基于细菌纤维素多尺度构筑的结构仿生组织支架材料设计与制备

The purpose of this study is to design and fabrication the 3D tissue engineering scaffolds that exhibit biomimetic multi-scale structures composed of microporous structure with nanofibers for more biomimetic the native extracellular matrix (ECM). In this study, we plan to reconstruct bacterial cellulose (BC) matrix scaffolds by the indirect 3D printing technology and template biosynthesis method to control the multi-scale structures with defined macro-, micro- and nanostructure. The surface charge force will be used to control the spatial distribution of BC nanofiber network on the surface of gelatin/silk pore wall in the microporous scaffolds, which can overcome the problems of the homogeneous distribution and structure in the BC porous scaffolds. Based on the biomimetic multi-scale structure of BC composite scaffolds, we expect that the final scaffolds can enhance the cellular adhesion, proliferation, inducing the cellular migration and improving angiogenesis process. Those results may provide a new perspective and approach of tissue engineering scaffolds in tissue repair and reconstruction.

本课题以模拟天然组织细胞外基质多尺度结构为目标，采用间接三维打印技术与细菌纤维素原位模板合成技术设计并构建宏观形貌、微米级多孔、纳米级纤维可控的细菌纤维素基仿生组织支架材料。利用表面电荷作用，调控纳米纤维在多孔支架内的空间分布，克服目前细菌纤维素多孔支架中纳米纤维分布均质化、纤维结构调控方法有限的难题。通过细菌纤维素基支架材料多尺度仿生构筑，使支架材料具有促进细胞黏附、增殖、导向细胞迁移及加快血管化的功能，为其在组织重建中的应用提供理论与实验基础。

本项目系统建立了细菌纤维素基多尺度结构仿生组织工程支架的设计与构筑方法。通过医学影像与天然尿道组织细胞外基质结构分析，层次设计了仿生尿道组织支架多尺度结构。利用细菌在多孔模板的静电吸附作用，通过调节初始菌种密度、复合多孔模板中混合比例，实现了多孔支架内细菌纤维素纳米纤维的密度以及疏密分布的调控，证实了空间纳米纤维结构对细胞行为的影响，细菌纤维素基多尺度结构仿生组织工程支架具有促进细胞黏附、增殖、导向细胞迁移及加快血管化的功能。以蚕丝蛋白为模板，制备了具有疏密双层结构的仿生尿道组织支架，实现了长段（5cm）尿道缺损修复。利用膀胱脱细胞基质与细菌纤维素微纤复合，探索构建了结构与成份高度仿生的尿道组织支架，并成功修复兔尿道组织缺损。为细菌纤维素组织工程支架进入临床实验提供了理论与实验基础。