title: Inflammatory responses to orthopaedic biomaterials in the murine air pouch.
abstract: An in vivo model of the inflammatory response to orthopaedic biomaterials was used to examine cellular and cytokine responses to polymer particles of ultra high molecular weight polyethylene (UHMWPE) and polymethylmethacrylate (PMMA), and metal particles of cobalt-chrome (Co-Cr) and titanium alloy (Ti-6Al-4V). Responses were determined separately and in combinations, to examine interactions between different forms of biomaterials. Murine air pouches were injected with particle suspensions, and reactions evaluated using histological, immunological, and molecular techniques. All particulate biomaterials caused significant increases in membrane thickness compared with control (saline) air pouches, with the highest reaction seen in response to Ti-6Al-4V particles. A synergistic increase in membrane thickness was observed when PMMA was combined with UHMWPE, suggesting that multiple biomaterial stimuli markedly increase the inflammatory reaction. Cellular analysis indicated that all particles increased the absolute number and the percentage of macrophages in the membrane over the control level, with the most pronounced increase due to individual biomaterial occurring with UHMWPE particles. Cytokine analysis revealed that biomaterials provoked a strong IL-1 response. Ti-6Al-4V stimulated the highest IL-6 gene transcription and the lowest IL-1 gene transcription. The data suggest that synergism in the inflammatory response to biomaterials may be important in adverse responses to orthopaedic wear debris.
authors.affiliation: Department of Orthopaedic Surgery, Wayne State University School of Medicine, Hutzel Hospital, Detroit, MI 48201, USA. ad8754@wayne.edu
authors.forename: Paul H
authors.initials: PH
authors.lastname: Wooley
authors.forename: Robert
authors.initials: R
authors.lastname: Morren
authors.forename: John
authors.initials: J
authors.lastname: Andary
authors.forename: Sudha
authors.initials: S
authors.lastname: Sud
authors.forename: Shang-You
authors.initials: SY
authors.lastname: Yang
authors.forename: Lois
authors.initials: L
authors.lastname: Mayton
authors.forename: David
authors.initials: D
authors.lastname: Markel
authors.forename: Allison
authors.initials: A
authors.lastname: Sieving
authors.forename: Sam
authors.initials: S
authors.lastname: Nasser
mesh_terms: D000497:Alloys; D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D002858:Chromium Alloys / Q000009:adverse effects*; D005260:Female; D007249:Inflammation / Q000139:chemically induced*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D011095:Polyethylenes / Q000009:adverse effects*; D019904:Polymethyl Methacrylate / Q000009:adverse effects*; D014025:Titanium / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000497:Alloys; D001672:Biocompatible Materials; D002858:Chromium Alloys; D007375:Interleukin-1; D011095:Polyethylenes; D014409:Tumor Necrosis Factor-alpha; C111601:ultra-high molecular weight polyethylene; C031462:titanium alloy (TiAl6V4); D019904:Polymethyl Methacrylate; D014025:Titanium