Properties Of Porous Calcium Phosphate Bioceramic Microspheres Prepared By Combination Of Extrution Spheronization And Porogen

Calcium phosphate bioceramic particles have been widely applied in the field of bone repair materials because their composition is similar to the inorganic components of natural bone,and they can be adapted to fill bone defects of different shapes.The spherical calcium phosphate bioceramic particles can reduce the inflammatory reaction and tissue damage that the irregular particles are likely to cause.Among the whole methods of preparing spherical particles,the extrusion spheronization method has the advantages of uniform diameter and high productivity.In this study,calcium phosphate bioceramic microspheres were prepared by the extrusion spheronization method,and their properties were optimized through porogen and surface modification.The effects of the content of excipient,the diameter and volume of porogen,the surface coating modification and the content of coating on the physicochemical and biological properties of calcium phosphate bioceramic microspheres were studied.Calcium phosphate bioceramic microspheres were prepared by the extrusion spheronization method,and the effect of the content of the excipient microcrystalline cellulose(MCC)as the critical factor on the properties of microspheres were studied.As the amount of MCC added increases from 25 wt.% at intervals of 15 wt.% to 70 wt.%,the sintered ceramic microspheres had more obvious porous characteristics,higher open porosity,greater shrinkage,lower compression strength and more obvious degradation.The m BMSCs on the surface of calcium phosphate bioceramic microspheres had good adhesion,proliferation and ALP activity.The cells on the surface of microspheres with 40 wt.% of MCC had the best comprehensive ability of proliferation and osteogenic differentiation.The internal structure of microspheres directly prepared by extrusion spheronization method was still relatively dense.Therefore,the extrusion spheronization method and the porogen method were combined to prepare porous microspheres,and the effect of porogen diameter(20,40 and 100 μm)and porogen volume(45,60 and 75 vol.%)on the physicochemical and biological properties of microspheres were studied.With the increase of the porogen volume,the bioceramic microspheres of each porogen size showed a trend of increased micropores,increased shrinkage,increased degradation,and decreased compressive strength.The m BMSCs proliferated fastest on the surface of the non-porogen bioceramic microspheres and entered the early osteogenic differentiation stage faster.But at 7 days the number of cells on the surface of the porogen bioceramic microspheres was close to that of the non-porogen group.At 10 days,the porogen bioceramic microspheres are more conducive to the middle and late stages of osteogenic differentiation of cells to obtain mature osteoblasts.Utilizing the nature of the extrusion spheronization method,this method was further combined with the porogen method and the surface modification process together to prepare porous calcium phosphate bioceramic microspheres coated with magnesium phosphate.The effects of different coating amounts(2.5,5,and 10 wt.%)on the physicochemical properties and biological properties were studied.Magnesium phosphate was successfully coated on the surface of porous calcium phosphate bioceramic microspheres as its microstructure was dense.The microspheres with the largest coating amount had the highest shrinkage rate and the lowest porosity.Degradation of the bioceramic microspheres increased with the increase of the coating amount.The m BMSCs on the surface of the modified microspheres had better proliferation ability than the uncoated microspheres,and the largest coating amount microspheres had the highest ALP activity and genes expression related to osteogenic differentiation.The most significant HUVECs proliferation belonged to the microsphere with a coating amount of 5 wt.%.With the increase of the coating amount,the in vitro vascular formation ability of the microspheres increased,and they were all better than that of the uncoated group.The highest angiogenesis-related gene expression of the microspheres belonged to the microspheres with the largest coating amount.To sum up,the modified porous calcium phosphate bioceramic microspheres coated with magnesium phosphate had bone-forming and vascular-forming effects.