Wang Yiru, Zhang Yizhou, Shen Zhe, Qiu Yuan, Wang Chaoyang, Wu Zhifang, Shen Minjuan, Shao Changyu, Tang Ruikang, Hannig Matthias, Fu Baiping, Zhou Zihuai
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, 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, Zhejiang, 310000, China.
School of Stomatology, Hangzhou Normal University, Hangzhou, Zhejiang Province, 310000, China.
Adv Healthc Mater. 2024 Aug;13(20):e2400102. doi: 10.1002/adhm.202400102. Epub 2024 May 3.
The phosphorylated noncollagenous proteins (NCPs) play a vital role in manipulating biomineralization, while the mechanism of phosphorylation of NCPs in intrafibrillar mineralization of collagen fibril has not been completely deciphered. Poly(vinylphosphonic acid) (PVPA) and sodium trimetaphosphate (STMP) as templating analogs of NCPs induce hierarchical mineralization in cooperation with indispensable sequestration analogs such as polyacrylic acid (PAA) via polymer-induced liquid-like precursor (PILP) process. Herein, STMP-Ca and PVPA-Ca complexes are proposed to achieve rapid intrafibrillar mineralization through polyelectrolyte-Ca complexes pre-precursor (PCCP) process. This strategy is further verified effectively for remineralization of demineralized dentin matrix both in vitro and in vivo. Although STMP micromolecule fails to stabilize amorphous calcium phosphate (ACP) precursor, STMP-Ca complexes facilely permeate into intrafibrillar interstices and trigger phase transition of ACP to hydroxyapatite within collagen. In contrast, PVPA-stabilized ACP precursors lack liquid-like characteristic and crystallize outside collagen due to rigid conformation of PVPA macromolecule, while PVPA-Ca complexes infiltrate into partial intrafibrillar intervals under electrostatic attraction and osmotic pressure as evidenced by intuitionistic 3D stochastic optical reconstruction microscopy (3D-STORM). The study not only extends the variety and size range of polyelectrolyte for PCCP process but also sheds light on the role of phosphorylation for NCPs in biomineralization.
磷酸化的非胶原蛋白（NCPs）在调控生物矿化过程中起着至关重要的作用，然而，在胶原纤维的原纤维内矿化过程中NCPs的磷酸化机制尚未完全阐明。作为NCPs模板类似物的聚乙烯膦酸（PVPA）和三聚磷酸钠（STMP），通过聚合物诱导的类液前驱体（PILP）过程，与不可或缺的螯合类似物如聚丙烯酸（PAA）协同诱导分级矿化。在此，提出了STMP-Ca和PVPA-Ca复合物通过聚电解质-Ca复合物前体（PCCP）过程实现快速的原纤维内矿化。该策略在体外和体内对脱矿牙本质基质的再矿化均得到了有效验证。尽管STMP小分子无法稳定无定形磷酸钙（ACP）前驱体，但STMP-Ca复合物能轻易渗透到原纤维内间隙，并触发ACP在胶原内转变为羟基磷灰石。相比之下，PVPA稳定的ACP前驱体缺乏类液特性，由于PVPA大分子的刚性构象而在胶原外结晶，而PVPA-Ca复合物在静电吸引和渗透压作用下渗透到部分原纤维内间隙，这一点通过直观的三维随机光学重建显微镜（3D-STORM）得以证实。该研究不仅扩展了用于PCCP过程的聚电解质的种类和尺寸范围，还揭示了NCPs的磷酸化在生物矿化中的作用。
