The association between in vivo physicochemical changes and inflammatory responses against alginate based microcapsules

Application of alginate-polylysine (PLL) capsules for immunoisolation of living cells are suffering from a varying degree of success and large lab-to-lab variations. In this study we show that these differences in success rates can be attributed to alginate dependent essential physicochemical changes of the properties of capsules in vivo that will render the capsules more susceptible to inflammatory responses. Capsule properties were studied before and after implantation by XPS, by immunocytochemistry, and by measuring zeta potentials. We studied a capsule type which provokes for unknown reasons a strong inflammatory response, i.e. high-guluronic (G) alginate capsules and a capsule type with near identical physicochemical properties but which evokes a minimal inflammatory response, i.e. intermediate-G alginate capsules. The cause of the difference in response was a decrease in nitrogen content on high-G capsules due to detachment of PLL in vivo and an increase of the zeta-potential. Our data illustrate an important overlooked phenomena; the physicochemical properties are not necessarily the properties after exposure to the in vivo microenvironment and might induce undesired inflammatory responses and failure of encapsulated cellular grafts.