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.
Sun
Doo-Hoon
DH
Orthopaedic Research Laboratory, Stanford University School of Medicine, Stanford, CA 94305-5341, USA.
Trindade
Michael C D
MC
Nakashima
Yasuharu
Y
Maloney
William J
WJ
Goodman
Stuart B
SB
Schurman
David J
DJ
Smith
R Lane
RL
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