Hydroxyapatite (HAp) is a major inorganic component in bone minerals and is often used for bone tissue engineering. Herein, we synthesized HAp using sebacic acid as an additive at different pH values by a hydrothermal method. Sebacic acid, which has two carboxyl group ends of the carbonate chain, binds with Ca ions during the hydrothermal process to become a crystal nucleation site in (001) and at the same time could act as an inhibitor in a specific direction [i.e., (110)] for the HAp crystal growth. Sebacic acid and the hydroxyl ion (OH – ) are competitively attracted to the a ( b )-plane of HAp. Depending on the pH condition, the crystal growth resulted in different morphologies depending on the ratio of sebacic acid and hydroxide ions. It was confirmed through Fourier-transform infrared spectroscopy and Raman spectroscopy that dicalcium phosphate anhydrous with HPO 4 was produced under acidic conditions and HAp was produced under neutral and basic conditions. The plate- and nanorod-HAp crystals’ preferential growth along the c -axis, which were obtained under neutral and basic conditions, was analyzed by transmission electron microscopy. Growth control in the c -axis direction of HAp is necessary for the understanding of crystallization of bone minerals because the mineral inside the collagen fibrils in bone tissue also shows a c -axis orientation.

Mineralized collagen fibrils are important basic building blocks of calcified tissues, such as bone and dentin. Polydopamine (PDA) can introduce functional groups, i.e., hydroxyl and amine groups, on the surfaces of type I collagen (Col-I) as possible nucleation sites of calcium phosphate (CaP) crystallization. Molecular bindings in between PDA and Col-I fibrils (Col-PDA) have been found to significantly reduce the interfacial energy. The wetting effect, mainly hydrophilicity due to the functional groups, escalates the degree of mineralization. The assembly of Col-I molecules into fibrils was initiated at the designated number of collagenous molecules and PDA. In contrast to the infiltration of amorphous calcium phosphate (ACP) precursors into the Col-I matrix by polyaspartic acid (pAsp), this collagen assembly process allows nucleation and ACP to exist in advance by PDA in the intrafibrillar matrix. PDA bound to specific sites, i.e., gap and overlap zones, by the regular arrangement of Col-I fibrils enhanced ACP nucleation and thus mineralization. As a result, the c-axis-oriented platelets of crystalline hydroxyapatite in the Col-I fibril matrix were observed in the enhanced mineralization through PDA functionalization.

Mineralized fibrils are important building blocks in bone tissue, formed by the hierarchical assembly of collagen molecules and crystalline hydroxyapatite (HAp). The mineralization pathway of HAp is reported as a nonclassical‐crystallization, but the nanoconfined crystallization in collagen fibrils remains poorly understood. The mechanism of intrafibrillar mineralization of collagen‐PDA fibrils in modified‐simulated body fluid (m‐SBF) solution is studied. Collagen‐amorphous calcium phosphate (ACP) fibrils are obtained by assembling collagen‐PDA fibrils with polyaspartic acid (pAsp) as a stabilizer. The ACP undergoes a phase transformation to HAp within the fibrils upon adjusting the phosphate concentration. It is found that the phase transformation of ACP to HAp in collagen fibrils can be accelerated with a 12 h incubation with 1/10 ratio of Ca2+ to [PO4]3−. A lower ratio of 1/1 and 1/5 results in a much slower phase transformation. This finding suggests that an elevated concentration of [PO4]3− is crucial for faster phase transformation. The relationship between the crystallization rate of HAp in the fibrils and the degree of mineralization is found to be linear in all cases, indicating an interface‐controlled process. This gives a better understanding of the mechanism of HAp mineralization in collagen fibrils, providing an effective approach to material design.