title: Macrophage reactivity to different polymers demonstrates particle size- and material-specific reactivity: PEEK-OPTIMA(®) particles versus UHMWPE particles in the submicron, micron, and 10 micron size ranges.
abstract: Biologic reactivity to orthopedic implant debris is generally the main determinant of long-term clinical performance where released polymeric particles of Ultra-high molecular weight polyethylene (UHMWPE) remain the most prevalent debris generated from metal-on-polymer bearing total joint arthroplasties. Polymeric alternatives to UHMWPE such as polyetherether-ketone (PEEK) may have increased wear resistance but the bioreactivity of PEEK-OPTIMA particles on peri-implant inflammation remains largely uncharacterized. We evaluated human monocyte/macrophage responses (THP-1s and primary human) when challenged by PEEK-OPTIMA, UHMWPE, and X-UHMWPE particles of three particle sizes (0.7 um, 2 um, and 10 um) at a dose of 20 particles-per-cell at 24- and 48-h time points. Macrophage responses were measured using cytotoxicity assays, viability assays, proliferation assays and cytokine analysis (IL-1b, IL-6, IL-8, MCP-1, and TNF-α). In general, there were no significant differences between PEEK-OPTIMA, UHMWPE, and X-UHMWPE particles on macrophage viability or proliferation. However, macrophages demonstrated greater cytotoxicity responses to UHMWPE and X-UHMWPE than to PEEK-OPTIMA at 24 and 48 h, where 0.7 μm-UHMWPE particles produced the highest amount of cytotoxicity. Particles of X-UHMWPE more than PEEK-OPTIMA and UHMWPE induced IL-1β, IL-6, MCP-1, and TNF-α at 24 h, p < 0.05 (no significant differences at 48 h). On average, cytokine production was more adversely affected by larger 10 μm particles than by 0.7 and 2 μm sized particles. While limitations of in vitro analysis apply to this study, PEEK-OPTIMA particles were more biocompatible than UHMWPE particles, in that they induced less inflammatory cytokine responses and thus, in part, demonstrates that PEEK-OPTIMA implant debris does not represent an increased inflammatory risk over that of UHMWPE.
authors.affiliation: Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois 60612; BioEngineering Solutions Inc., Oak Park, Illinois 60304. nhallab@rush.edu.
authors.forename: Nadim James
authors.initials: NJ
authors.lastname: Hallab
authors.forename: Kyron
authors.initials: K
authors.lastname: McAllister
authors.forename: Mark
authors.initials: M
authors.lastname: Brady
authors.forename: Marcus
authors.initials: M
authors.lastname: Jarman-Smith
mesh_terms: D019643:Arthroplasty, Replacement; D001577:Benzophenones; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011095:Polyethylenes / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers
chemical_list: D001577:Benzophenones; D020099:Coated Materials, Biocompatible; D016207:Cytokines; D007659:Ketones; D011095:Polyethylenes; D011108:Polymers; C111601:ultra-high molecular weight polyethylene; C063834:polyetheretherketone; D011092:Polyethylene Glycols