Staphylococcus aureus is responsible for approximately 80% of all cases of human osteomyelitis. RANK-L is an essential signal produced by osteoblasts and is required for full osteoclastic differentiation. PGE₂ - induced bone resorption involves both inducible cyclooxygenase (COX-2), as well as RANK-L. Our studies show that during infection with S. aureus, osteoblasts increase RANK-L and PGE₂ secretion. Through the use of NS-398, a specific COX-2 inhibitor, we show that when PGE₂ production is inhibited, RANK-L production is decreased. In the current study, we also demonstrate that effective killing of intracellular S. aureus is possible by treating the infected osteoblasts with nanoparticles loaded with nafcillin antibiotic. While titanium alloys are the preferred material of choice for orthopaedic implants, they do not mediate osseointegration (intimate apposition of bone to the implant surface). Enhancement of titanium (Ti) based biomaterials is therefore necessary to increase the functional lifespan of an implant. S. aureus can bind to biomaterials directly and also attach efficiently to osteoblasts. Moreover, as UV-killed S. aureus does not stimulate immune modulator expression, we investigated whether UV-killed bacteria could serve as a novel osteoconductive coating on Ti alloy surfaces. Our in vitro data demonstrate that osteoblast adhesion and matrix synthesis was enhanced on Ti surfaces coated with bacteria compared to uncoated surfaces. In vivo, the osteoconductivity of S. aureus-coated implants was increased at 8 weeks compared to the uncoated implants.