Center for Biomaterials and Biopathways, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027, P. R. China.
Department of Prosthodontics, Hospital of Stomatology Affiliated to Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, P. R. China.
Adv Mater. 2018 Feb;30(8). doi: 10.1002/adma.201704876. Epub 2018 Jan 8.
Biological hard tissues such as bones always contain extremely high levels of citrate, which is believed to play an important role in bone formation as well as in osteoporosis treatments. However, its mechanism on biomineralization is not elucidated. Here, it is found that the adsorbed citrate molecules on collagen fibrils can significantly reduce the interfacial energy between the biological matrix and the amorphous calcium phosphate precursor to enhance their wetting effect at the early biomineralization stage, sequentially facilitating the intrafibrillar formation of hydroxyapatite to produce an inorganic-organic composite. It is demonstrated experimentally that only collagen fibrils containing ≈8.2 wt% of bound citrate (close to the level in biological bone) can reach the full mineralization as those in natural bones. The effect of citrate on the promotion of the collagen mineralization degree is also confirmed by in vitro dentin repair. This finding demonstrates the importance of interfacial controls in biomineralization and more generally, provides a physicochemical view about the regulation effect of small biomolecules on the biomineralization front.
生物硬组织（如骨骼）中通常含有极高水平的柠檬酸，这被认为在骨形成以及骨质疏松症治疗中发挥着重要作用。然而，其在生物矿化过程中的机制尚未阐明。本研究发现，吸附在胶原纤维上的柠檬酸分子可显著降低生物基质与无定形磷酸钙前体之间的界面能，增强其在早期生物矿化阶段的润湿性，从而促进纤维内羟基磷灰石的形成，生成无机-有机复合材料。实验证实，只有结合约 8.2wt%柠檬酸的胶原纤维（接近生物骨中的水平）才能达到与天然骨完全矿化的程度。柠檬酸对促进胶原矿化程度的影响也通过体外牙本质修复得到了证实。这一发现表明界面控制在生物矿化过程中的重要性，更普遍地，为小分子对生物矿化前沿的调控作用提供了一种物理化学的观点。
