Early detection and treatment of wear particle-induced inflammation and bone loss in a mouse calvarial osteolysis model using HPMA copolymer conjugates

Ke Ren, P. Edward Purdue, Lyndsey Burton, Ling Dong Quan, Edward V. Fehringer, Geoffrey Milton Thiele, Steven R. Goldring, Dong Wang

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Wear particle-induced inflammation is considered to be the major cause of aseptic implant loosening and clinical failure after total joint replacement. Due to the frequent absence of symptoms, early detection and intervention prior to implant failure presents a significant challenge. To address this issue, a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based optical imaging contrast agent (P-IRDye) was developed and used for the detection of wear particle-induced inflammation employing a murine calvaria osteolysis model. The particle-induced osteolysis of calvaria was evaluated by H&E, tartrate-resistant acid phosphatase (TRAP) staining and μ-CT after necropsy. One-day post particle implantation, P-IRDye was administrated to the mice via tail vein injection. Live imaging of the animals 6 days after implantation revealed the preferential distribution and sustained retention of the macromolecular contrast agent at the site of particle implantation. Immunohistochemical staining and FACS analyses of the calvaria-associated soft tissue revealed extensive uptake of the HPMA copolymer by F4/80, Ly-6G (Gr1) and CD11c positive cells, which accounts for the retention of the macromolecular probes at the inflammatory sites. To test the potential of the system for therapeutic intervention, an acid-labile HPMA copolymer-dexamethasone conjugate (P-Dex) was prepared and shown to prevent the particle-induced inflammation and bone damage in the calvaria osteolysis model.

Original languageEnglish (US)
Pages (from-to)1043-1051
Number of pages9
JournalMolecular Pharmaceutics
Volume8
Issue number4
DOIs
StatePublished - Aug 1 2011

Fingerprint

Osteitis
Osteolysis
Skull
Contrast Media
Replacement Arthroplasties
Staining and Labeling
Inflammation
Optical Imaging
Therapeutics
Dexamethasone
Tail
Veins
Injections
Acids
N-(2-hydroxypropyl)methacrylamide

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Early detection and treatment of wear particle-induced inflammation and bone loss in a mouse calvarial osteolysis model using HPMA copolymer conjugates. / Ren, Ke; Purdue, P. Edward; Burton, Lyndsey; Quan, Ling Dong; Fehringer, Edward V.; Thiele, Geoffrey Milton; Goldring, Steven R.; Wang, Dong.

In: Molecular Pharmaceutics, Vol. 8, No. 4, 01.08.2011, p. 1043-1051.

Research output: Contribution to journalArticle

Ren, Ke ; Purdue, P. Edward ; Burton, Lyndsey ; Quan, Ling Dong ; Fehringer, Edward V. ; Thiele, Geoffrey Milton ; Goldring, Steven R. ; Wang, Dong. / Early detection and treatment of wear particle-induced inflammation and bone loss in a mouse calvarial osteolysis model using HPMA copolymer conjugates. In: Molecular Pharmaceutics. 2011 ; Vol. 8, No. 4. pp. 1043-1051.
@article{f578824d4cf04438b4d26c3c9c54a12f,
title = "Early detection and treatment of wear particle-induced inflammation and bone loss in a mouse calvarial osteolysis model using HPMA copolymer conjugates",
abstract = "Wear particle-induced inflammation is considered to be the major cause of aseptic implant loosening and clinical failure after total joint replacement. Due to the frequent absence of symptoms, early detection and intervention prior to implant failure presents a significant challenge. To address this issue, a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based optical imaging contrast agent (P-IRDye) was developed and used for the detection of wear particle-induced inflammation employing a murine calvaria osteolysis model. The particle-induced osteolysis of calvaria was evaluated by H&E, tartrate-resistant acid phosphatase (TRAP) staining and μ-CT after necropsy. One-day post particle implantation, P-IRDye was administrated to the mice via tail vein injection. Live imaging of the animals 6 days after implantation revealed the preferential distribution and sustained retention of the macromolecular contrast agent at the site of particle implantation. Immunohistochemical staining and FACS analyses of the calvaria-associated soft tissue revealed extensive uptake of the HPMA copolymer by F4/80, Ly-6G (Gr1) and CD11c positive cells, which accounts for the retention of the macromolecular probes at the inflammatory sites. To test the potential of the system for therapeutic intervention, an acid-labile HPMA copolymer-dexamethasone conjugate (P-Dex) was prepared and shown to prevent the particle-induced inflammation and bone damage in the calvaria osteolysis model.",
author = "Ke Ren and Purdue, {P. Edward} and Lyndsey Burton and Quan, {Ling Dong} and Fehringer, {Edward V.} and Thiele, {Geoffrey Milton} and Goldring, {Steven R.} and Dong Wang",
year = "2011",
month = "8",
day = "1",
doi = "10.1021/mp2000555",
language = "English (US)",
volume = "8",
pages = "1043--1051",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - Early detection and treatment of wear particle-induced inflammation and bone loss in a mouse calvarial osteolysis model using HPMA copolymer conjugates

