Vascular endothelial growth factor (VEGF) and dexamethasone (DX) release from hydrogel coatings were examined as a means to modify tissue inflammation and induce angiogenesis. Antibiofouling hydrogels for implantable glucose sensor coatings were prepared from 2-hydroxyethyl methacrylate, N-vinyl pyrrolidinone, and polyethylene glycol. Microdialysis sampling was used to test the effect of the hydrogel coating on glucose recovery. VEGF-releasing hydrogel-coated fibers increased vascularity and inflammation in the surrounding tissue after 2 weeks of implantation compared to hydrogel-coated fibers. DX-releasing hydrogel-coated fibers reduced inflammation compared to hydrogel-coated fibers and had reduced capsule vascularity compared to VEGF-releasing hydrogel-coated fibers. Hydrogels that released both VEGF and DX simultaneously also showed reduced inflammation at 2 weeks implantation; however, no enhanced vessel formation was observed indicating that the DX diminished the VEGF effect. At 6 weeks, there were no detectable differences between drug-releasing hydrogel-coated fibers and control fibers. From this study, hydrogel drug release affected initial events of the foreign body response with DX inhibiting VEGF, but once the drug depot was exhausted these effects disappeared.

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Biomaterials have been shown to differentially support dendritic cell (DC) maturation, a prerequisite for an adjuvant effect. Treatment of DCs with poly(D,L-lactic-co-glycolic acid). (PLGA) films resulted in DC maturation but agarose films did not. In these studies, the biomaterial adjuvant effect was attenuated by material selection (PLGA or agarose scaffolds) or local delivery of an anti-inflammatory/immunosuppressive glucocorticoid, dexamethasone (DX), from PLGA scaffolds. Porous scaffolds (SCs) of PLGA or agarose were produced to deliver equivalent amounts of model antigen, ovalbumin (OVA). Alternatively, PLGA SCs with incorporated OVA were produced with or without DX. These SCs were implanted individually, subcutaneously, and dorsally in C57BL/6 mice. Blood was collected from mice at specific times over a 12-week duration for measurement of antibody production against OVA. Scaffolds were explanted at 12 weeks for histological examination of foreign body response. Scaffolds of PLGA, but not of agarose, were found to elicit higher antibody production against co-delivered OVA, than negative controls. Short term delivery of DX from PLGA SCs delivering OVA temporarily delayed onset of anti-OVA antibody production. More sustained release of DX at an effective dose and with an appropriate time course is expected to extend the effect of DX on the biomaterial adjuvant effect. The immunomodulatory ability of biomaterials to affect the immune response to co-delivered antigen is demonstrated wherein this immunomodulatory ability correlates with the observed in vitro differential effects of biomaterials on DC maturation.

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