聚乳酸透皮微针制品多尺度注塑成型/成性模拟及优化设计研究

Transdermal drug delivery systems (TDDS) is a modern medical trend instead of oral delivery (like pills) and injections. Nowadays, microneedle attracts people’s attention since it is minimally invasive and slightly painful. As the manufacturing technology develops, metal, silicon and polymer microneedles come into people’s life, especially the biodegradable polymer microneedle has the very good prospects among them. Polylactic acid (PLA) has good mechanical and biomedical performance, and is suitable to manufacture the microneedle by micro-injection molding. However, different from the entire product, the microneedle structure is in micrometers scale, which causes bad replication during filling..In order to overcome the manufacturing difficulty of PLA microneedle during micro-injection molding, this project is prepared to have the fundamental and deep study according to the research status at home and abroad. First of all, the mechanism of the bad replication during filling should be known. In order to overcome the difficulty of simulation on the replication of the microneedle, FEM/SPH based simulation method is investigated and developed. Then, by using the physical visualization technology of injection molding, the experimental study of the microneedle is performed to clarify the simulation result, and study the mechanism further. Second, mechanical performance of PLA can ensure the service quality during penetrating skin. It is worth to note that the mechanical performance of polymer material evolves during injection molding. Some literatures have studied this behavior of amorphous polymer. However, PLA is semi-crystal polymer, and there is no physical model to be referenced. Therefore, the rule of mechanical performance (yield stress herein) evolution of PLA is studied by combining physical aging theory and relevant experiments. Finally, a new multi-objective optimization method is studied based on the kriging surrogate model and the idea of truncated level. The aims are to improve the molding quality and mechanical performance of PLA microneedle, and give a new design criterion of the domain around the design point to satisfy the engineering demands. According to the optimization result (best processing parameters and mold design), the PLA microneedle product is tried to be produced by micro-injection molding machine finally..Overall, the theory, method and technique of this project will be a further expansion for micro-injection molding, optimization theory, etc., and promote the development of the modern medicine and polymer processing. Therefore, it has a significant meaning in the fundamental science and engineering.

研究微针充填不完整的成型机理和聚乳酸材料性能演化规律，是解决微针制品成型设计与制造问题的重要前提。针对微针结构的特殊性，本项目发展FEM/SPH多尺度成型的耦合模拟方法，结合可视化实验研究，揭示具有微凸结构制品充填不完整的成型机理；针对微针服役的材料性能要求，本项目研究材料屈服应力的演化规律及预测方法，实现制品成型过程材料成性的同步预测。为提高制品成型质量和材料性能、满足设计方案局部调整的需求，本项目研究基于kriging代理模型和截集思想的多学科多目标优化设计方法，发展确定可行方案局部可接受域的评判方法，并结合优化设计结果，研制具有优异成型/成性质量的微针制品。项目研究的理论、方法与相关技术成果是对微注塑、优化设计等领域的重要发展，并将强有力地推动现代医学微创、微痛/无痛治疗技术的发展与应用，提高医疗器械的创新能力和产业化水平，具有重要的科学研究意义和医学应用价值。

研究微针充填不完整的成型机理和聚乳酸材料性能演化规律，是解决微针制品成型设计与制造问题的重要前提。针对微针结构的特殊性，本项目发展FEM/SPH多尺度成型的耦合模拟方法，结合可视化实验研究，揭示具有微凸结构制品充填不完整的成型机理；针对微针服役的材料性能要求，本项目研究材料屈服应力的演化规律及预测方法，实现制品成型过程材料成性的同步预测。为提高制品成型质量和材料性能、满足设计方案局部调整的需求，本项目研究基于kriging代理模型和截集思想的多学科多目标优化设计方法，发展确定可行方案局部可接受域的评判方法，并结合优化设计结果，研制具有优异成型/成性质量的微针制品。项目研究的理论、方法与相关技术成果是对微注塑、优化设计等领域的重要发展，并将强有力地推动现代医学微创、微痛/无痛治疗技术的发展与应用，提高医疗器械的创新能力和产业化水平，具有重要的科学研究意义和医学应用价值。