基于快速原型技术的3D生物打印系统研制及其皮肤组织工程方面应用研究

In order to solve the problem of poor control over pore size, geometry, and interconnectivity of the scaffold provided by conventional manufacturing processes and the random placement of cells within scaffolds, we propose new researching method for skin tissue engineer based on 3D printing technology in this project. And we will develop multi-arm and co-axial type 3D bioprinting system and do research on its application in skin tissue engineer. Take the methods of theoretical analysis, co-simulation and prototype trial-manufacture to design mechanical system and control program of this system; develop the slicing software with the research of adaptive slicing delaminating algorithm based on STL files ; design the nozzles based on simulation analysis with CFD software to reduce damage to cells; we will do research on the application of the 3D bioprinting system in tissue engineer and test the 3D printer. Study the experimental method of scaffold and cell printing with the 3D bioprinting system and influence on the filament and cell spheroid during the printing process to establish a database system; focus on the challenging problems, such as low cell viability and propose the methods of simulation of the force on cells, building the micro-flow channel and the manual input of nutrients and the gas to solve these problems to lay the foundation for realizing 3D bioprinting in its real sense.

针对传统支架制备方法中支架孔径大小、几何分布和连通性不均匀，细胞分布随机性等问题，本项目提出基于3D打印技术的皮肤组织工程研究方法，研制多臂式、同轴喷头型3D生物打印系统，并进行皮肤组织工程应用研究。采用理论分析、联合仿真分析和样机试制相结合的方法完成机械系统、控制程序的设计；在基于STL格式文件的自适应分层算法研究的基础上开发切片控制软件；基于CFD软件仿真分析的喷头结构设计以减少喷头对细胞的伤害。项目还将进行3D打印系统在组织工程方面应用研究，完成系统考核任务：研究3D生物打印系统用于支架/细胞打印实验方法，研究打印过程中控制参数对纤维和细胞球体参数的影响规律，建立过程参数控制数据库体系；重点研究打印过程细胞存活率低等难题的解决方案，提出细胞受力仿真、构建微流通道和人工输入养分与气体方法提高细胞活性，为实现真正意义上的3D生物打印奠定基础。

针对传统组织工程支架制备方法过程不易控制导致的支架孔径大小不均一、形状难控制和细胞分布不均的问题，本项目提出基于生物3D打印技术的皮肤组织工程支架制造方法。开展基于气动挤出原理的多喷头生物3D打印系统研制，完成了运动、供料、温控、交联和环境控制五大系统和相应软件的设计和开发，形成一套完整的生物3D打印系统；通过建立理论模型，结合仿真和实际实验结果，构建多种控制参数的预测模型指导生物水凝胶的打印过程；采用流体仿真联合实验测试的方法对喷头处的流速分布、剪切应力和挤出胀大等开展分析水凝胶挤出过程；设计多孔皮肤组织支架模型，通过细胞-水凝胶的一体化打印，构建不同形状的皮肤组织支架，结合力学性能分析，细胞存活率，细胞迁移等细胞功能检测验证打印工艺的有效性；分析细胞存活率问题，设计同轴喷头并构建不同尺寸的血管通道结构，可为组织内部细胞输送养分和氧气；通过动物实验验证组织工程支架的生物有效性。项目内容充分证明本项目所开发的生物3D打印系统及打印工艺的性能，为实现复杂器官的生物3D打印提供了理论和实践基础，具备指导意义。