Macrophage and dendritic cell phenotypic diversity in the context of biomaterials

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.