The foreign body response to biomaterial implants has been a major challenge in translating many medical devices into the clinic. The presence of inflammatory cells around the implanted device prevents its functional interaction with the surrounding tissue, and although some inflammation may be desirable to mediate the healing process, a persistent inflammatory response will eventually lead to device failure. Significant efforts to reduce foreign body response have been largely focused on developing hydrophilic and anti-fouling coating materials, however, simply preventing protein adsorption and immune cell adhesion has only had moderate success at reducing inflammation in vivo. In this thesis, we describe a novel approach to mitigate the foreign body response, whereby materials are designed to mimic host tissue by displaying endogenously expressed immunomodulatory molecules that interact with specific inhibitory receptors expressed on immune cells. More specifically, biomaterial surfaces are coated with the recombinantly produced immunomodulatory molecule, CD200, which interacts with the inhibitory receptor CD200R on myeloid cells, preventing material-induced host response by suppressing activation of infiltrated myeloid cells. In Chapter One, a brief introduction and background information is presented, followed by a description of the production and purification of recombinant CD200 protein from both mammalian cells and bacterial cells in Chapter Two. In Chapter Three, we examine whether immobilization of CD200 onto polystyrene surfaces influences on suppressing the activation of macrophages. We found that CD200 indeed suppresses the release of inflammatory mediators secreted by macrophage cells in vitro, and elicited less inflammation in vivo when compared to uncoated materials after subcutaneous implantation. In Chapter Four, we examine whether CD200 influences tissue regeneration after spinal cord injury. CD200-embedded fibrin gel was implanted to spinal cord injured mice, and the effect of CD200 on inflammation and regenerative process was examined. Lastly, Chapter Five concludes the work performed in this Ph.D. study and presents future directions. This work suggests that coating of endogenously expressed immunomodulatory proteins can be used as a strategy to reduce inflammatory response to biomaterials and may potentially be generalized to implants throughout the body.