材料表面拓扑形貌的细胞响应

材料的诸多因素可以影响细胞行为，其中，表面形貌的效应普遍存在，并且由于形貌改变可不涉及化学成份的改变、相应的材料改性容易最终获得批准应用。但是，相比于化学和生物因素，形貌导致的强烈的生物学效应仍待发现。申请人前期研究意外发现，在微柱阵列这种特殊的拓扑表面上，细胞核有可能发生严重的自我变形，同时细胞仍保持增殖等能力；我们还通过设计不同的微柱阵列初步实现了对于细胞核形状的控制，获得了十字交叉、方形等不寻常的细胞核形状。本申请项目拟弄清楚导致细胞核变形的材料参数的范围，考察不同细胞核形状和变形程度所对应的细胞功能响应，并研究骨髓基质干细胞等不同细胞种类的响应；进一步尝试在三维多孔支架的内表面构筑拓扑形貌，并研究支架中的细胞响应行为。基质材料以PLGA等常见的可降解高分子为主。该研究有助于理解材料物理因素对于细胞的作用，为生物材料设计提供指导。

Various material cues have been revealed to influence cell behaviors. Among those cues, the effect of topography is very important, because most of materials are microscopically rough and the topography modification could be free of change of chemical composition thus the application of the modified materials is relative easy to be approved. Nevertheless, the topography effect is,as usual, not so strong as chemical and biological factors...Very recently, the research group led by the applicant found surprisingly a serious deformation of cell nuclei when cells were cultured on some micropillar arrays of PLGA, a conventional biodegradable polymer. We further designed different patterns of the micropillar arrays and successfully controlled nucleus shapes. Some unusual shapes such as cross and square have been achieved...The present grant is aimed to determine the range of the appropriate factors to enable the interesting phenomena of self deformation of cell nuclei, to explore the responses of cells with deformed nuclei of different shapes and self-deformation contents, and to examine the cell-type dependence. We also plan to develop the technique to adjust the topography of interior surfaces of three dimensional porous scaffolds, and investigate the corresponding cell responses in large porous scaffolds. The topography effect on cell responses might be universal although commercialized PLGA will be taken as the main material matrix in our study. Our research might shed the new insight of physical cues of materials to tune cell behaviors and afford guidance in designing new biomaterials.