Human serum opsonization of orthopedic biomaterial particles: protein-binding and monocyte/macrophage activation in vitro.
Wear particles generated after total joint arthroplasty activate monocyte/macrophages and incite formation of a granulomatous periprosthetic tissue associated with bone loss and implant loosening. This study tested the hypothesis that selective opsonization of orthopedic implant biomaterial wear particles by human serum proteins influences monocyte/macrophage activation. Serum protein binding to metallic, polymeric, and ceramic particles was determined by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Individual proteins bound to particles were subsequently identified using two-dimensional SDS-PAGE, microsequencing techniques, and SWISS-PROT analysis. Effects of selective protein opsonization on particle-induced monocyte/macrophage activation were assessed by quantification of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha release. Results from one-dimensional gel analyses revealed distinct serum protein-binding patterns specific for each material tested. Two-dimensional gel analysis together with amino acid sequencing of the prominent protein species confirmed the presence of albumin and alpha-1-antitrypsin bound to all particles tested. In contrast to the metallic particles, apolipoprotein was a major species associated with polymeric particles. Opsonization of PMMA particles with purified preparations of each of the identified proteins showed that albumin significantly enhanced particle-induced monocyte/macrophage activation. These data confirm orthopedic biomaterial specific binding of human serum proteins and demonstrate that albumin exacerbates particle-induced monocyte/macrophage activation. Alterations in the chemical and surface properties of orthopedic biomaterials to modulate protein interactions may improve implant longevity.
Orthopaedic Research Laboratory, Stanford University School of Medicine, Stanford, CA 94305-5341, USA.
Doo-Hoon
DH
Sun
Michael C D
MC
Trindade
Yasuharu
Y
Nakashima
William J
WJ
Maloney
Stuart B
SB
Goodman
David J
DJ
Schurman
R Lane
RL
Smith
D001672:Biocompatible Materials / Q000737:chemistry*; D001790:Blood Physiological Phenomena; D001798:Blood Proteins / Q000737:chemistry* / Q000302:isolation & purification; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D008422:Materials Testing; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D009983:Orthopedic Equipment; D019637:Orthopedic Procedures; D011485:Protein Binding
D001672:Biocompatible Materials; D001798:Blood Proteins