AU - Ren, Ke

AU - Purdue, P. Edward

AU - Burton, Lyndsey

AU - Quan, Ling Dong

AU - Fehringer, Edward V.

AU - Thiele, Geoffrey Milton

AU - Goldring, Steven R.

AU - Wang, Dong

PY - 2011/8/1

Y1 - 2011/8/1

N2 - Wear particle-induced inflammation is considered to be the major cause of aseptic implant loosening and clinical failure after total joint replacement. Due to the frequent absence of symptoms, early detection and intervention prior to implant failure presents a significant challenge. To address this issue, a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based optical imaging contrast agent (P-IRDye) was developed and used for the detection of wear particle-induced inflammation employing a murine calvaria osteolysis model. The particle-induced osteolysis of calvaria was evaluated by H&E, tartrate-resistant acid phosphatase (TRAP) staining and μ-CT after necropsy. One-day post particle implantation, P-IRDye was administrated to the mice via tail vein injection. Live imaging of the animals 6 days after implantation revealed the preferential distribution and sustained retention of the macromolecular contrast agent at the site of particle implantation. Immunohistochemical staining and FACS analyses of the calvaria-associated soft tissue revealed extensive uptake of the HPMA copolymer by F4/80, Ly-6G (Gr1) and CD11c positive cells, which accounts for the retention of the macromolecular probes at the inflammatory sites. To test the potential of the system for therapeutic intervention, an acid-labile HPMA copolymer-dexamethasone conjugate (P-Dex) was prepared and shown to prevent the particle-induced inflammation and bone damage in the calvaria osteolysis model.

AB - Wear particle-induced inflammation is considered to be the major cause of aseptic implant loosening and clinical failure after total joint replacement. Due to the frequent absence of symptoms, early detection and intervention prior to implant failure presents a significant challenge. To address this issue, a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based optical imaging contrast agent (P-IRDye) was developed and used for the detection of wear particle-induced inflammation employing a murine calvaria osteolysis model. The particle-induced osteolysis of calvaria was evaluated by H&E, tartrate-resistant acid phosphatase (TRAP) staining and μ-CT after necropsy. One-day post particle implantation, P-IRDye was administrated to the mice via tail vein injection. Live imaging of the animals 6 days after implantation revealed the preferential distribution and sustained retention of the macromolecular contrast agent at the site of particle implantation. Immunohistochemical staining and FACS analyses of the calvaria-associated soft tissue revealed extensive uptake of the HPMA copolymer by F4/80, Ly-6G (Gr1) and CD11c positive cells, which accounts for the retention of the macromolecular probes at the inflammatory sites. To test the potential of the system for therapeutic intervention, an acid-labile HPMA copolymer-dexamethasone conjugate (P-Dex) was prepared and shown to prevent the particle-induced inflammation and bone damage in the calvaria osteolysis model.

UR - http://www.scopus.com/inward/record.url?scp=79961048961&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961048961&partnerID=8YFLogxK

U2 - 10.1021/mp2000555

DO - 10.1021/mp2000555

M3 - Article

C2 - 21438611

AN - SCOPUS:79961048961

VL - 8

SP - 1043

EP - 1051

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 4

ER -