P(VDF-TrFE)/BaTiO3纳米纤维复合材料的制备及其成骨性能调控研究

In view of the important scientific issue that the implanted materials’ microenvironment could regulate the function and differentiation of the host cells during the process of implantation for repairing the bone defects,, The purpose of this project is to design and prepare P(VDF-TrFE)/BaTiO3 piezoelectric composite materials with different component proportion, structure properties based on the piezoelectric effect of natural bone tissue. Establish the relationship among the composition, structure and electrical characteristics of the composite materials by regulating the diameter and aspect ratio of the BaTiO3 nanofibers. The biological behaviour of BMSCs response to the composite materials’ piezoelectric properties will be investigated systematically. This study focuses on the osteogenic differentiation related signal pathway like Wnt/β-catenin, MAPK, TGF-β/BMPs and so forth. Clarify the correlation between the materials characteristics and osteogenic differentiation of BMSCs. This project will provide the experimental foundation for the further optimized design, develop and application of the neotype and biologically responsible bone replacement materials.

针对材料在进行植入修复骨缺损过程中其材料微环境对宿主细胞功能与分化的调控这一重要科学问题，本项目基于骨组织的天然压电效应，仿生设计并构建具有不同组分比例、结构特性的P(VDF-TrFE)/BaTiO3纳米纤维复合材料体系，通过调节BaTiO3纳米纤维填料的直径和长径比，建立该材料体系组成、结构及力学性能与其电学特性的规律性关系。从细胞水平、基因水平和蛋白水平系统研究该复合材料特性对骨髓间充质干细胞（BMSCs）生物学行为的调控，以成骨分化过程中Wnt/β-catenin、MAPK和TGF-β/BMPs等相关信号通路为重点，探讨压电纳米纤维复合材料特性与BMSCs成骨功能分化之间的相互关联性，为新型生物反应性骨修复材料的进一步优化设计、开发与合理应用提供理论基础。

针对材料微环境调控细胞行为和组织再生这一重要科学问题，依据骨组织生长所依赖的电学环境，本项目系统研究了压电陶瓷BaTiO3基纳米复合材料体系的电学特性、结构特性以及力学特性对骨髓间充质干细胞（BMSCs）粘附、铺展、迁移以及成骨分化等生物学行为的影响，建立了材料组分、结构特性、力学性能与其电学性能间的规律性关系。初步证实了材料介导的仿生电学微环境对促进BMSCs粘附、铺展和迁移并诱导其成骨分化的有效性，显著提升骨缺损修复效果，主要发现了异质性电学微环境可能通过激活Hippo通路诱导Integrin表达来促进BMSCs成骨分化和骨再生，实现基于铁电效应的电活性骨修复材料“原位电刺激促进骨再生”的可调控，将为今后生物响应性植入材料的性能优化、产品升级以及临床效果提升提供理论指导。以上研究成果共发表SCI论文6篇（IF＞10有2篇），申请国家发明专利5项，获授权1项，指导博士、硕士研究生共5名。