Adherent Lipopolysaccharide Inhibits Osseointegration In Vivo

INTRODUCTION: Osseointegration is crucial for early fixation as well as long-term success of orthopaedic implants. Contaminants, such as bacterial debris and manufacturing residues, can remain on an implant surface after sterilization procedures and inhibit osseointegration [1]. Bacterial debris contains pathogen associated molecular patterns (PAMPs), which are molecular motifs that activate the immune system. The best characterized PAMP, LPS, is derived from Gram-negative bacteria, is ubiquitous, has a high affinity for biomaterial surfaces, and is resistant to removal by sterilization or passivation [2,3]. FDA guidelines require LPS testing by immersing medical devices in water and then measuring the eluted LPS. However, water elution of LPS is inefficient [2,3]. Considerable amounts of LPS may therefore adhere to the surface of an implant despite low levels in the eluate. For example, adherent LPS exists on implant surfaces sterilized and packaged by an orthopaedic implant manufacturer [3]. Both soluble LPS [4,5,6] and LPS adherent to implant material [7] inhibit osteoblast differentiation in cell culture. We therefore hypothesized that adherent LPS on the surface of implants can inhibit osseointegration in vivo.