Accumulation of LPS by polyethylene particles decreases bone attachment to implants

Abstract

Molecules absorbed on the surface of particulate wear debris may contribute to inflammatory reactions that lead to aseptic loosening of implants. Lipopolysaccharide (LPS), a bacterial endotoxin, can attach to many biomaterials and stimulate macrophages to secrete osteoclast-activating cytokines. We tested the adsorption of LPS by polyethylene particles in vitro and examined the biological effects of LPS absorption on bone remodeling around implants in vivo. Polyethylene particles were incubated in radiolabeled LPS solutions, and adsorption of LPS by the particles was quantified by radioassay. Because polyethylene particles are hydrophobic and less dense than water, they floated and clumped when incubated in a water solution of LPS, resulting in low adsorption of LPS. However, when particles were incubated in an ethanol solution of LPS, most of the LPS was adsorbed by the particles, and was resistant to washing with water. Triton X-100 (10%), however, effectively washed the LPS off the particles. In a rat model, the presence of polyethylene particles around the implant in the femoral canal decreased bone attachment to the implant at 6 weeks. Incubating the particles with LPS before implantation, or intermittent administration of LPS systemically, further decreased bone-implant attachment to similar extents, but had no effect on the bone density of the control side femurs. Our data indicate that polyethylene particles have high affinity for LPS, depending on many factors, especially the solvents of the LPS. Intermittent systemic administration of LPS affects bone remodeling but only occurs in the area containing polyethylene particles and titanium implants, supporting the hypothesis that the presence of polyethylene particles around implants can result in accumulation of LPS from exogenous sources. This may cause local levels of LPS that are high enough to affect bone remodeling around implants. ß

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

“…This translocation of PAMPs from the gut can be increased by minor surgical procedures, such as colonoscopy, a high-fat diet, or even a single high-fat meal [3,14,52,71,84]. Also consistent with the possibility that circulating PAMPs could traffic to the periprosthetic tissue and induce inflammation locally are the findings that total joint arthroplasty increases circulating LPS levels [113] and that LPS from the circulation accumulates around ''endotoxin-free'' particles after implantation in rodents [104,114]. The local effects of the PAMPs can also include increased corrosion of titanium surfaces, which in turn can increase PAMP binding to the surface [6].…”

Bacterial Pathogen-associated Molecular Patterns Stimulate Biological Activity of Orthopaedic Wear Particles by Activating Cognate Toll-like Receptors

“…For example, the rate of aseptic loosening is reduced by prophylactic antibiotics (12), and we and many other investigators have shown that adherent LPS increases the biological activity of orthopaedic wear particles both in cell culture and in animal models (10). Moreover, detectable levels of LPS exist in peri-prosthetic tissue of a subset of aseptic loosening patients (13), and LPS accumulates in the tissue surrounding implanted wear particles (14,15). We and others have also showed that TLR4, 2 the primary receptor for LPS, contributes to the biological activity of wear particles in both cell culture and murine model systems (16,17).…”

Severe Impingement of Lumbar Disc Replacements Increases the Functional Biological Activity of Polyethylene Wear Debris

“…At present, the biological activity model does not include the contributions of pro-inflammatory factors in vivo (e.g., adsorption of endotoxin/protein [75][76][77][78][79][80] and/or the extent of polyethylene particle oxidation [81][82][83] ), so further investigation of the inflammatory cytokine responses to wear debris in the spine is warranted. Nevertheless, these results lend support to the use of biological activity calculations in combination with particle size and number in individual size ranges to illustrate differences in total disc replacement wear modes.…”