Wu Haiyan, Shao Changyu, Shi Jue, Hu Zihe, Zhou Yanyan, Chen Zhuo, Tang Ruikang, Xie Zhijian, Jin Wenjing
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China.
Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
Carbohydr Polym. 2023 Nov 1;319:121174. doi: 10.1016/j.carbpol.2023.121174. Epub 2023 Jul 3.
Non-collagenous proteins (NCPs) in the extracellular matrix (ECM) of bone and dentin are known to play a critical regulatory role in the induction of collagen fibril mineralization and are embedded in hyaluronic acid (HA), which acts as a water-retaining glycosaminoglycan and provides necessary biochemical and biomechanical cues. Our previous study demonstrated that HA could regulate the mineralization degree and mechanical properties of collagen fibrils, yet its kinetics dynamic mechanism on mineralization is under debate. Here, we further investigated the role of HA on collagen fibril mineralization and the possible mechanism. The HA modification can significantly promote intrafibrillar collagen mineralization by reducing the electronegativity of the collagen surface to enhance calcium ions (Ca) binding capacity to create a local higher supersaturation. In addition, the HA also provides additional nucleation sites and shortens the induction time of amorphous calcium phosphate (ACP)-mediated hydroxyapatite (HAP) crystallization, which benefits mineralization. The acceleration effect of HA on intrafibrillar collagen mineralization is also confirmed in collagen hydrogel and in vitro dentin remineralization. These findings offer a physicochemical view of the regulation effect of carbohydrate polymers in the body on biomineralization, the fine prospect for an ideal biomaterial to repair collagen-mineralized tissues.
众所周知，骨骼和牙本质细胞外基质（ECM）中的非胶原蛋白（NCPs）在诱导胶原纤维矿化过程中发挥着关键的调节作用，并且嵌入透明质酸（HA）中，透明质酸作为一种保水糖胺聚糖，提供必要的生化和生物力学线索。我们之前的研究表明，HA可以调节胶原纤维的矿化程度和力学性能，但其矿化的动力学动态机制仍存在争议。在此，我们进一步研究了HA对胶原纤维矿化的作用及其可能的机制。HA修饰可以通过降低胶原表面的负电性来显著促进纤维内胶原矿化，以增强钙离子（Ca）的结合能力，从而产生局部更高的过饱和度。此外，HA还提供了额外的成核位点，并缩短了无定形磷酸钙（ACP）介导的羟基磷灰石（HAP）结晶的诱导时间，这有利于矿化。HA对纤维内胶原矿化的加速作用在胶原水凝胶和体外牙本质再矿化中也得到了证实。这些发现为体内碳水化合物聚合物对生物矿化的调节作用提供了一种物理化学观点，为修复胶原矿化组织的理想生物材料提供了良好的前景。
