两性pH敏感凝胶组织工程支架失稳特征与演化规律研究

The loss or failure of an organ or tissue is one of the main harms in human health, and tissue engineering is an effective way to solve this problem. Nevertheless, hydrogels used as scaffolds for tissue engineering are easy to generate buckling or wrinkle instability, which greatly limiting the utilization of hydrogels as tissue engineering scaffolds. This research project focus on the instability characteristic and evolutional law of polyampholytic pH-sensitive hydrogels used as tissue engineering scaffolds under coupling multi-field effect, these polyampholytic pH-sensitive hydrogels which are made by the cross-linking reactions of chitosan hydrogels with genipin. The research contents include as following: the theory analysis and calculation of the migration rule of the solvent and ions in the hydrogel and the coupling relation between the migration of these components and large deformation of the hydrogel; the derivation of the distribution rule of the charge and electric potential within the electric double layer near the solid-liquid interface and the building of a new and practical free energy function for polyampholytic pH-sensitive hydrogels; the establishment of the mechanical modeling and the corresponding boundary and initial conditions; by means of numerical simulation and experiment, a quantitative prediction model will also be set up for analyzing the influences of pH, physical properties and geometric configuration on the instability behaviors of polyampholytic pH-sensitive hydrogels. Summarily speaking, this project aims to reveal the instability characteristic and evolutional law of polyampholytic pH-sensitive hydrogels and lay a theoretical and technological foundation for controlling the instabilities of tissue engineering scaffolds and developing desirable scaffolds for tissue engineering.

组织、器官的丧失或功能障碍是人类健康所面临的主要危害之一，组织工程是解决该问题的有效途径。然而，组织工程用凝胶支架材料易发生屈曲、起皱等失稳行为，制约了该类支架材料在组织工程中的应用。本项目以京尼平交联改性后的壳聚糖两性pH敏感凝胶支架为研究对象，对多场耦合作用下的两性pH敏感凝胶的失稳特征与演化规律进行研究。具体内容包括：理论分析、计算凝胶内溶剂、离子的迁移规律及其与凝胶网络溶胀、大变形的耦合关系；研究凝胶界面附近双电层内的电荷、电势分布规律，构建符合实际的凝胶自由能函数；研究两性pH敏感凝胶支架材料失稳的力学建模及其边界条件与初始条件，结合凝胶失稳实验，建立基于环境pH值、支架的物理属性和构型几何等复杂耦合多因素的两性pH敏感凝胶支架失稳的定量预测模型。本项目旨在揭示两性pH敏感凝胶支架材料的失稳规律，为有效控制组织工程用支架材料的失稳和研制出符合实际需要的支架材料奠定理论与技术基础。

为满足工程化组织或器官的生成和塑形要求，在组织工程技术中，需提供良好的细胞支架，细胞支架的稳定性是决定其性能的重要指标。两性pH敏感凝胶作为一种常用的支架材料，当被植入生物体内时往往同时受力学场、浓度场和温度场的作用而发生屈曲、起皱等失稳行为。.本课题组针对两性pH敏感凝胶在多场耦合作用下的稳定性这一复杂、高度非线性问题开展研究，主要研究内容和结论如下：.（1）建立了能反映分子链缠结特征的两性pH敏感凝胶自由能函数。分子链缠结是高聚物的基本特征，基于slip-link缠结模型，利用勒让德变换建立了包含分子链缠结信息的两性pH敏感凝胶自由能模型；可以通过交联密度、不可伸展参数以及滑移参数等参数研究分子链缠结对两性pH敏感凝胶溶胀变形的影响。.（2）运用变分原理，结合两性pH敏感凝胶溶胀变形理论、铁木辛柯弹性稳定理论和冯卡门弹性非线性板理论，分别建立杆状和膜状两性pH敏感凝胶失稳判据。研究了不同链缠结状态、盐浓度和pH值条件下的杆状和膜状该类凝胶支架屈曲和起皱临界应力、临界细长比和临界波长；研究表明杆状和膜状该类凝胶支架的稳定性除了与材料参数、物理力学性质和几何尺寸有关外，杆的轴向载荷、膜的面内载荷以及基底的泊松比是决定其稳定性的重要因素。.（3）优化两性pH敏感凝胶溶胀变形模型，并成功将该模型植入ABAQUS中，实现对形状复杂三维凝胶支架失稳的模拟。该模型克服了已有模型只适用于酸性或碱性溶液的缺陷。通过与实验数据对比，验证了模型和有限元程序的正确性。基于此，解释了皮肤支架泡水起皱、蚕豆种皮的脱水收缩等屈曲失稳机理。.（4）考虑化学反应、离子迁移和双电层效应，建立了描述多场耦合作用下两性pH敏感大凝胶和微凝胶形变过程的瞬态分析模型，完成了ABAQUS用户子程序的编写，为分析凝胶支架失稳的演化奠定基础。.本课题组的研究确定了两性pH敏感凝胶支架失稳判据，给出了分析形状复杂支架失稳的有限元方法，揭示了该类支架失稳机理，对组织工程支架的设计和优化具有重要的理论和工程实际意义。