磁场调控仿生磁电材料(BaTiO3/CoFe2O4)/P(VDF-TrFE)的成骨性能研究

To improve the osteogenesis and imitate the dynamic physiological magnetoelectric microenvironment of nature bone growth, we are developing a remote magnetoelectric biomimetic material. Based on our previous research about piezoelectric materials, we found the electricity of piezoelectric materials cannot be recharged to imitate dynamic physiological environment. In this research, we are developing the (BaTiO3/CoFe2O4)/P(VDF-TrFE) core-shell magnetoelectric nanocomposite which can be controlled by magnetic field and adapt the dynamic microenvironment of bone growth. Combining the ferroelectric and ferromagnetic properties of the BaTiO3/CoFe2O4 will lead to the magnetoelectric coupling effect. BaTiO3/CoFe2O4 will be added in the P(VDF-TrFE) with ideal biocompatibility to form the composite membrane. After electric polarization, the composite membrane will possess magnetoelectric properties. Controlling by magnetic field, the (BaTiO3/CoFe2O4)/P(VDF-TrFE) nanocomposite could imitate dynamic magnetoelectrics macroenvironment which can make up the defects of the piezoelectric materials. The (BaTiO3/CoFe2O4)/P(VDF-TrFE) nanocomposite is supposed to “feel” the magnetic field and improve the bone growth by imitate the microenvironment. In this research, we are planning to prepare the (BaTiO3/CoFe2O4)/P(VDF-TrFE) nanocomposite and culture the BMSCs which will be used to investigate osteogenic genes、proteins、 Wnt/β-catenin and TGF-β/BMPs signal pathways. The in vivo cranial defect rat models study will also be carried for the further verification. From the view of 4 dimension of the dynamic microenvrioment, this study might indicate a new way to develop the controllable biomimetic megnetoelectrics material for bone regeneration and reparations.

骨组织的生长是在动态的生理磁电微环境中进行的。模拟天然骨所处的动态磁电微环境，将更有利于促进骨再生。我们前期的研究中，发现压电材料仿生电位可促进成骨。但是压电材料不能提供磁环境并且其电学性能会逐渐衰减，不能提供仿生生理动态磁电微环境。因此本研究提出一种可通过体外磁场调控(非接触)的磁电仿生材料: (BaTiO3/CoFe2O4)/P(VDF-TrFE)核壳纳米复合物。该材料可仿生提供的动态磁电微环境。通过复合CoFe2O4的磁致伸缩性能与BaTiO3的压电性能产生磁电耦合效应，使该材料的磁电性能可被动态调控，通过受外加磁场的调控进行充电加磁，进而模拟骨周围的动态磁电微环境。通过体外BMSCs培养和大鼠体内实验，进一步研究该材料对骨形成相关基因、蛋白表达、Wnt/β-c等信号通路以及骨组织修复的影响。从动态骨修复的角度，为仿生磁电骨修复材料的研究、设计、开发提供新的思路。

仿生材料的研究与应用已经成为骨组织工程领域与骨再生医学领域的焦点之一。目前人工修复材料在结构上可以模拟骨的纳米结构，但是并不能很好的模拟生理状态下的骨组织所处的微环境提供的磁电刺激等生理刺激促进骨生长和重建。骨组织的生长是在动态的生理磁电微环境中进行的。模拟天然骨所处的动态磁电微环境，将更有利于促进骨再生。因此本研究制备出可通过体外磁场调控(非接触)的磁电仿生材料: (BaTiO3/CoFe2O4)/P(VDF-TrFE)核壳纳米复合物。该材料可仿生提供的动态磁电微环境。通过受外加磁场的调控进行充电加磁，进而模拟骨周围的动态磁电微环境。通过前期对压电材料P(VDF-TrFE)与磁电材料(CoFe2O4)/P(VDF-TrFE)的研究，针对通过体外BMSCs培养和大鼠体内实验，得到了最适电势以及最佳的磁颗粒填料比例，并得到最佳的磁电耦合系数(a)。应用筛选得到的磁电材料进行促进骨组织再生研究。体外试验中，进一步研究磁电材料对骨形成相关基因、蛋白表达、Wnt/β-c等信号通路以及骨组织修复的影响，发现10%组分的磁电材料促进成骨相关的基因以及蛋白的表达。体内实验验证了磁电材料在外加磁场的调控下具有良好的骨修复作用。本项目研究为仿生磁电骨修复材料的设计、制备提供新的思路。并有望为临床骨缺损的修复与治疗提供新的治疗方法。