BaTiO3/P(VDF-TrFE)纳米复合膜电-热耦合调控细胞力学响应和钙内流促进成骨研究

骨组织本征电、热等物理效应是生物材料仿生设计的重要途径，但现有研究多集中于单一物理特性设计，导致材料性能仍不能满足修复需求。电/热耦合设计是提升材料成骨性能的关键，其中材料电-热耦合效应协同调控成骨是核心科学问题。课题组前期发现调控材料表面电势可激活细胞力学感受和胞内钙离子差异性分布。因此，本项目提出材料电-热耦合调控细胞力学响应和钙内流协同促进成骨研究假设。通过构建BaTiO3/P(VDF-TrFE)铁电纳米复合膜，结合近红外热释电效应，调节填料维度、含量及光照等参数，实现电-热耦合性能可控。以细胞力学信号YAP分子和Ca2+信号为靶点，重点研究电-热耦合效应协同调控间充质干细胞成骨功能，解析细胞“跨膜力学响应-胞内钙信号转导-核内基因表达”级联反应分子机制，最后通过体内植入验证材料电热耦合效应促进成骨的有效性，为骨修复材料性能优化及其成骨调控原理解析提供科学依据。

Mimic the intrinsically electrical, thermal and other physical properties of bone tissue is an important approach for the bionic design of biomaterials. However, the researches are focused on a single physical property that can't meet the complicated clinical repair requirements of bone defects. How to make the materials with electrical-thermal coupling is crucial to improve bone repair effect, in which the electrical-thermal coupling effect regulating osteogenic differentiation is the key scientific problem. Our preliminary work displayed that the mechanoreceptor and the differential distribution of intracellular calcium could be regulated via surface potential. Therefore, this project hypothesizes that the electrical-thermal coupling effect could promote osteogenesis via cellular mechanical response and calcium influx. Based on the foundation of our previous work, the effects of the composition and structure of BaTiO3/P(VDF-TrFE) composite material on its electrical and thermal properties are studied in this study. The synergy relationship between electrical and thermal properties of the composite materials is explored to achieve the biomimetic coupling of multi-phase physical properties by adjusting near-infrared parameters, the composition, dimension and content of filler. The synergy effects of electrical and thermal properties on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were studied on cell, gene and protein level. This study focuses on the mechanical response and calcium influx to clarify the mechanism of dual-physical coupling on the process “transmembrane mechanical response- calcium signal transduction- expression of osteogenic genes in nucleus” of stem cells and to verify the effectiveness of electrical-thermal coupling on bone regeneration through implantation in vivo. This study will provide scientific basis to optimize novel bio-responsive bone repair materials and analyze the osteogenic mechanism.