纳米纤维素/PEGDA可调控泊松比三维生物支架设计与光固化成形机理

The integration of material/structure/ processing is undoubtedly an ideal way to fabricate novel tissue engineering(TE) scaffold with high performance and bionic characteristics, and 3D printing makes it possible. However the existing 3D printing technology is not fully advanced and still has a great research space for improvement in the multi-material formation mechanism and multi-scale structure control. Due to the intrinsic characteristics, such as high connective nano-scale pores structure, outstanding mechanical properties and biocompatibility, cellulose nanofibers (CNFs), a plentiful natural material derived from plant, will be combined with a biodegradable synthetic material- poly (ethylene glycol) diacrylate (PEGDA) which is possessing high photosensitivity and mechanical performance. The purpose of this combination is to construct a new type of UV curable CNFs/PEGDA materials for TE scaffold fabrication based on stereolithography. The above research has great significance both in tissue engineering and bio-manufacturing. The main contents of the program are organized as the following：By mimicking the Poisson’s ratio control mechanism in plant tissue, as well as the structures under both the microscope and nanoscale, bionic grid structure with special Poisson’s ratio which is more favorable for the behavior and growth of the host tissue will be designed. The curing mechanism of CNFs/PEGDA composite materials will be studied by integrating the illumination, curing, shrinkage and warping model. And the relationship between material composition, process parameters and forming accuracy will be explored as well. The effects of porous structure on stem cell growth and differentiation under micro and nano-scale with variable Poisson’s ratio will also be investigated through stem cell culture experiment. The interaction mechanism of multi-scale structure, mechanical behavior and biological effect of scaffolds will be obtained to provide the theoretical guidance for the design and fabrication of biological scaffolds with high performance.

材料/结构/成形一体化无疑是高性能生物支架实现的理想途径，而三维打印使之成为可能。但现有三维打印在多材料成形机理和多尺度结构调控等方面仍存在极大研究空间。项目针对来源丰富的纳米纤维素所具有的纳米级高连通孔隙结构、优异机械性能和自然属性，将其与感光属性和力学性能优良的可降解合成材料PEGDA复合，构建可光固化3D打印的新型CNFs/PEGDA支架材料体系，对组织工程和生物制造均具有重要研究价值。项目仿效植物组织特有的泊松比调控机制，兼顾微纳尺度下的孔隙结构，仿生设计有利于宿主组织行为和生长的泊松比结构；集成光照、固化、收缩、翘曲模型，研究CNFs/PEGDA复合材料的光固化成形机理，探索材料组分、工艺参数与成形精度的关系；通过干细胞培养，探索微米级变泊松比孔结构和纳米级孔系对干细胞生长、分化的影响，获得支架多尺度结构、力学行为与生物效应的相互作用机理，从理论上指导高性能生物支架的设计。

本课题采用天然植物纳米纤维素与具有可见光固化的聚乙二醇二丙烯酸酯（PEGDA）共混，得到一种新型组织工程支架制备用复合材料，通过实验证明了PEGDA的含量是影响生物支架孔隙率及压缩模量的关键因素；引入变泊松比结构于组织工程支架设计中，以模拟天然组织的力学环境，仿真和实验数据表明变泊松比结构参数L、t、α以及材料固有属性对生物支架的弹性模量、泊松比和孔隙率具有突出的影响，对结构参数的调控可有效提升变泊松比支架的力学性能；采用自研光固化3D打印技术制备了具有变泊松比结构的PEGDA/CNF生物支架，并针对打印过程的精度问题提出了多种掩膜优化策略，提高了支架结构的固化还原度，同时可减少相邻光强能量的重叠影响；最后，生物培养及软骨分化实验验证了变泊松比结构生物支架具有更好的引导增殖分化作用，数据表明零泊松比结构生物支架相比普通正泊松比结构支架更能诱导小鼠软骨分化。本课题提出并实现了变泊松比生物支架的材料-结构-成型一体化，为高性能生物支架的实现提供了理想途径，在生物组织工程、生物医疗和植入可穿戴器件等领域表现出很好的发展潜力和应用前景，为应对未来智能医疗及生物工程难题提供一套新的解决方案。