Improvement of the biocompatibility of alginate/poly-L-lysine/alginate microcapsules by the use of epimerized alginate as a coating

Abstract

Alginate/poly-L-lysine(PLL)/alginate capsules are used widely for the microencapsulation of cells. Alginate consists of guluronic acid and mannuronic acid, the ratio and sequence of which affect the properties of the alginate. Using C5-epimerases, mannuronic acid can be converted to guluronic acid in the alginate polymer. Such an enzyme, AlgE4, was used to convert blocks of mannuronic acid (M-blocks) to blocks of alternating sequence (MG-blocks). The aims of this study were 1) to investigate whether the use of epimerized alginate as a coating could improve the biocompatibility of alginate/PLL/alginate capsules and 2) to study the biocompatibility of simple alginate beads prepared with epimerized alginate. Four different capsules, two of which contained epimerized alginate, were investigated after implantation in C57BL/6 mice for 1 week. The biocompatibility of alginate/PLL/alginate capsules, as measured by retrieval rates of the capsules and DNA contents and glucose oxidation rates of the cellular overgrowth, was improved when an epimerized coating alginate was used. There were, however, no statistically significant differences in the biocompatibility of simple alginate beads made from epimerized alginate when compared with non-epimerized alginate beads. In general, such beads produced without a PLL coating swelled to a higher extent than the conventional alginate/PLL/alginate capsules. In conclusion, the use of an epimerized coating on alginate-PLL-alginate can improve the biocompatibility of such capsules but still cannot completely eliminate the detrimental effects of PLL on the biocompatibility of the capsules.