Preparation Of Magnetically Responsive Nanocomposite And Its Regulation Mechanism Of Biodegradability And Bio-Performance

With the developments of science and technology,the application of bone tissue engineering in clinical treatment of bone diseases is gradually rising.One of the main aims of bone tissue engineering is to develop new implant materials for realizing the repair,reconstruction or functional replacement of injured bone tissue,which solves the clinical problems on the therapy of large bone defect and fracture.As a typical tissue engineering material,biodegradable polymers(polyester,et al.)have been studied systematically,but there are still many problems to be solved:1)lack of regulation of post-implantation degradation,its degradation rate can only be preset and adjusted by molecular weight,crystallinity of monomer ration of the polymer matrix and cannot be adjusted in real time according to the state of bone healing;2)lack of responsiveness to external environment and the ability to signal with surrounding tissue cells.Recently,magnetically responsive nanocomposites have been widely studied and applied in the field of biomedicine due to their unique physical and chemical properties.Among them,the excellent magnetocaloric effect of magnetic materials has been fully reflected in the treatment of tumor.On account of the obvious temperature dependence of degradation behavior of degradable polyester material,the magnetocaloric effect of magnetic biomaterials may be used to realize the real-time regulation of the degradation of bone implants.Therefore,it is of great significance to develop and explore the degradation behavior of polymer-based magnetic nanocomposites under magnetic stimulation.Additionally,studies have shown that the magnetic materials can effectively regulate cell behavior(such as promoting cell adhesion,migration and differentiation)and promote tissue regeneration under magnetic stimulation.However,the potential mechanism and the optimal design of magnetic materials still need to be further explored.Therefore,we design and synthesize magnetic nanoparticles with different surface properties,compounding with biodegradable polymer(poly(lactide-co-glycolide),PLGA)to form a series of novel nanocomposites with magnetic responsiveness.Furthermore,the regulatory effects and mechanism of the combination of magnetic nanocomposites and exogenous magnetic stimulation on material degradation and biological performance are systematically evaluated,as well as the potential application prospects in bone tissue engineering.The main achievements and innovations of this dissertation are as follows:1 Oleic acid modified iron oxide(IO-OA)nanoparticles were prepared by thermal stimulation could synergically enhance cell adhesion,proliferation,alkaline phosphatase decomposition method,and PLGA-based magnetic porous scaffolds were prepared by solvent casting/particulate leaching method.The degradation behavior and possible mechanism of the scaffolds under alternating magnetic field(AMF)were further investigated.The results indicate that the magnetocaloric effect of magnetic nanoparticles in AMF can effectively improve the degradation rate of scaffolds,and the IO-OA nanoparticles with better interface compatibility with PLGA matrix show higher magnetocaloric efficiency,so the effect of promoting scaffold degradation is more significant.Furthermore,the molecular dynamics simulations reveal that the enhanced motion correlation between nanoparticles with surface modification and polymer matrix can accelerate the energy transfer.In this work,the feasibility of magneto-controlled degradation of implants containing IO-OA is demonstrated,and an optimizing strategy for better heating efficiency of nanomaterials is provided.2 Aforementioned IO-OA nanoparticles were compounded with PLGA to prepare homogeneous nanomaterials with magnetic responsiveness.The biological effects and potential mechanism of the magnetic nanomaterials on MC3T3-E1 cells under static magnetic field(SMF)were investigated.In vitro cell experiments show that IO-OA/PLGA composites combined with magnetic activity,calcium deposition in extracellular matrix,and bone-associated gene expression in a dose-and time-dependent manner.Furthermore,in situ scanning by atomic force microscopy(AFM)captures the nano-deformation of magnetic substrate under SMF.Combined with the significantly upregulated expression level of the cellular force-related gene Piezo 1,it is speculated that the synergistic effect of magnetic composites and magnetic stimuli to promote osteogenic differentiation is attributed to the magnetically actuated nano-mechanical stimuli.3 In order to clarify the influence of surface and interface properties of magnetic nanomaterials on cell biological function and to obtain the optimal materials,the optimization design and validation of materials were carried out by the combination of calculation simulation and experiment.First of all,it is obtained from molecular dynamics simulations that the best mass fraction of surface grafted chains of nanoparticles is about 23.3%to generate the largest influence on surrounding polymer matrix when nanoparticles are subjected to constant traction.Then,experimental methods were used for demonstration.Iron oxide(IO)nanoparticles grafted with different amounts of poly(y-benzyl-L-glutamate)(PBLG)were prepared,which were compounded with PLGA to obtained magnetic nanocomposites.The effects of the magnetic composites on cell growth and osteogenic differentiation were further explored under SMF.In vitro cell experiments demonstrate that PBLG-g-IO/PLGA and magnetic stimuli can synergically activate Piezo 1 to increase intracellular calcium levels and promote osteogenic differentiation.And the best effect of promoting bone formation is achieved when the grafting amount of PBLG is 21.46 and 32.34%.The consistent conclusion of experiments and simulations indicates that 20-30%PBLG grafted on IO surface could make the cells receive the maximum mechanical stimuli from the magnetic materials,so as to achieve the best effect of bone repair.The feasibility of using simulation method to optimize the design of materials is also verified.The results of this dissertation indicate that magnetically responsive nanocomposites combined with magnetic stimuli have broad application prospects in the fields of bone tissue engineering and regenerative medicine.It not only can achieve magneto-controlled degradation to regulate the degradation behavior of implants in real time according to the state of bone healing,but also can produce magnetically actuated nano-mechanical stimuli to synergically promote osteogenic differentiation and accelerate bone repair.The surface properties of magnetic nanoparticles are closely related to magnetocaloric efficiency,magnetostriction degree and biological properties.And the research strategy combining experiment and simulation can shorten the research cycle of new materials and explore the potential application value of biomaterials.