Biomimetic mineralization of collagen: mechanisms, applications, and prospects

Mineralization is a prevalent phenomenon among vertebrates that involves a dynamic physical/chemical interplay between the organic and inorganic components of hard tissues. Biomimetic mineralization is a process of synthesizing inorganic minerals with the guidance of organic molecules or biomolecules under the relatively mild conditions. Intrafibrillar mineralization of collagen is essential not only as a fundamental process in forming biological hard tissues but also as a bottom-up strategy for the construction of advanced biomineralization-inspired biomaterials. This review firstly provide a brief overview of physiological and pathological mineralization, followed by systematically summarizes research progress in the representative mechanisms and hypotheses for intrafibrillar mineralization of collagen, including the classical nucleation theory, the polymer induced liquid precursor theory, the size exclusion theory, the electrostatic attraction theory, the Gibbs-Donnan equilibrium theory and the polyelectrolyte‑calcium complexes pre-precursor pathway. Then, the regulation of hierarchical macro-nano structure and its applications in tissue engineering of biomimetic mineralized collagen are outlined. Furthermore, with the advancement of protein recombination technology and the in-depth understanding of mineralization mechanism, the development of biomimetic mineralized collagen in the field of oral hard tissues is anticipated. These research progress can further inspire researchers to design structurally sophisticated and multifunctionalized biomimetic materials to meet the complex clinical requirements.