Preparation Of Rare Earth Doped Magnetic Apatite Scaffold And Study On Its Bone Formation Performance

The repair of large area bone defect has brought great challenge to clinical,urgent to develop a new multi-functional bone repair biomaterial.The structure and composition of artificial organic/inorganic biomimetic scaffolds are similar to those of bone,but the bone inductivity is poor.Therefore,the preparation of artificial biomimetic scaffolds has good biocompatibility,osseoconductive and osteogenic scaffold materials are urgent.Hydroxyapatite/chitosan?HA/CS?scaffolds have good biocompatibility,bone conductivity and biological activity play an important role in cell adhesion,migration,proliferation and differentiation.Two kinds of magnetic porous composite scaffolds La-MHA/CS and Yb-MHA/CS were prepared by mineralizing and freeze-drying methods by doping rare earth?La or Yb?and magnetic SrFe₁₂O₁₉9 nanoparticles.The phase structure,microstructure,crystal form,thermal stability and magnetic properties of rare earth doped magnetic apatite composite scaffolds were studied by means of XRD,FTIR,SEM,TG-DTA and VSM.Cell experiments in vitro and animal experiments in vivo were carried out.The bone inductivity and bone properties of different rare earth doped magnetic scaffolds in vitro were analyzed.La-HA/CS and La-MHA/CS composite scaffolds were successfully prepared by mineralized drying technique and compared with pure HA/CS scaffolds.The two kinds of composite scaffolds have three-dimensional porous structure with pore size range of 100-300?m.The crystallinity of HA is lower,and the morphology is short rod shape with the length at 200-300 nm and the width at 80 nm,distributed in the hole wall of the scaffolds.The introduction of La and SrFe₁₂O₁₉9 did not change the three-dimensional pore structure and morphology of HA.The La-MHA/CS magnetic materials had good magnetic properties,and the coercive force was 3014 Oe,saturation magnetization is 4.19 emu/g,residual saturation magnetic field is 2.02emu/g.In vitro cell experiments showed that La-HA/CS and La-MHA/CS could promote cell proliferation and differentiation and promote the expression of BMP-2,ALP,OCN and RUNX-2 osteoblast-related genes.La-MHA/CS had the best effect on osteoblast differentiation.The effect of new bone regeneration in animal experiment:La-MHA/CS>La-HA/CS>HA/CS.The results showed that rare earth La³⁺could promote osteogenesis,and the effect of La and SrFe₁₂O₁₉9 magnetic nanoparticles on bone formation was more obvious.Yb-HA/CS and Yb-MHA/CS composite scaffolds were prepared by freeze-drying using chitosan as organic template and HA/CS scaffolds were used as control.The three-dimensional connecting pore size of the two kinds of scaffolds was distributed in 100-250?m,the length of short rod HA was about 250 nm and the width was about 80 nm.The two scaffolds were uniformly exposed to chitosan film.The coercive force of Yb-MHA/CS magnetic scaffolds was 3269 Oe,Saturation magnetization 3.48 emu/g,residual saturation 1.64 emu/g.In vitro cell experiment showed that Yb³⁺in Yb-HA/CS scaffolds can promote cell proliferation and osteogenic differentiation.Yb-MHA/CS contains Yb and magnetic SrFe₁₂O₁₉9 has better osteogenic effect.This effect is through activate Smad signaling pathway to make BMP-2,ALP,OCN and RUNX-2 osteogenesis-related genes upregulation can be confirmed.The model of skull defect in vivo showed that the effect of bone regeneration were Yb-MHA/CS>Yb-HA/CS>HA/CS.Rare earth elements?La or Yb?and magnetic SrFe₁₂O₁₉9 play an important role in enhancing the ability of bone induction of HA/CS.Rare earth doped magnetic apatite scaffolds have good biocompatibility,cell proliferation and bone induction ability.The effective reconstruction of bone defect makes La-MHA/CS and Yb-MHA/CS have great potential application value in orthopaedic implant materials.