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When non-biological (e.g., synthetic) materials are implanted into higher organisms, they elicit a foreign body response (FBR) that begins with non-specific protein adsorption, followed by inflammation, and eventual resolution with the formation of an avascular fibrous capsule that walls off the implant from the surrounding tissue. Despite extensive studies describing the FBR, the molecular and cellular mechanisms that lead to the FBR are not well understood. Our group utilizes transgenic mouse models to study pathways and innate immune cells to identify those that are responsible for the FBR. In the context of tissue engineering when cells are present within a scaffold, the severity of the FBR can negatively impact cells and their ability to produce new tissue. Our group is working to identify pathways that lead to the FBR and to use this knowledge to develop new materials that attenuate the FBR. More recently, we have extended our studies to microparticles as a potential delivery vehicle to target immune cells. Our overarching goal is to develop biomaterials, which when placed in vivo, attenuates inflammation, facilitates host tissue remodeling at the material-tissue interface, and promotes functional integration of the device and tissue engineering scaffold.