Toward clinically relevant in vitro models for dental implant integration: Methodological insights and translational perspectives

OBJECTIVES: This critical review elucidates the coordinated integration of peri‑implant bone and soft tissues by jointly addressing osseointegration, muco‑integration, and the local inflammatory response, comparing in vivo prerequisites with current in vitro models. METHODS: A comprehensive literature search was conducted in PubMed, Google Scholar, and Web of Science, focusing on in vitro studies using mammalian cells to assess metallic implant‑based materials in relation to both bone and soft tissue integration, including inflammatory and healing responses. Search terms combined biocompatibility, in vitro models, dental implants, osseointegration, muco‑integration, inflammatory response, cell-material interactions, and mechanotransduction. A total of 333 articles were selected and critically analyzed, with data integrated to establish a framework linking in vivo biological prerequisites to the performance of in vitro models. RESULTS: The analysis enabled a comparative assessment of in vivo implant integration and the corresponding in vitro models developed to reproduce these phenomena under various experimental conditions. Correlations among inflammatory responses, healing kinetics, and the evaluated cellular or molecular parameters were critically examined, with particular emphasis on the limitations of static in vitro setups in mimicking the dynamic mechanical environment encountered in vivo. The review also situates current in vitro methodologies within the ISO standard framework for biological evaluation of implantable devices, paving the way for improved standardization, reproducibility, and translational relevance. SIGNIFICANCE: This review provides an integrated perspective on the biological mechanisms governing implant integration. It highlights key cellular endpoints to enhance the predictive value and translational relevance of in vitro models in dental implant research.