基于微流控技术的生物可降解海藻酸钙微颗粒和微纤维的成型机理及结构控制研究

Calcium alginate hydrogel, which has good antibacterial ability, biocompatibility and biodegradability, is a green and environment-friendly medical functional material. Size and structure controllable calcium alginate microparticles and microfibers can broaden their applications in biomedical applications. Preparation of micro-components using microfluidic devices has low energy consumption and high resource utilization, which fits in well with the characteristics of ‘Green Manufacturing’. This project mainly studies the fabrication and structural control of calcium alginate microparticles and microfibers based on microfluidic technology, in order to develop a green manufacturing technology of micron-sized calcium alginate products..There are still some difficulties in current research: 1) calcium alginate slurry has high viscosity and is difficult to manipulate in microfluidic devices; 2) The shapes of microchannels are simple, so it is difficult to control the shapes of microfibers; 3) The research of calcium alginate phase separation material system is scant; 4) The correlation between structures and biodegradability of microparticles and microfibers is lacking. In order to solve the above problems, this project intends to focus on: 1) studying the mechanism of calcium alginate gelation process; 2) developing the texture-surface enhanced phase inversion method to fabricate high viscous microparticles; developing microchannels with complex shapes to control the shapes of microfibers; 3) designing the calcium alginate phase separation material system to realize the precise control of the structures of microparticles and microfibers; 4) exploring the fabrication method of drug-delivered microparticles and microfibers, and studying the effect of structures on the biodegradability.

海藻酸钙水凝胶具有良好的抑菌性、生物相容性和可降解性，是一种绿色环保的医用功能材料。尺寸、结构可控的海藻酸钙微颗粒和微纤维在生物医药领域具有广阔的应用前景。利用微流控技术制备微型零部件，能耗低、资源利用率高，符合绿色制造的特点。本项目主要研究基于微流控技术的海藻酸钙微颗粒和微纤维成型机理及结构调控，发展微米级海藻酸钙制品的绿色制造技术。.目前尚存以下难点：1）海藻酸钙浆料粘度高，在微流控器件中难以操控；2）微通道形状单一，不易控制微纤维形状；3）缺乏海藻酸钙相分离材料体系研究；4）缺乏结构与微颗粒和微纤维可降解性能的关联。针对上述问题，本项目拟重点研究：1）海藻酸钙凝胶机理；2）织构表面促进反相法制备高粘度微颗粒；研制复杂形状微通道，调控微纤维形状；3）设计海藻酸钙相分离材料体系，实现微颗粒和微纤维结构的精确调控；4）探究不同结构载药微颗粒和微纤维的制备工艺，研究结构对可降解性能的影响。

本项目针对海藻酸钙微颗粒、微纤维成型及结构调控方面存在如高粘度微颗粒难以成型、难以实现复杂结构微颗粒和微纤维的制备、相分离过程难以控制且相分离材料体系较少等难点，设计出了能够制备尺寸均匀、形状可控的高粘度微颗粒和微纤维的微流控器件；阐明了海藻酸钙微颗粒和微纤维微流成型的机理，建立微颗粒和微纤维在制备过程中微通道内壁面织构对液体流动状态影响的物理模型；明确了工艺参数对海藻酸钙微颗粒和微纤维结构的影响规律，实现海藻酸钙微颗粒和微纤维结构的有效调控；建立材料配伍-形状结构-可降解性能的关系模型，实现了不同应用环境下材料配伍和工艺参数的快速设计。相关数据支撑发表了17篇高水平论文，授权了8项国家发明专利，为海藻酸钙微颗粒和微纤维在药物可控释放、医用敷料等领域的应用提供实验依据及工艺方案。