基于线型光响应液晶高分子的动态体外血管模型构筑及应用

In vitro blood vessel model is a powerful research model for vascular-related diseases and their drug development. Incorporating smart materials into the construction of in vitro blood vessel models will allow for the easy control of their dynamic response to mimic the performance of blood vessels under physiological conditions. This project aims to prepare a novel dynamic light-manipulating in vitro blood vessel model with the aid of photoresponsive linear liquid crystal polymers (LLCPs). By ring-opening metathesis copolymerization, various LLCPs with different structures will be designed and synthesized to understand the structural effect upon their mechanical properties and photoresponsive behaviors. In combination of LLCPs, commercial microtubular materials and biocompatible materials, a composite scaffold will be fabricated to construct the in vitro blood vessel model. With the regulation of the interfaces among materials, the composite scaffold will be optimized for the overall biocompatibility, physical and chemical properties. Then, in vitro 3D cell culture of vascular endothelial cells onto this scaffold will lead to the construction of the blood vessel model with dynamic light-induced deformability. Through the local light-manipulating of this model, the in vitro dynamic mimic of blood vessels can be realized, allowing the study on the morphology and function changes of vascular endothelial cells under dynamic stress. This project will further expand the material basis for in vitro blood vessel models. Moreover, the viable control mechanism through light may open up a new platform for the dynamic manipulation of in vitro blood vessel models.

体外血管模型在血管相关疾病及其药物研发过程发挥着重要作用。利用智能材料制备动态响应的体外血管模型不仅可以为血管结构仿生提供简便的构筑方法，还有望模拟血管在生理条件下的动态行为。本项目拟利用开环易位共聚制备不同类别的线型光响应液晶高分子，精确调控其结构与性能，着重研究分子结构对光响应高分子力学性能及光响应形变行为的影响因素。通过结合商用微管材料及生物相容性材料，制备三维管状骨架模拟人体血管结构，掌握不同材料界面贴合能力与材料表面生物相容性的调控与优化机制，匹配各材料物理及化学性质。进而引入血管内皮细胞，实现其体外三维培养，构筑具有光控动态形变能力的体外血管模型，并通过局部光照操控其动态形变，实现血管多种动态过程的仿生，从而掌握血管内皮细胞在动态环境下的形态与功能变化。本项目有望进一步拓展体外血管模型的材料选择，为动态体外血管模型提供新的调控机制。

利用光响应高分子构筑体外血管模型可以在模仿血管结构的基础上，仿生其生理动态行为。本项目利用开环易位共聚和逐步加成聚合的方式制备了两类线型光响应高分子。通过第二共聚单体的引入，精确调控了这些智能材料的热力学性能及光控形变能力，初步掌握了调控这些光响应线型高分子性能的原理。接着，通过引入人血管内皮细胞实现在体外培养，评估了这些材料的细胞相容性，并针对材料在细胞培养过程中的潜在风险，利用大分子修饰改性材料表面，优化其亲疏水性能及生物相容性。进而，通过研究这类材料与商用微管材料复合工艺及界面匹配性，提出利用光流体化效应实现界面光修复，解决复合材料界面潜在剥离脱落的问题。最后，利用这些材料的加工优势，制备了多种具有光致形变特点的复杂三维仿生模型，并结合商用微管，仿生血管结构与功能，构筑了一种多层三维微管执行器，模拟了血管舒张及血液流动、循环等过程。本项目开发的光响应线型高分子共聚物可以扩充现有智能材料库，拓展其在生物医药领域的应用，简化现有体外血管模型的设计及操控设备，有望对相关疾病的药物研发提供模型，也将给生物诊疗及可穿戴医疗设备提供新的材料选择。