title: Early diagnosis of orthopedic implant failure using macromolecular imaging agents.
abstract: OBJECTIVE
  To develop and evaluate diagnostic tools for early detection of wear particle-induced orthopaedic implant loosening.
  
  
  METHODS
  N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer was tagged with a near infrared dye and used to detect the inflammation induced by polymethylmethacrylate (PMMA) particles in a murine peri-implant osteolysis model. It was established by inserting an implant into the distal femur and challenging with routine PMMA particles infusion. The osteolysis was evaluated by micro-CT and histological analysis at different time points.
  
  
  RESULTS
  Significant peri-implant osteolysis was found 3-month post PMMA particle challenge by micro-CT and histological analysis. At 1-month post challenge, when there was no significant peri-implant bone loss, the HPMA copolymer-near infrared dye conjugate was found to specifically target the femur with PMMA particles deposition, but not the contralateral control femur with phosphate buffered saline (PBS) infusion.
  
  
  CONCLUSIONS
  The results from this study demonstrate the feasibility of utilizing the macromolecular diagnostic agent to detect particle-induced peri-implant inflammation prior to the development of detectable osteolysis. Recognition of this early pathological event would provide the window of opportunity for prevention of peri-implant osteolysis and subsequent orthopaedic implant failure.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, COP 3026, Omaha, NE, 68198-6025, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Anand
authors.initials: A
authors.lastname: Dusad
authors.forename: Yijia
authors.initials: Y
authors.lastname: Zhang
authors.forename: P Edward
authors.initials: PE
authors.lastname: Purdue
authors.forename: Edward V
authors.initials: EV
authors.lastname: Fehringer
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Garvin
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldring
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D042241:Early Diagnosis; D005269:Femur / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000601:surgery*; D019793:Fluorescein; D046911:Macromolecular Substances; D008297:Male; D008689:Methacrylates; D051379:Mice; D019904:Polymethyl Methacrylate / Q000633:toxicity; D019736:Prostheses and Implants / Q000009:adverse effects*; D011475:Prosthesis Failure; D014057:Tomography, X-Ray Computed
chemical_list: D046911:Macromolecular Substances; D008689:Methacrylates; D019904:Polymethyl Methacrylate; D019793:Fluorescein; C032802:hydroxypropyl methacrylate