Murine model of prosthesis failure for the long‐term study of aseptic loosening

Abstract

We examined a novel mouse model of wear debris-induced prosthesis instability and osteolysis, and its application for the evaluation of therapy. A stainless steel or titanium-alloy pin was implanted into the proximal tibia to form a contiguous surface with the articular cartilage. In some mice, titanium particles were injected into the tibial canal during the surgery, followed by monthly intraarticular injection. MicroCT scans revealed that the implants without particle challenge were stable without bone mineral density changes for 6 months. Histological analysis showed new bone formation around the implant at 6 weeks postsurgery. Periprosthetic soft tissue with inflammatory cells was a ubiquitous finding at the interface between the implant and surrounding bone in samples exposed to titanium particles, and expression of IL-1b, TNFa, and CD68 was common in these joints. Pullout tests indicated that an average 5N load was required to pull out stable implants from surrounding bone. However, particle stimulation dramatically reduced the pullout force to less than 0.4 N. The feasibility of in vivo gene transfer on this model was confirmed by X-gal staining of synovial membrane and periprosthetic tissue after injection of AAV-LacZ in the prosthetic joint. This murine model of weight-bearing knee prosthesis provides an economical, reproducible, and easily obtained means to study joint arthroplasty failure. The ability to evaluate the biomechanical properties of the prosthetic joint, in addition to histological and biochemical examination, results in a useful model to investigate many of the properties of prosthetic joint components during the response to debris-associated osteolysis. ß

Interleukin-1 Receptor-associated Kinase-4 (IRAK4) Promotes Inflammatory Osteolysis by Activating Osteoclasts and Inhibiting Formation of Foreign Body Giant Cells

“…Recently, studies of tissues harvested from revised joint replacements reported that proinflammatory M1 factors were predominant over M2 anti-inflammatory molecules (51)(52)(53)(54). Moreover, Rao et al (55) reported that IL-4, an M2 macrophage activator, mitigated polyethylene particle-induced osteolysis through macrophage polarization.…”

New animal models of wear-particle osteolysis

“…However, this can be judged as a preliminary study, as no bone loss has been quantitatively proved (polystyrene particles used), only a few animals were included, the exact number of particles delivered could only be grossly extrapolated, and-surprisingly-no particles were observed on any histological bone section. We consider that major improvements were provided by Yang et al [48] and Zhang et al [49]. These authors used an effective long-term implant (pin implanted into proximal tibia to form a contiguous surface with the articular cartilage); an implant that stays well fixed after six months without particle challenge; monthly intra-articular injections for six months to achieve a long-term course (chronic reaction); pull-out tests as additional outcome measure; and most of all, in vivo gene transfer (using adenoassociated virus) to improve the delivery system of OPG-related therapy.…”

Review of periprosthetic osteolysis in total joint arthroplasty: An emphasis on host factors and future directions

“…This occurs largely due to the release of pro-inflammatory immune modulators such as IL-1a and b, IL-6, IL-18, and TNFa. [8][9][10][11][12][13][14] The NOD-like receptor protein, NALP3, located in the cytosol of macrophages, initiates the cleavage of pro-IL-1b into its mature, secreted form, IL-1b effectively triggering IL-1-associated inflammatory cascades. 13 Once these microdebris wear particles are phagocytized by macrophages, they release the above mentioned cytokines to attract and recruit more phagocytes that will release more chemotaxins which, in turn, perpetuates a positive feedback cycle of inflammation activation.…”

“…As has been demonstrated in the literature, IL-1b has been intimately linked to osteolysis; to the extent of being used a secondary measure of periprosthetic bone resorption in several studies. [8][9][10][11][12][13][14][15]17,57,74,75 The activation of cytokine released by uric acid crystals in gout is similar to wear-debris particles activation an immune response in the setting of aseptic loosening, and therefore lies the potential benefit of these pharmacologics in periprosthetic osteolysis. A recent study has also REVIEW OF PERIPROSTHETIC OSTEOLYSIS proposed that the prophylactic administration of erythromycin may maximize the longevity of a prosthetic joint by lessening, or at least delaying, the effects of osteolysis immediately adjacent to the implanted construct.…”