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

doi:10.1007/s11095-014-1310-x

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 journal › Article › peer-review

7 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2086-2094
Number of pages	9
Journal	Pharmaceutical Research
Volume	31
Issue number	8
DOIs	https://doi.org/10.1007/s11095-014-1310-x
State	Published - Aug 2014

Keywords

ELVIS
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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10.1007/s11095-014-1310-x

Cite this

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title = "Early diagnosis of orthopedic implant failure using macromolecular imaging agents",

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.",

keywords = "ELVIS, HPMA copolymer, aseptic implant loosening, early diagnosis, inflammation targeting",

author = "Ke Ren and Anand Dusad and Yijia Zhang and Purdue, {P. Edward} and Fehringer, {Edward V.} and Garvin, {Kevin L.} and Goldring, {Steven R.} and Dong Wang",

note = "Funding Information: This study was supported in part by NIH/NIAMS R01 AR053325 and R01 AR062680 to D.W. and an ACR-REF: Within Our Reach Grant to S.R.G. The authors would like to thank Ms. Laura Weber for proof-reading the manuscript. Publisher Copyright: {\textcopyright} 2014 Springer Science+Business Media New York.",

year = "2014",

month = aug,

doi = "10.1007/s11095-014-1310-x",

language = "English (US)",

volume = "31",

pages = "2086--2094",

journal = "Pharmaceutical Research",

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number = "8",

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TY - JOUR

T1 - Early diagnosis of orthopedic implant failure using macromolecular imaging agents

AU - Ren, Ke

AU - Dusad, Anand

AU - Zhang, Yijia

AU - Purdue, P. Edward

AU - Fehringer, Edward V.

AU - Garvin, Kevin L.

AU - Goldring, Steven R.

AU - Wang, Dong

N1 - Funding Information: This study was supported in part by NIH/NIAMS R01 AR053325 and R01 AR062680 to D.W. and an ACR-REF: Within Our Reach Grant to S.R.G. The authors would like to thank Ms. Laura Weber for proof-reading the manuscript. Publisher Copyright: © 2014 Springer Science+Business Media New York.

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

KW - ELVIS

KW - HPMA copolymer

KW - aseptic implant loosening

KW - early diagnosis

KW - inflammation targeting

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JO - Pharmaceutical Research

JF - Pharmaceutical Research

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ER -

Early diagnosis of orthopedic implant failure using macromolecular imaging agents

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