic tissue engineering.