title: Biomaterial adjuvant effect is attenuated by anti-inflammatory drug delivery or material selection.
abstract: 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.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive Atlanta, GA 30332, USA.
authors.forename: Lori W
authors.initials: LW
authors.lastname: Norton
authors.forename: Jaehyung
authors.initials: J
authors.lastname: Park
authors.forename: Julia E
authors.initials: JE
authors.lastname: Babensee
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D003907:Dexamethasone / Q000008:administration & dosage* / Q000276:immunology; D056724:Immunity, Humoral; D019344:Lactic Acid / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012685:Sepharose / Q000276:immunology; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D010047:Ovalbumin; D012685:Sepharose