Fabrication of stable galactosylated alginate microcapsules via covalent coupling onto hydroxyl groups for hepatocytes applications

Abstract

Galactose moieties are covalently coupled with sodium alginate to enhance liver-specific functions in microcapsules owing to the specific interaction between the galactose moieties and the asialoglycoprotein receptors (ASGPRs) of hepatocytes. In this study, galactosylated alginate (L-NH2-OH-alginate) based microcapsules with desirable stability and a suitable 3D microenvironment are designed and fabricated for primary hepatocyte applications. The designed L-NH2-OH-alginate is fabricated via the application of ethylenediamine grafted lactobionic acid (L-NH2) onto the hydroxyl groups of sodium alginate so that the negatively charged carboxyl groups intact in L-NH2-OH-alginate can effectively bond with Ca2+ to form a stable three-dimensional gel network; a subsequent reaction with polycations forms a stable membrane of microcapsules. As a result, L-NH2-OH-alginate based microcapsules exhibit an excellent mechanical stability. Moreover, with a higher degree of substitution in L-NH2-OH-alginate (DS 0.41), the hepatocytes entrapped in L-NH2-OH-alginate microcapsules exhibit better viability and well-maintained liver-specific functions.