Hypersensitivity to metallic biomaterials: a review of leukocyte migrationinhibition assays

Metal hypersensitivity is a well-established phenomenon occurring in a vari ety of domestic and workplace settings. Degradation products of metallic bi omaterials may mediate metal hypersensitivity. However, little is known abo ut the short- and long-term pharmacodynamics and bioavailability of circula ting 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 o veraggressive immune response remains clinically unpredictable. In vitro le ukocyte migration inhibition assays have been used for investigating cell-m ediated hypersensitivity reactions to biomaterial and biomaterial degradati on products. This review provides a historical and technical summary of fou r in vitro techniques used for determination of leukocyte migration activit y: (1) membrane migration or Boyden chamber, (2) capillary tube, (3) leukoc yte migration using agarose technique, and (4) collagen gels. It is difficu lt to determine which, if any, of these techniques is singularly best suite d for the investigation of suspected biomaterial-related symptoms in patien ts. However, Boyden chamber membrane migration testing is recommended for c linical investigations, principally because a high degree of standardized i nvestigator independent materials and methodologies is necessary for compil ing and comparing the results of patients tested at various times over the length of an extended study. Ultimately, in vitro migration inhibition test ing has the potential to provide a reliable means for predicting some compl ications and thus enhancing the outcome for patients receiving metallic imp lants. Continuing improvements in migration inhibition testing methods, use d alone or in combination with other immunologic assays, will likely improv e assessment of patients susceptible to biomaterial antigen-induced delayed -type hypersensitivity responses. (C) 2000 Elsevier Science Ltd. All rights reserved.