聚合物胶体微粒理化性质调控干细胞胞吞和分化行为研究

Study the impact of cell uptake of colloidal particles on the differentiation of stem cells can provide in-depth understanding of the safety issue of colloidal particles and develop new biomaterials with the ability to control stem cell fate. In this project, colloidal particles with defined size, shape, mechanical property and cytophilicity will be prepared. Their impact on the differentiation of bone marrow stem cells and neuronal stem cells will be studied. The key signal pathways regulating stem cells differentiation will be elucidated as well. The molecular mechanism regarding stem cells differentiation modulated by physiochemical properties of particles will be summarized after careful study of.the interaction between particles and intracellular organism and functional biomolecules. Since the structure and property of functional colloidal biomaterials usually changes during their application, their interactions with cells should change accordingly. As a result, the impact of colloidal particles on stem cell differentiation might change as well. Therefore, the colloidal particles with defined degradability will be chosen as the candidates as stimulus responsive particles. Their impact on stem cell differentiation will be studied. Finally, a theory relating stem cell differentiation and cell uptake of colloidal particles and the interactions between particles and intracellular components will be proposed.

研究干细胞吞噬聚合物胶体微粒对其分化行为的影响规律和分子机制，不仅可以发展新型的生物材料调控干细胞的分化方向，而且也可以深入理解胶体微粒的生物安全性。本项目拟制备具有可控尺寸、形状、机械性能和细胞亲和性的聚合物胶体微粒，阐明微粒理化性质对骨髓间充质干细胞和神经干细胞分化方向和程度的影响规律。揭示调控干细胞分化的关键信号通路。通过研究胶体微粒的胞吞过程及其与干细胞内器官及生物活性分子的相互作用，阐明胶体微粒影响干细胞分化的分子机制。功能胶体微粒在使用过程中往往会发生结构性能的变化，因此微粒与细胞的相互作用必然也会随之改变，从而有可能改变微粒对干细胞分化的影响。因此本项目还将选取具有可控降解性能的胶体微粒作为代表，研究微粒在细胞内的降解行为对干细胞分化的影响规律。初步建立微粒理化性质调控干细胞胞吞和细胞内环境，进而调控干细胞分化的理论。

围绕纳米微粒调控骨髓间充质干细胞内吞进而影响其分化行为的需要，制备多种功能纳米材料，获得了其对细胞内吞、增殖、迁移和分化的影响规律。据此设计了可在体内调控骨髓间充质干细胞和肌腱干细胞分化的纳米材料，进而促进椎间盘和肌腱修复再生。.在项目资助下，作为（共同）通讯作者发表SCI论文23篇，其中包括2篇Nature Communications、1篇JACS、1篇Advanced Materials、1篇ACS Nano、1篇Chemistry Materials和1篇Biomaterials。部分研究成果通过微信公众号、科技网站等途径向大众宣传。申报中国发明专利4件、美国发明专利1件。项目负责人2018年获得基金委优秀青年项目的资助，2017年获得华人生物材料学会颁发的“青年学者奖”，2018年获得浙江省自然科学一等奖1项（排名第二），2019年获得中国生物材料学会生物医用高分子材料分会颁发的“青年学者优秀奖”。项目资助下有三位硕士研究生毕业（陈瑛、陈津、赵馨莲）。项目负责人与美国工程院外籍院士、葡萄牙米尼奥大学的副校长Rui Reis教授在纳米材料调控干细胞分化行为方面开展了深入的合作；与俄罗斯斯科尔科沃科技学院的Yuri Kotelevtsev教授在生物信息学方面展开了合作。项目负责人在国内外学术会议做邀请报告16次。