Hypersensitivity to metallic biomaterials: a review of leukocyte migration inhibition assays

Metal hypersensitivity is a well-established phenomenon occurring in a variety of domestic and workplace settings. Degradation products of metallic biomaterials may mediate metal hypersensitivity. However, little is known about the short- and long-term pharmacodynamics and bioavailability of circulating metal degradation products in vivo. Mechanisms by which in vivo metal sensitivity reactions occur have not been well characterized and the degree to which metal sensitivity may be a predisposing factor for eliciting an overaggressive immune response remains clinically unpredictable. In vitro leukocyte migration inhibition assays have been used for investigating cell-mediated hypersensitivity reactions to biomaterial and biomaterial degradation products. This review provides a historical and technical summary of four in vitro techniques used for determination of leukocyte migration activity: (1) membrane migration or Boyden chamber, (2) capillary tube, (3) leukocyte migration using agarose technique, and (4) collagen gels. It is difficult to determine which, if any, of these techniques is singularly best suited for the investigation of suspected biomaterial-related symptoms in patients. However, Boyden chamber membrane migration testing is recommended for clinical investigations, principally because a high degree of standardized investigator independent materials and methodologies is necessary for compiling and comparing the results of patients tested at various times over the length of an extended study. Ultimately, in vitro migration inhibition testing has the potential to provide a reliable means for predicting some complications and thus enhancing the outcome for patients receiving metallic implants. Continuing improvements in migration inhibition testing methods, used alone or in combination with other immunologic assays, will likely improve assessment of patients susceptible to biomaterial antigen-induced delayed-type hypersensitivity responses.