In daily clinical practice, there is a notable variety of synthetic bone substitute, with various resorption rates, different chemical and structural characteristics that influence on bone regeneration and are not suitable for every clinical use. New biomaterials based on nanotechnology have been developed to be bioabsorbable as new bone is formed. This study intends to evaluate THP‐1 cell viability when exposed to extracts of unsintered nanostructured carbonated hydroxyapatite (cHA) microspheres processed at 5 and 37°C compared to sintered hydroxyapatite processed at 90°C. cHA shows, in previous studies, biocompatibility, and better bioabsorption rates, consequently, improve the deposition of new bone and tissue repair. The results demonstrated that the tested biomaterials did not activate inflammatory role through THP‐1 cells and did not affect activated macrophages independently of their crystallinities, suggesting their safety and biocompatibility. These results are of fundamental importance for the advancement of research on smart materials, especially in what controls the effect of nanostructured cHA microspheres in the biological environment, seems to be a promising biomaterial in clinical application on regenerative medicine.