title: Differential effects of agarose and poly(lactic-co-glycolic acid) on dendritic cell maturation.
abstract: Application of biomaterials in combination products in which the biomaterial is presented to the host with a biological component prompts the need for understanding the biomaterial-associated adjuvant effect in the immune response against antigens associated with such a product. We have previously demonstrated that a polymer commonly used in tissue engineering and vaccine delivery, poly(lactic-co-glycolic acid) (PLGA), exerts an adjuvant effect in vivo, which was supported by PLGA-induced dendritic cell (DC) maturation in vitro. In this study, the effects of agarose and PLGA on DC maturation were compared in vitro to establish differential biomaterial effects. Human monocyte-derived DCs were treated with agarose or PLGA microparticles or films, and their maturation effect was measured as expression of costimulatory and MHC class II molecules, allostimulatory capacity, and proinflammatory cytokine secretion. Direct comparison of DC maturation phenotype indicated that PLGA was a stronger stimulus of DC maturation than agarose, and this maturation was not affected by microparticle phagocytosis. However, agarose-treated DCs showed higher activation of nuclear factor kappaB (NFkappaB) 24 h after the initial stimulation of DCs. Taken together, these results demonstrate differential biomaterial effects on DC maturation, substantiating the maturation effect of PLGA, and provide screening methods for biomaterial adjuvant effect for applications in combination products.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technologyand Emory University, 313 Ferst Drive Atlanta, 30332, USA.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Yoshida
authors.forename: Julia E
authors.initials: JE
authors.lastname: Babensee
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D018929:Cell Culture Techniques / Q000379:methods*; D002849:Chromatography, Gas; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D006016:Glycolates / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid; D013058:Mass Spectrometry; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010587:Phagocytosis; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D012685:Sepharose / Q000737:chemistry*; D013696:Temperature; D023822:Tissue Engineering; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D006016:Glycolates; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012685:Sepharose