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Cellular Responses at the Zirconia Dental Implant Interface: A Comprehensive Review

Milic MS, Simonovic J, Todorovic VS

Journal of functional biomaterials, 2026

Abstract

Titanium remains the gold standard in dental implantology; however, its clinical drawbacks, such as hypersensitivity reactions, metallic particle release, and aesthetically compromising discoloration, have driven interest in metal-free alternatives. Yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) has emerged as a promising bioceramic candidate, offering favorable aesthetics, mechanical strength, and reduced bacterial plaque affinity. Its pristine surface is nonetheless bioinert, prompting extensive research into surface modification strategies, including sandblasting, acid-etching, femtosecond laser texturing, and bioactive coatings, to enhance osteoconductivity. This comprehensive narrative review synthesizes in vitro evidence on the behavior of key host cell populations-macrophages, mesenchymal stem cells, osteoblasts, fibroblasts, and epithelial cells in response to Y-TZP surface and its modifications, relevant to osseointegration and soft-tissue sealing. A literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library, supplemented by Google Scholar, concluding in March 2026. By integrating findings across multiple cell lineages, this review aims to clarify how engineered zirconia topographies modulate cell-specific pathways, thereby informing the development of next-generation implants optimized for biological integration.

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