Cell Calcification Models and Their Implications for Medicine and Biomaterial Research.

The evolutionary significance of calcium-based minerals is highlighted by the division of life between those animals with backbones (vertebrates) and those without (invertebrates). Calcification, or biomineralization, is the process by which the tissues containing minerals are formed, occurring during normal physiological processes, such as bone remodeling, or in pathological conditions, like cardiovascular calcification. The 50th anniversary of the creation of the first true calcification cell culture model was in 2024, and these have become increasingly important to many fields of research in biology and medicine. Both the literature and experimental protocols associated with cell calcification models have become extremely fragmented across the many different research streams pursued. Here, it is aimed to give a comprehensive overview of the range of models available, and the approaches taken in these models, highlighting when and how methodological divergences arise, and identifying their most common issues. Ultimately, it is aimed to propose solutions to improve both replicability and the scientific relevance of such models. Cell models are fundamental to understanding pathologies where calcification is present and to improve knowledge of the most fundamental tissues in vertebrates: bones and teeth.