Inflammatory responses to orthopaedic biomaterials in the murine air pouch

Wooley, Paul H.; Morren, Robert; Andary, John; Sud, Sudha; Yang, Shang-You; Mayton, Lois; Markel, David C.; Sieving, Allison; Nasser, Sam

doi:10.1016/s0142-9612(01)00134-x

Cited by 189 publications

(189 citation statements)

References 26 publications

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“…The size and distribution of UHMWPE particles was evaluated using a Coulter particle counter and by scanning electron microscopy, as described elsewhere. 21 The UHMWPE particles had a mean particle diameter of 2.6 mm, with a range from <0.6 mm to 21 mm. The particles were washed in 70% ethanol solution to remove endotoxin and heat sterilized, and the absence of endotoxin was confirmed using the Limulus assay (Endosafe; Charles Rivers, Charlestown, SC).…”

Section: Methodsmentioning

confidence: 98%

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

Ren

Peng

et al. 2006

Journal Orthopaedic Research

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Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK À/À ) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK À/À mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK þ/þ ) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK À/À mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1b, TNFa, and RANKL. However, the UHMWPE-induced inflammation in RANK À/À mice was not associated with the osteoclastic bone resorption observed in RANK þ/þ mice. In RANK þ/þ mice subjected to UHMWPE stimulation, a large number of TRAP þ cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP þ cells were found in UHMWPE-containing pouch tissues of RANK À/À mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK À/À mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (mCT)] of implanted bone was observed in RANK À/À mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK À/À mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response. ß

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Section: Methodsmentioning

confidence: 98%

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

Ren

Peng

et al. 2006

Journal Orthopaedic Research

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“…Evidence in support of this includes the observations that osteolysis is correlated with higher wear rates [2] and that vast numbers of wear particles are found associated with the periprosthetic interfacial membrane removed during revision surgery [3][4][5]. Furthermore, experimental systems have demonstrated that particulate debris can induce osteolysis in a variety of animal models [6][7][8][9][10][11][12], and inflammatory responses in cultured macrophages [8,[13][14][15][16][17]. Taken together, and notwithstanding evidence for some involvement of other factors-such as fluid pressure [18] and adherent endotoxin [19], which lie beyond the scope of this review-these findings clearly demonstrate that wear debris represents the single most important underlying cause of periprosthetic osteolysis.…”

Section: Introductionmentioning

confidence: 91%

The Central Role of Wear Debris in Periprosthetic Osteolysis

et al. 2006

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Periprosthetic osteolysis remains the leading complication of total hip arthroplasty, often resulting in aseptic loosening of the implant, and a requirement for revision surgery. Wear-generated particular debris is the main cause of initiating this destructive process. The purpose of this article is to review recent advances in our understanding of how wear debris causes osteolysis, and emergent strategies for the avoidance and treatment of this disease. The most important cellular target for wear debris is the macrophage, which responds to particle challenge in two distinct ways, both of which contribute to increased bone resorption. First, it is well known that wear debris activates proinflammatory signaling, which leads to increased osteoclast recruitment and activation. More recently, it has been established that wear also inhibits the protective actions of antiosteoclastogenic cytokines such as interferon gamma, thus promoting differentiation of macrophages to bone-resorbing osteoclasts. Osteoblasts, fibroblasts, and possibly lymphocytes may also be involved in responses to wear. At a molecular level, wear particles activate MAP kinase cascades, NF.B and other transcription factors, and induce expression of suppressors of cytokine signaling. Strategies to reduce osteolysis by choosing bearing surface materials with reduced wear properties (such as metal-on-metal) should be balanced by awareness that reducing particle size may increase biological activity. Finally, although therapeutic agents against proinflammatory mediators [such as tumor necrosis factor (TNF)] and osteoclasts (bisphosphonates and molecules blocking RANKL signaling) have shown promise in animal models, no approved treatments are yet available to osteolysis patients. Considerable efforts are underway to develop such therapies, and to identify novel targets for therapeutic intervention.

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“…The findings are strongly supportive of the concept of local tissue haptenization resulting in an organized accumulation of sensitized lymphocytes, notably both T and B cells. Animal models of metal debris in inflammatory tissues [3,77] have demonstrated elevated macrophage accumulation and the induction of inflammatory cytokines and chemokines with a major elicitation of interleukin-1b the predominant inflammatory feature and expression of CCL2 corresponding with macrophage recruitment. The air pouch model consistently responds with increased cellularity in response to Co-Cr debris, although the response is not elevated over reactions to conventional UHMWPE.…”

Section: Search Strategy and Criteriamentioning

confidence: 99%

How Has the Introduction of New Bearing Surfaces Altered the Biological Reactions to Byproducts of Wear and Modularity?

Wooley

2014

Clin Orthop Relat Res

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Background Biological responses to wear debris were largely elucidated in studies focused on conventional ultrahigh-molecular-weight polyethylene (UHMWPE) and some investigations of polymethymethacrylate cement and orthopaedic metals. However, newer bearing couples, in particular metal-on-metal but also ceramic-on-ceramic bearings, may induce different biological reactions. Questions/purposes Does wear debris from the newer bearing surfaces result in different biological responses compared with the known responses observed with conventional metal-on-UHMWPE bearings?Methods A Medline search of articles published after 1996 supplemented by a hand search of reference lists of included studies and relevant conference proceedings was conducted to identify the biological responses to orthopaedic wear debris with a focus on biological responses to wear generated from metal-on-highly crosslinked polyethylene, metal-on-metal, ceramic-on-ceramic, and ceramicon-polyethylene bearings. Articles were selected using criteria designed to identify reports of wear debris particles and biological responses contributing to prosthesis failure. Case reports and articles focused on either clinical outcomes or tribology were excluded. A total of 83 papers met the criteria and were reviewed in detail.

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Inflammatory responses to orthopaedic biomaterials in the murine air pouch

Cited by 189 publications

References 26 publications

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

The Central Role of Wear Debris in Periprosthetic Osteolysis

How Has the Introduction of New Bearing Surfaces Altered the Biological Reactions to Byproducts of Wear and Modularity?

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Inflammatory responses to orthopaedic biomaterials in the murine air pouch

Cited by 189 publications

References 26 publications

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK–/– mice

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK–/– mice

The Central Role of Wear Debris in Periprosthetic Osteolysis

How Has the Introduction of New Bearing Surfaces Altered the Biological Reactions to Byproducts of Wear and Modularity?

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Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice