ADSORPTION OF COLLAGENASE TO PARTICULATE TITANIUM - A POSSIBLE MECHANISM FOR COLLAGENASE LOCALIZATION IN PERIPROSTHETIC TISSUE

Osteolysis is a central feature of aseptic loosening of orthopaedic jo int prostheses. This destructive process is believed to result from ph agocytosis of implant wear debris by periprosthetic and synovial macro phages and the subsequent release of proinflammatory mediators, includ ing collagenase. Isolated murine macrophages were cultured in vitro wi th particulate titanium in order to explore the mechanism of macrophag e activation by particulate wear debris. The results, in which the amo unt of secreted, soluble collagenase in culture supernatants was inver sely proportional to titanium concentration, suggested that titanium s trongly adsorbed secreted collagenase. This inference was confirmed by direct binding assays in which particulate titanium coated with adsor bed collagenase bound an alkaline phosphatase conjugated anticollagena se antibody, but not a conjugated anti-IgG antibody. Adsorption of col lagenase was not influenced by preincubation of titanium particles wit h albumin. The adsorbed collagenase remained enzymatically active as i ndicated by its ability to hydrolyze a synthetic peptide substrate. Th ese results demonstrate that particulate titanium stimulates collagena se production by macrophages and then strongly adsorbs the secreted pr oinflammatory enzyme. The process of macrophage stimulation, collagena se secretion, and adsorption may represent an important mechanism for localization and concentration of collagenase in periprosthetic and sy novial tissue, a mechanism that ultimately triggers bone resorption th rough osteoclast activation. (C) 1994 John Wiley & Sons, Inc.