Hypersensitivity Associated with Metallic Biomaterials

tion of metals have been reported to cause reacBiocompatibility can be defined as the ability tions, which most typically manifest as hives, of a biomaterial to demonstrate host and material eczema, redness, and itching (6,9–11). Although response appropriate to its intended application little is known about the shortand long-term (1). The determination of biocompatibility has pharmacodynamics and bioavailabiality of circubeen dominated historically by the characterizalating metal degradation products in vivo (2,5,12– tion of candidate materials, based on the observa14), there have been many reports of immunologic tion of adverse host responses. However, some responses temporally associated with implantaadverse responses are subtler in clinical settings, tion of metal components. Individual case reports and continue to foster debate and investigation. link hypersensitivity reactions with adverse perOne of these responses is “metal allergy,” or formance of metallic cardiovascular (15–17), hypersensitivity to metallic biomaterials. orthopedic (7,18–22), and plastic surgical (23), All metals in contact with biological systems and dental (24–30) implants. corrode (1,2) and the released ions, although not Metals known as sensitizers (haptenic moieties immune sensitizers on their own, can activate the in Ags) include beryllium (31), nickel (Ni) (9– immune system, by forming complexes with 11,31), cobalt (Co), and chromium (Cr) (31). native proteins (3–5). These metal–protein comOccasional responses have been reported to tantaplexes are considered to be candidate antigens lum (32), titanium (33,34), and vanadium (V) (Ags) (or allergens) in human clinical applica(32). Ni is the most common metal sensitizer in tions. Polymers and oxide-based ceramics, such humans, followed by Co and Cr (6,9–11). Crossas alumina and zirconia, are not easily chemically sensitivity reactions between metals are also comdegraded in vivo, and have not been intensely mon, with Ni and Co the most frequently crosinvestigated as sources of allergic-type immune sreactive (6). The amounts of these metals found responses. Presumably, the relatively large in medical grade alloys are shown in Table 1. ceramic and polymeric wear debris particles do