Abstract
The release of metallic elements from the surfaces of orthopaedic prostheses, either by leaching or breakdown of the device into the body, is a potential health problem to patients. During the endurance of this bio-material metal alloys undergo to corrosion with the possibility that metal ions interact with biofluids and tissues inducing adverse biological effects (local or systemic damage such as cytotoxicity, delayed hypersensitivity, effects on angiogenesis and mutagenicity). Indeed, as the metal ions are released over a period of time, they will continue to stimulate the inflammatory response and to influence those cells within the chronic response.
The safe evaluation of biocompatibility of metallic-based orthopaedic prostheses is a prerequisite for their use in medicine. In this context, the use of in vitro model systems is of growing importance, not only as components of the initial phases of the safe evaluation process, but also as alternative (non-animal) methods for regulatory purpose through the cycle of research, development, validation and acceptance by regulatory authorities.
The aim of this work is to review the activity of IMETOX (In vitro Metal Toxicology) project of ECVAM in relation to biomaterials for hard tissue substitute. The research is aiming at integrating aspects of metal toxicity in different toxicological areas (e.g. systemic toxicity, reproductive toxicity, immunotoxicity, carcinogenicity).
Examples of tier testing as basis for new in vitro strategies for the evaluation of immunotoxicity, basal cyto-toxicity, and carcinogenic potential of metals of interest as components of medical devices (e.g. Ag, Co, Cr, Pt, Ti, V) investigated by cell cultures (mouse fibroblasts Balb/3T3, human keratinocytes HaCaT) are presented.
Key factors influencing cellular metal toxicity (low dose exposure, speciation, interaction among elements) and the new emerging problems of the cytotoxic potential of metal-nanoparticles are discussed.
The abstracts were prepared by Ms Grazia Gliozzi. Correspondence should be addressed to her at the Italian Orthopaedic Research Society, Laboratory for Pathophysiology, Instituti Ortopedici Rizzoli, University of Bologna, Bologna, Italy.
