Inflammatory and hemostatic activation induced by alginate microcapsules reveals novel mechanisms underlying their biocompatibility

Abstract Body: Alginate microcapsules for pancreatic beta cells transplantation in diabetes treatment suffers from bioincompatibility problems in terms of fibrotic overgrowth leading to non-functional beta cells. Inflammation is an important factor that determines the biocompatibility of biomedical devices, and surface activation of complement and coagulation proteins might be involved. The whole blood model based on specific thrombin inhibition by lepirudin has proven to be an efficient tool in revealing the pathways of inflammation induced by the various compositions of microcapsules. The aim of the present study was to investigate the cross-talk mechanisms between the complement- and the coagulation systems in this whole blood model. The results showed that the composition of the capsules was critical for the mode of activation. Poly-L-lysine containing microcapsules activated both the complement- and the coagulation systems, the latter mediated through the tissue factor pathway. Cellulose-sulfate containing microcapsules were early and potent activators of coagulation. Poly-L-lysine containing microcapsules with citrate solubilizing the alginate core induced an increased C5 activation compared to their solid counterparts, but with a lower cytokine response. Finally, our data indicate that the cytokine release is dependent on cell-adhesion to the biomaterial surface mediated by the complement iC3b/CD11b interaction. In conclusion, these data indicate a differential effect on complement, coagulation and the cytokine network depending on the composition of the microcapsules and that C3 activation is an important endogenous mediator for the early inflammatory response induced by alginate capsules. Aegean Conferences Series - Vol 86, abstract 21