面向组织工程支架的具有纳米纤维结构的微米丝成型机理及工艺研究

Scaffold supports cell adhesion as a temporary Extracellular matrix, which plays a key role in tissue engineering and Regenerative Medicine. Cell lives in a vivo nano-fibrous Extracellular matrix. The scaffold composed of micro fibers which have nanofibrous morphology similar with vivo is an ideal environment for cell. While, the micro fibers with nanofibrous morphology fabrication faces a challenge. Grain growth is cannot controlled well in the material solidified process for solvent select and process parameters configuration. Solvent is selected based on Molecular dynamics simulations in this project. The solvent crystallization induced macromolecule self-assembly is researched. Ultrasound Crystallization effect is used to invent crystal nucleation. The method of Solvent grain refinement and polymer chain piled up control is researched for retaining self-assembly status of polymer chain. Multi-physical coupled fields composed of Phase change、temperature、stress field is established. Process parameters configuration is Optimized with this model. The manufacturing mechanism of micro fiber with nanofibrous morphology is revealed. It will breakthrough the fabrication merged with macro、micro and nano scales in scaffold manufacturing. It must will be a milestone of scaffold biomanufacturing.

组织工程支架为细胞提供临时性的支撑，它在组织再生医学领域中具有核心地位；纳米纤维细胞外基质是体内细胞生长的自然环境，具有纳米纤维结构的微米丝形态构成的支架是细胞三维生长的理想环境。但是目前带有纳米纤维结构的微米丝的加工尚存在由于溶剂配置和工艺手段控制导致的挤出固化过程中的析出溶剂晶粒生长难以控制的挑战，成为制约其成型过程的技术瓶颈。本项目基于粗粒化模型的分子动力学方法实施溶剂选取，研究溶剂结晶固化诱导高分子自组装形成纳米纤维的机理；采用超声结晶效应干预形核，研究溶液固化过程中溶剂晶粒细化、高分子链挤压抑制方法，维持高分子链的纳米自组装形态；建立微细挤出过程相变、温度和应力等多物理场耦合模型，实现成型工艺的温度速度等参数优化，揭示微尺度条件下带有纳米纤维结构微米丝的成型机理。这将突破目前支架加工宏观、微观、纳米三个尺度难以融合一体加工的现状，对组织工程支架制造具有里程碑式的意义。

组织工程支架为细胞提供临时性的支撑，它在组织再生医学领域中具有核心地位；纳米纤维细胞外基质是体内细胞生长的自然环境，具有纳米纤维结构的微米丝形态构成的支架是细胞三维生长的理想环境。但是目前带有纳米纤维结构的微米丝的加工尚存在由于溶液配置和工艺手段控制导致的挤出固化过程中分子组装难以控制的挑战，成为制约其成型过程的技术瓶颈。本项目基于超声结晶效应干预形核及高分子链组装，研究溶液固化过程中高分子链的纳米自组装形态；建立微细挤出过程相变、温度和应力等多物理场耦合模型， 实现成型工艺的温度速度等参数优化，揭示微尺度条件下带有纳米纤维结构微米丝的成型机理。突破了目前支架加工宏观、微观、纳米三个尺度难以融合一体加工的现状，对组织工程支架制造具有里程碑式的意义.得出以下重要结果及关键数据: 实现了30微米生物材料丝材精准3D打印,基于该微尺度三维结构,实现了骨髓间充质干细胞体外培养30天后的诱导成骨分化,整体成果处于国际领先水平.