In general,
alginate hydrogels are considered to be biologically inert and are commonly used for biomedical purposes that require minimum
inflammation. However, Ca(2+), which is commonly used to crosslink
alginate, is a critical second messenger in immune cell signaling, and little has been done to understand its effect on immune cell fate when delivered as a component of
alginate gels. We found that dendritic cells (DCs) encapsulated in Ca(2+)-crosslinked
alginate (calcium alginate) secreted at least fivefold more of the inflammatory
cytokine IL-1β when compared to DCs encapsulated in
agarose and
collagen gels, as well as DCs plated on tissue-culture
polystyrene (
TCPS). Plating cells on
TCPS with the
alginate polymer could not reproduce these results, whereas culturing DCs on
TCPS with increasing concentrations of Ca(2+) increased IL-1β, MHC class II and CD86 expression in a dose-dependent manner. In agreement with these findings,
calcium alginate gels induced greater maturation of encapsulated DCs compared to
barium alginate gels. When injected subcutaneously in mice,
calcium alginate gels significantly upregulated IL-1β secretion from surrounding tissue relative to
barium alginate gels, and similarly, the inflammatory effects of LPS were enhanced when it was delivered from
calcium alginate gels rather than
barium alginate gels. These results confirm that the Ca(2+) used to crosslink
alginate gels can be immunostimulatory and suggest that it is important to take into account Ca(2+)'s bioactive effects on all exposed cells (both immune and non-immune) when using
calcium alginate gels for biomedical purposes. This work may strongly impact the way people use
alginate gels in the future as well as provide insights into past work utilizing
alginate gels.