In experiments in vivo using diffusion chambers, the morphology and composition of calcium-containing deposits on natural and artificial biomaterials that had no direct contact with cells were studied using scanning electron microscopy with energy dispersion X-ray microanalysis. It was revealed that the formation of a protein layer containing protein-calcium complexes is the key event in biomaterial calcification. A mechanism of formation of a calcium-containing protein matrix that creates the conditions for supersaturation of the crystal-forming medium over critical value has been proposed. The formation of nuclei of insoluble calcium phosphate starts predominantly deep in an adsorbed protein layer enriched by calcium ions.