Early diagnosis of orthopedic implant failure using macromolecular imaging agents

Ke Ren, Anand Dusad, Yijia Zhang, P. Edward Purdue, Edward V. Fehringer, Kevin L. Garvin, Steven R. Goldring, Dong Wang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Purpose: 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.

Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)2086-2094
Number of pages9
JournalPharmaceutical Research
Issue number8
StatePublished - Aug 2014


  • HPMA copolymer
  • aseptic implant loosening
  • early diagnosis
  • inflammation targeting

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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