is a common and popular biomaterial for bone regeneration. About 70% of bone structure and essentially all of the enamel in teeth are composed of HA. It has been used in orthopedic and dental applications such as dental implants, bone grafts, orthopedic implants, and bone scaffolds. [1][2][3][4][5] The reason is the excellent bioactivity, adequate mechanical characteristics, osteoconductive, and angiogenic properties, without toxicity, inflammatory, or antigenic reactions. 6 Nano-hydroxyapatite (nano-HA), particularly, is considered as one of the most biocompatible and bioactive materials that has been used and accepted in orthopedics and dentistry. [7][8][9] For example, it has been extensively used in periodontics and in oral and maxillofacial surgical procedures. The inorganic part of bone extra cellular matrix (ECM) contains nano-sized crystallites of calcium phosphate similar to HA. 10 Nano-HA has an outstanding osteoinductive capacity and improves bone-to-implant integration. 11 This nanomaterial also has been employed in the products used for oral care to treat the dentin hypersensitivity (DH) and promote enamel demineralization. It has been shown that nano-HA is capable of reducing the pain associated with DH because the nanoparticles are very small and can readily enter and fill the tubules in dentin. These nanoparticles precipitate inside the dentin tubules and block the nerves interaction with the external stimuli. They can also set down onto the surface of enamel and demineralize the early enamel caries, leading to a new apatite layer formation, which subsequently increases the enamel surface hardness and therefore prevents the tooth decay. These benefits are due to high similarity of morphology and crystal structure of nano-HA with tooth enamel. 12,13 HA can be simply synthesized or extracted from the natural sources, including eggshell, seashell, bovine, or fish bones. [14][15][16][17][18] Fish bone as an alternative natural source for HA production recently has received a lot of attention because of low cost and easy manufacturing regarding the many