No abstract

Macrophages (Mϕ) and dendritic cells (DCs) are critical antigen presenting cells that play pivotal roles in host responses to biomaterial implants. Although Mϕs have been widely studied for their roles in the inflammatory responses against biomaterials, the roles that DCs play in the host responses toward implanted materials have only recently been explored. DCs are of significant research interest because of the emergence of a large number of combination products that cross-traditional medical device boundaries. These products combine biomaterials with biologics, including cells, nucleic acids, and/or proteins. The biomaterial component may evoke an inflammatory response, primarily mediated by neutrophils and Mϕs, whereas the biologic component may elicit an immunogenic immune response, initiated by DCs involving lymphocyte activation. Control of Mϕ phenotypic balance from proinflammatory M1 to reparative M2 is a goal of investigators to optimize the host response to biomaterials. Similarly, control of DC phenotype from proinflammatory to toleragenic is of interest in vaccine delivery and tissue engineering/transplantation situations, respectively. This review discusses the interconnection between innate and adaptive immunity, the comparative and contrasting phenotypes and roles of Mϕs and DCs in immunity, their responses to biomaterials and the strategies to modulate their phenotype for applications in tissue engineering and vaccine delivery. Furthermore, the collaboration between and unique roles of DCs and Mϕs needs to be addressed in future studies to gain a more complete picture of host responses toward combination products.

Immature dendritic cells (iDCs) were derived from human peripheral blood monocytes, and treated with 75:25 poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) or film to assess the resultant dendritic cell (DC) maturation as compared to positive control of lipopolysaccharide (LPS) treatment for DC maturation or negative control of untreated iDCs. The effect of PLGA contact on DC maturation was examined as one possible explanation for the PLGA adjuvant effect we have observed in the enhancement of an immune response to codelivered model antigen, as adjuvants act through the maturation of DCs. Culturing iDCs with PLGA MPs or PLGA film resulted in morphology similar to that of LPS-matured DCs and the association, or possible internalization, of PLGA MPs. Furthermore, biomaterial-treated iDCs demonstrated an increase in MHC class II and costimulatory molecule expression compared to iDCs but to a lower level than that of LPS-matured DCs. Direct iDC contact with PLGA MPs was necessary for maturation. Immature DCs exposed to PLGA MPs were stimulatory of allogeneic T-cell proliferation, whereas cells exposed to PLGA film were not. Further, PLGA MPs supported a moderate delayed type hypersensitivity reaction in mice indicative of in vivo DC maturation. Taken together, these results suggest that PLGA is a DC maturation stimulus and that the form of the biomaterial may influence the extent of DC maturation.