智能响应性梯度医用高分子及其调控细胞迁移行为研究

细胞迁移是一个重要的生物学和生理过程，与免疫反应、创伤愈合和肿瘤转移等密切相关。细胞迁移行为受各类生物、化学、物理和基质软硬梯度信号的影响；同时细胞分泌细胞外基质，重塑甚至改变细胞外基质环境。本项目将制备具有智能响应性梯度材料，包括具有刺激响应性能、自适应性能和细胞选择性的梯度医用高分子材料；模拟体内环境，采用单细胞模型和细胞片、细胞团模型，研究智能响应性梯度材料对细胞迁移行为的调控规律和原理；阐明材料智能响应和细胞培养前后表面粘附的蛋白质的主要种类、数量和构象的时空演化规律，建立响应性梯度生物材料调控细胞迁移的方法、模型和理论；探索具有梯度和取向结构的可降解材料在典型组织如血管和神经修复中的应用。智能响应性梯度材料可以更好地模拟细胞外基质的结构和性能随时间和空间的演化过程，提高梯度材料对复杂生理环境的适应性，从而为新一代组织修复和再生材料的设计和研发提供必要的理论和实验依据。

The cell migration is one of the important processes in biology and physiology, and takes a pivotal role in immune response, would healing and tumor metastasis. While it is mediated by various gradient cues including biological, chemical, physical, and matrix signals, the cell milieu is in turn remodeled as a result of dynamic secretion of extracellular matrix by cells. In this study, intelligent and gradient polymeric biomaterials such as stimuli-responsive, adaptive and cell-selective gradient biomaterials shall be prepared and used to regulate cell migration in an intelligent manner. To better mimic the physiological milieu in vivo, the models of single cell, cell sheet and cell clusters shall be adopted to explore the phenomena, discipline and mechanism of cell migration on the intelligent and gradient biomaterials. Adsorption of key proteins and their spatial and time evolution on the gradient biomaterials before and after the intelligent response and cell culture shall be clarified, which can be further correlated with the cell migration behaviors to figure out the mediating methods and models of the intelligent and gradient biomaterials. The gradient biomaterials with spatially aligned physical features are intended to be applied for repair and regeneration of typical tissues such as blood vessel and nerve in vivo. In summary, the intelligent and gradient biomaterials can better mimic the spatial and time evolution of extracellular matrixes in terms of structures and functions, enable the biomaterials with adaptivity to the complex milieu in vivo, and thereby are instructive to the design of a new generation of biomaterials for tissue repair and regeneration.