Study On The Preparation Of A New Hybrid Nano-apatite And Its Composite With Poly (Lactic-co-glycolic Acid)

It is difficult to obtain ideal nano-hydroxyapatite/poly（lactide-co-glycolide）（n-HA/PLGA）composite used for bone materials,owing to the agglomerate of n-HA and the poor interface compatibility with PLGA.The common solution is surface grafting modification of n-HA particles,but this method has some defects.In recent years,a new method to modify n-HA is to prepare organic/inorganic hybrid nanoparticles.Based on this,in this paper,a novel hybrid nano-hydroxyapatite was achieved by introducing some biocompatible macromolecules（cyclodextrin（CDs）,carboxymethyl-β-cyclodextrin（CM-β-CD）and lignin）in the form of reactants during the preparation of n-HA,which is expected to be effectively compounded with PLGA,so as to obtain a composite with excellent mechanical properties,biodegradability and biological properties.Firstly,a novel co-hybridization nano-apatite was prepared by introducing different types cyclodextrins ofα-cyclodextrin（α-CD）,β-cyclodextrin（β-CD）orγ-cyclodextrin（γ-CD）and different Mg²⁺substitute contents of 5,10 and 20 mol%in the form of reactants.The results of FTIR,XRD,SEM,dispersibility and PBS immersion experiments showed that cyclodextrin and Mg²⁺were successfully incorporated in n-HA lattice,so that the crystallinity,cell parameters and crystallite sizes of CD-Mg-n-HA were remarkably decreased,and its dispersion in dicholomethane and solubility in PBS were also greatly improved in contrast with the traditional n-HA.In vitro cell experiments showed that CD-Mg-n-HA significantly enhanced cell adhesion and proliferation,and the higher the Mg²⁺content was,the higher the biological activity of the material was.Secondly,to obtain a nano-apatite with better dispersibility,amphiphilic macromolecule CM-β-CD was introduced as reactant during thesynthesisprocess ofn-HA,thehybridnano-apatite（CM-β-CD-HA（Co））was obtained by co-precipitation method.FTIR,XRD,XPS,TGA,TEM and dispersion experiments of CM-β-CD-HA（Co）were investigated,and compared with n-HA modified by blending method.The results showed that co-precipitation method was more conducive to graft more organic compounds on the n-HA surface and effectively improve the dispersion of n-HA in CH₂Cl₂.Then,CM-β-CD-HA（Co）was introduced into with PLGA,and the properties of CM-β-CD-HA/PLGAcompositeswerealsoinvestigatedby electromechanical universal tester,XRD,SEM,DSC and in vitro cell experiments.The results showed that(CM-β-CD-HA（Co）had better dispersibility and interfacial bonding in PLGA matrix,and its crystallinity and tensile strength were obviously improved.Especially,when 10 wt%CM-β-CD-HA（Co）was added,the tensile strength of the composite increased by 14.84%compared with the PLGA matrix,which reflected better mechanical reinforce effectiveness for PLGA.In vitro cell experiments also indicated that the material was non-cytotoxic and had good cell adhesion and proliferation ability.Thirdly,lignin,another amphiphilic biopolymer,was chosen to surface-modify n-HA through co-precipitation method or blending method,and the effects of adding different content,different reaction time and other reaction conditions were investigated by FTIR,XRD,TGA,TEM and the dispersibility experiments.The results stated that the n-HA surface-modified with lignin by co-precipitation method had better dispersibility in hydrophobic solvents,and the more amount of lignin and appropriate reaction time was beneficial for improving its dispersibility.The above surface-modified n-HA was combined with PLGA and characterized by a universal testing machine,SEM,DSC,POM,DMA and in vitro cell culture experiment,the results showed that the modified n-HA with good dispersibility had better dispersibility and interfacial bonding with PLGA matrix.When 10 wt%L-HA（0 h）was added,the tensile strength of PLGA was increased by 15.09%,and the composite displayed better cell adhesion and proliferation ability,suggesting lignin was not obvious cytotoxicity.Finally,hybrid nano-apatite was synthesized by introducing lignin combining CM-β-CD,and the effects of different introductory sequences of reactants on hybrid nano-apatite were investigated,and compared with the hybrid n-HA modified by CM-β-CD or lignin single.The results of FTIR,TEM,dispersion experiments and other characterization showed that the morphology of n-HA modified by co-modification（g1-HA）became spherical with higher grafting rate and displayed better dispersion.Moreover,one of the co-modified HA was compounded with PLGA,and the results of the universal testing machine,SEM,DSC,POM,in vitro degradation and cell experiments demonstrated that the dispersibility and interfacial bonding of g1-HA in PLGA matrix have been greatly improved.Even the addition amount of g1-HA was 15 wt%,the tensile strength of the material was still 14.53%higher than that of PLGA,which was significantly higher than the hybrid n-HA modified by CM-β-CD or lignin single.Additionally,there was no significant difference for degradation and cell activity,which proved that the combined hybrid modification method had a beneficial synergistic effect on the modification of n-HA.