Adsorption of collagenase to particulate titanium: A possible mechanism for collagenase localization in periprosthetic tissue

Abstract

Osteolysis is a central feature of aseptic loosening of orthopaedic joint prostheses. This destructive process is believed to result from phagocytosis of implant wear debris by periprosthetic and synovial macrophages and the subsequent release of proinflammatory mediators, including collagenase. Isolated murine macrophages were cultured in vitro with particulate titanium in order to explore the mechanism of macrophage activation by particulate wear debris. The results, in which the amount of secreted, soluble collagenase in culture supernatants was inversely proportional to titanium concentration, suggested that titanium strongly adsorbed secreted collagenase. This inference was confirmed by direct binding assays in which particulate titanium coated with adsorbed collagenase bound an alkaline phosphatase conjugated anti-collagenase antibody, but not a conjugated anti-IgG antibody. Adsorption of collagenase was not influenced by preincubation of titanium particles with albumin. The adsorbed collagenase remained enzymatically active as indicated by its ability to hydrolyze a synthetic peptide substrate. These results demonstrate that particulate titanium stimulates collagenase production by macrophages and then strongly adsorbs the secreted proinflammatory enzyme. The process of macrophage stimulation, collagenase secretion, and adsorption may represent an important mechanism for localization and concentration of collagenase in periprosthetic and synovial tissue, a mechanism that ultimately triggers bone resorption through osteoclast activation.

Inflammatory Response to Metals and Ceramics

“…That metal particles could be dangerous to tissues through different mechanisms was suggested by Kane et al (1994), who found titanium particles promoting first collagenase production by macrophages and then strong adsorption of it onto the surface: the enzyme may be responsible for local bone resorption.…”

Surface modification of titanium, titanium alloys, and related materials for biomedical applications

“…Titanium readily adsorbs proteins from biological fluids. For instance, some specific proteins including albumin [43,44], laminin V [45], glycosaminoglycans [46], collagenase [47], fibronectin [48], complement proteins [49], and fibrinogen [50] have been found to adsorb onto titanium surface. Titanium surfaces can also support cell growth and differentiation.…”

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in joint fluid of the patients with loose artificial hip joints

“…Cyclic mechanical loading, synovial fluid pressure waves, and the natural interface surface formed between the implant and host might favor a combined mechanical and biological dissection along this interface. The binding of collagenases to titanium, 40 and possibly to other biomaterials as well, may further augment this effect. Therefore, the synovial tissue-derived, fluidphase MMPs might contribute to the aseptic loosening of THA.…”