纳米纤维素多维有序微结构的可控构建及其生物医学应用

The highly ordered self-assembled structures of naturally occurring biomaterials and soft/hard tissues provide them with numerous excellent properties. This phenomenon inspired us to fabricate multidimensional ordered micro-structured materials to achieve functional modulation. This study is aimed to develop multidimensional ordered microstructures through biofabrication, simulation, 3D printing, and multi-physical field numerical modeling. Specifically, by using 1D cellulose crystalline nanofibers (the hard component) and biomaterials, such as polysaccharides, and polyamino acid hydrogels (the soft component), we sought to build patterned 2D surfaces, ordered 3D structures, that are adaptable to transformation (4D). Moreover, we aim to develop strategies to construct novel nanocellulose-based biomaterials with multidimensional ordered microstructures and to elucidate the correlations between their molecular structures, mechanical properties and biological functions. Additionally, cells from different tissue layers can be programed to achieve directed adhesion, proliferation and differentiation, with proper multi-physical field numerical modeling. This will better mimic biological processes, such as the weight-bearing of intervertebral disc, the blood flow in the vessels, the bowel contraction and movement, and the host-microbe ecosystem. Thus, this work will provide the important scientific basis for fabrication of engineered tissues with multidimensional ordered microstructures, such as bone and cartilage tissues, intervertebral discs tissues, intestinal tissues, and blood vessels etc.

天然生物材料与组织中软硬成分的有序自组装使生物组织具有优异的综合性能。这些有序微结构的范例启发我们在对生物材料的设计需要构建多维有序微结构从而实现其功能的智能调控。本项目采用生物制造、仿生模拟、3D打印、多物理场数字建模等方法，以纤维素纳米纤维为一维刚性组分，以聚多糖、聚氨基酸凝胶等为软组织成分，构筑2D 有序界面、3D 有序微结构支架、 以及具有 4D 变形智能响应的有序微结构支架。建立基于纤维素纳米纤维的多维复杂结构的可控构建方法及多种方法的协同调控，阐明超分子结构与力学性能和生物功能之间的关系。利用多物理场数字建模，从微观上实现不同组织层细胞的定向诱导粘附、增殖与分化。宏观上实现功能上的仿生模拟，如匹配椎间盘组织的承重、血管的血流脉动、肠道的收缩和蠕动以及建立宿主-菌群微生态系统等。为构筑多维精细结构的骨和椎间盘组织、血管组织、肠道组织工程支架提供重要科学依据。

天然生物材料与组织中软硬成分的有序自组装使生物组织具有优异的综合性能。这些有序微结构的范例启发我们在对生物材料的设计需要构建多维有序微结构从而实现其功能的智能调控。本项目1)建立了以纳米纤维素、碳纳米管、聚吡咯、MXene（Ti3C2Tx）、PEDOT:PSS为硬组织材料；明胶、纤维素水凝胶、瓜尔胶、壳聚糖等为软组织成分，构筑智能电响应的结构支架的方法，探索了其皮肤组织工程修复等方面的生物医学应用。2)建立了以聚乙烯醇、壳聚糖等生物大分子的微纳米栓塞剂、药物载体以及三维细胞培养微载体，探索了其在前列腺栓塞治疗，卵巢癌诊断、细胞三维培养等方面的应用。3)并建立了一种稳定性超疏水界面的制备方法，其界面对水、组织液、血液、尿液和脓液等液体具有优异的排斥性能，并在此界面上设计了一种超疏水的液-固接触摩擦纳米发电机，研究了其作为液滴传感器在生物医学上的应用。在项目资助下，申请发明专利多项，并有3项已经获得授权；在国际高档次SCI源刊物发表论文24篇。培养博士后2名，博士5名，硕士研究生4 名。