Toxicity, Irritation, and Allergy of Metal Implants: Historical Perspective and Modern Solutions

The widespread adoption of metal implants in orthopaedics and dentistry has revolutionized medical treatments, but concerns remain regarding their biocompatibility, toxicity, and immunogenicity. This study conducts a comprehensive literature review of traditional biomaterials used in orthopaedic surgery and traumatology, with a particular focus on their historical development and biological interactions. Research articles were gathered from PubMed and Web of Science databases using keyword combinations such as “toxicity, irritation, allergy, biomaterials, corrosion, implants, orthopaedic surgery, biocompatible materials, steel, alloys, material properties, applications, implantology, and surface modification”. An initial pool of 400 articles was screened by independent reviewers based on predefined inclusion and exclusion criteria, resulting in 160 relevant articles covering research from 1950 to 2025. This paper explores the electrochemical processes of metals like iron, titanium, aluminium, cobalt, molybdenum, nickel, and chromium post-implantation, which cause ion release and wear debris formation. These metal ions interact with biological molecules, triggering localized irritation, inflammatory responses, and immune-mediated hypersensitivity. Unlike existing reviews, this paper highlights how metal–protein interactions can form antigenic complexes, contributing to delayed hypersensitivity and complications such as peri-implant osteolysis and implant failure. While titanium is traditionally considered bioinert, emerging evidence suggests that under certain conditions, even inert metals can induce adverse biological effects. Furthermore, this review emphasizes the role of oxidative stress, illustrating how metal ion release and systemic toxicity contribute to long-term health risks. It also uncovers the underappreciated genotoxic and cytotoxic effects of metal ions on cellular metabolism, shedding light on potential long-term repercussions. By integrating a rigorous methodological approach with an in-depth exploration of metal-induced biological responses, this paper offers a more nuanced perspective on the complex interplay between metal implants and human biology, advancing the discourse on implant safety and material innovation.