Sequence of pathogenesis in osteomyelitis. Top left, Initial trauma produces soft-tissue destruction, bone fragmentation, and contamination by bacteria. In closed wounds, contamination may occur by hematogenous seeding. Top right, As infection progresses, bacterial colonization occurs within protective exopolysaccharide biofilm, which is especially abundant on devitalized bone fragment, which acts as passive substratum for colonization. Bottom left, Host defenses are mobilized against infection but cannot penetrate biofilm. Bottom right, Progressive inflammation and abscess formation result in development of sinus track and in some cases ultimate extrusion of sequestrum, which is focus of resistant infection.