形状记忆聚氨酯回复应变与微纳结构的动态变化及其生物学效应研究

Shape memory polyurethane (SMPU) has attracted extensive attentions in biomedical fields, especially in micro-/non- invasive implants due to its good biocompatibility and shape memory effect. However, few attentions have been paid to its recovery strain during shape recovering and the resulting mechanobiological effects. In addition, it is proved that the thermodynamic incompatibility between the soft and hard segments of SMPU may promote the aggregation of hard segments to form micro/nano structures. Recovering process may change the micro/nano structures and further regulate cell responses, which, unfortunately, has been excluded from previous studies. This project will investigate the dynamic changes of recovery strain and micro/nano structures during shape recovery and their biological effects, with a final goal to get an in-depth and comprehensive understanding on the biocompatibility mechanism of SMPU. To realize this goal, the magnitude, rate and duration of recovery strain, and the shape, size and orientation of micro/nano structures during shape recovery in both air and PBS medium are first investigated, and the underlying mechanism is clarified by probing hydrogen bond assembly, recovery stress and stress relaxation; thereafter, the biological effects, including cell morphology, alignment, and cell fate are further examined by using mesenchymal stem cell (MSC) as model cells; the obtained results are finally integrated to form the biocompatibility mechanism of SMPU. The success of this project will expand the scope of biomechanics and biomaterials science, provide an effective guidance for SMPU design and fabrication, and further facilitate or even find new applications of SMPU in biomedical fields.

形状记忆聚氨酯（SMPU）因其良好的生物相容性和形状记忆效应而在无创/微创植入等医学领域备受关注，但鲜有研究关注其形状回复时的回复应变及力生物学效应。另外，SMPU软硬段间的热力学不相容会促使硬段聚集形成微纳结构。但鲜有研究关注回复过程对微纳结构及其细胞行为的影响。本课题拟创新性地研究SMPU回复应变与微纳结构的动态变化及其生物学效应，以期更深入全面地理解SMPU生物相容性机制。研究思路是：先系统研究SMPU在空气和PBS中回复时其应变（幅度、速率、时间）与微纳结构（形状、大小、取向）的动态变化规律，并从氢键组装、回复应力及应力松弛等角度解析动态变化的化学物理机制；再以间充质干细胞为模型细胞考查动态变化对细胞形态、取向和分化等的影响；最后解析SMPU生物相容性机制。本课题的成功实施将极大地丰富生物力学和生物材料的研究内容，对指导SMPU设计与加工，促进并拓展其医学应用有重要意义。

形状记忆聚氨酯（SMPU）因其良好的生物相容性和形状记忆效应而在无创/微创植入等医学领域备受关注，但鲜有研究关注其形状回复过程中应变与微纳结构的动态变化规律及其化学物理机制和生物学效应，更缺乏以回复应变与微纳结构为基础的SMPU生物相容性机制的阐释。本项目首先设计合成了一种玻璃化转变温度在37℃左右的哌嗪基形状记忆聚氨酯（PPZ-SMPU），利用FTIR、XRD和AFM等传统方法对PPZ-SMPU膜在形状回复过程中的相分离微纳结构进行了表征。针对传统方法在表征SMPU膜微纳结构时存在不可视和定量分析难的缺陷，本项目进一步设计合成了以噻唑吡啶二酸（TPA）为扩链剂的本体荧光聚氨酯（IFPU），实现了对SMPU形状记忆循环中微纳结构动态变化的荧光可视化观察和半定量计算。在回复应变定量检测方面，本项目分别利用DMA和视频检测的方法定量检测了SMPU在空气和DMEM 培养基中回复应变的变化规律，发现回复初期的应变速率较大，回复应变幅度随拉伸率升高而增大，SMPU膜在空气中的回复速率快于在DMEM溶液中的回复速率。为了进一步探究SMPU膜回复应变与微纳结构动态变化的化学与物理机制，本项目探究了回复过程中硬段间的氢键以及水与氨酯键/脲基间的氢键的动态变化，发现水可与SMPU软段发生氢键作用而与硬段间无明显的氢键作用，水对拉伸诱导的SMPU膜中硬段排列的有序性也无显著影响。进一步地探究回复应变和HS微纳结构对蛋白吸附和成骨细胞的影响，发现HS微纳结构通过调控蛋白吸附并与回复应变协同调控成骨细胞的生物相容性，包括在形状回复初期调控细胞取向，回复后期促进细胞增殖。本课题的成功实施极大地丰富了生物力学和生物材料学的研究内容，对指导SMPU设计与合成，促进并拓展其医学应用有重要意义。