Pathophysiology of the Toxic Effects in Metallic Implants

Implants play a very crucial role in modern era of medicine and address several needs in all the medical specialties. Both essential and nonessential metals released from implants at high concentrations can impair biological functions and result in toxicity involving multiple systems of the body. Furthermore, the toxicity information is typically based on exposure through dietary intake and/or occupational/environmental exposure but, since the in vivo implant environment and its composition is different or unknown, individual implants toxic effects needs to be elaborated. Several clinical and nonclinical assessment tools are advised by FDA to evaluate biocompatibility issues, such as risk of immunological response, tissue destruction or overgrowth, and other adverse reactions. The Center for Devices and Radiological Health (CDRH) Biocompatibility Guidelines state that biocompatibility end points caused by metallic implants includes cytotoxicity, sensitization, acute and chronic systemic toxicity, pyrogenicity, genotoxicity, carcinogenicity, implantation, hemocompatibility, reproductive abnormalities, developmental toxicity and biodegradation. Exposure to metal ions which acts as haptens can lead to both local and systemic hypersensitivity reactions which are generally believed to be a Type IV (delayed hypersensitivity) response. Currently, most assessment tools of implant associated hypersensitivity are based on skin sensitization which provides further scopes for research in understanding patient specific immune response causing systemic hypersensitivity.