磷酸化蛋白质仿生类似物诱导的矿化胶原支架对人牙髓干细胞成牙本质向分化作用的研究

The abilities of PAMAM dendrimers in inducing collagen mineralization are of great importance in dentin regeneration. However, intrafibrillar mineralization of collagen has not been achieved yet in current studies using PAMAM dendrimers, which may limit their applications. Whether biomimetic analogs of non-collagenous proteins based on PAMAM dendrimers could induce intrafibrillar collagen mineralization and whether the mineralized collagen could stimulate odontoblastic differentiation of human dental pulp stem cells are important for dentin regeneration. As was shown in previous studies, phosphorylated PAMAM dendrimers could induce biomimetic remineralization of demineralized dentin, under the existence of amorphous calcium phosphate stabilizing agent. Combined with the amorphous calcium phosphate stabilizing ability, phosphorylated PAMAM dendrimers were expected to have the potential in acting as bimimetic analogs of non-collagenous proteins and inducing dentin regeneration. In this study, phosphorylated PAMAM dendrimers which could act as biomimetic analogs of phosphoproteins would be synthesized via Mannich reaction. Such a target molecule will by capable to have the potentials in stabilizing amorphous calcium phosphate and inducing intra- and interfibrillar mineralization of type I collagen. In this study, mineralized collagen scaffolds are expected to be constructed by using phosphorylated PAMAM dendrimers. The roles of these mineralized collagen scaffolds in odontoblastic differentiation and mineral formation of human dental pulp stem cells will be verified as well. With the success of these studies, new ideas for biomimetic mineralization and dentin regeneration are expected to be explored.

PAMAM分子诱导胶原矿化的能力对牙本质再生具有一定意义，然而目前研究尚未经其实现胶原分子内矿化。基于PAMAM分子构建的非胶原蛋白仿生类似物能否诱导胶原分子内矿化及该矿化胶原能否刺激人牙髓干细胞成牙本质向分化对实现牙本质再生具有重要意义。本课题前期研究表明，磷酸化PAMAM分子可与无定形磷酸钙稳定剂协同作用，诱导脱矿牙本质仿生再矿化，加之该分子具有稳定无定形磷酸钙的能力，理论上可作为非胶原蛋白的仿生类似物诱导胶原分子内矿化。本课题计划通过曼尼希反应合成磷酸化PAMAM分子，构建非胶原蛋白中磷酸化蛋白质的仿生类似物。设计分子将同时具有稳定无定形磷酸钙及与I型胶原特定位点结合的能力，理论上能够诱导胶原支架分子内矿化。本课题预期利用该分子构建矿化胶原支架并验证其诱导人牙髓干细胞形成矿化物的作用，通过对矿化胶原支架刺激人牙髓干细胞成牙本质向分化机制的研究为牙本质的仿生矿化和再生提供新的思路。

内容获取失败，请点击重试