Early Diagnosis of Orthopedic Implant Failure Using Macromolecular Imaging Agents

• Published in: Pharmaceutical research Vol. 31; no. 8; pp. 2086 - 2094
• Main Authors: Ren, Ke, Dusad, Anand, Zhang, Yijia, Purdue, P. Edward, Fehringer, Edward V., Garvin, Kevin L., Goldring, Steven R., Wang, Dong
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.08.2014; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Dyes; Early Diagnosis; Failure; Femur - diagnostic imaging; Femur - drug effects; Femur - surgery; Fluorescein; Macromolecular Substances; Male; Medical diagnosis; Medical imaging; Medical Law; Methacrylates; Mice; Orthopedics; Pharmaceutical sciences; Pharmacology/Toxicology; Pharmacy; Polymethyl Methacrylate - toxicity; Prostheses and Implants - adverse effects; Prosthesis Failure; Research Paper; Rodents; Tomography, X-Ray Computed; Transplants & implants; early diagnosis; ELVIS; inflammation targeting; aseptic implant loosening; HPMA copolymer
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-014-1310-x

ABSTRACT 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.