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Alginate remains the most popular polymer used for cell encapsulation, yet its biocompatibility is inconsistent. Two commercially available alginates were compared, one with 71% guluronate (HiG), and the other with 44% (IntG). Both alginates were purified, and their purities were verified. After 2 days in the peritoneal cavity of C57BL/6J mice, barium (Ba)-gel and calcium (Ca)-gel beads of IntG alginate were clean, while host cells were adhered to beads of HiG alginate. IntG gel beads, however, showed fragmentation in vivo while HiG gel beads stayed firm. The physicochemical properties of the sodium alginates and their gels were thoroughly characterized. The intrinsic viscosity of IntG alginate was 2.5-fold higher than that of HiG alginate, suggesting a greater molecular mass. X-ray photoelectron spectroscopy indicated that both alginates were similar in elemental composition, including low levels of counterions in all gels. The wettabilities of the alginates and gels were also identical, as measured by contact angles of water on dry films. Ba-gel beads of HiG alginate resisted swelling and degradation when immersed in water, much more than the other gel beads. These results suggest that the main factors contributing to the biocompatibility of gels of purified alginate are the mannuronate/guluronate content and/or intrinsic viscosity.

Alginate is widely used for cell microencapsulation and transplantation. There is a lack of standardization of alginate purity and composition. In a previous study, we compared different alginate purification methods and concluded that polyphenol and endotoxin contaminants were eliminated efficiently but residual protein contaminants persisted with all of the methods under evaluation. The objective of this study was to test the hypothesis that residual proteins play a role in the immunogenicity of certain alginate preparations. Using preparative size exclusion chromatography (SEC) and a large scale purification protocol that was derived from the findings obtained with SEC, we substantially decreased the protein content of alginate preparations. When implanted into mouse peritoneum, barium alginate beads made of alginates that were purified using SEC or the derived large scale protocol induced significantly less pericapsular cell adhesion than those made with control alginates. In conclusions, these results suggest that removing residual protein contamination may decrease the immunogenicity of certain alginate preparations. The measurement of proteins could be used as a screening method for evaluating alginate preparations.

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