Metal-Organic Frameworks Induced Biomineralization Enhanced In Situ Bone Defect Repair

OBJECTIVE: To investigate the mechanism of biomineralization induced by ZIF-8,a member of the metal-organic framework.To investigate the ability of ZIF-8 to induce the biomineralization of polycaprolactone(PCL)material which do not have the biomineralization ability;To prepare ZIF-8@PCL biological scaffolds with good bone conduction and osteo-induction properties,and to study the effects of ZIF-8@PCL promoting bone regeneration and repairing bone defects.METHOD:1.ZIF-8 with molar ratio of 8.75 was synthesized by "one-pot " method,and the material was characterized.ZIF-8 powder was soaked into simulated body fluid(SBF)in dialysis bags,and its biomineralization process was observed by transmission electron microscopy(TEM)and EDS-MAPPING energy spectrum scanning.2.The ZIF-8@PCL composite material with 10% ZIF-8 concentration was prepared by melt molding method.After mineralization in SBF,the formation of mineralized crystallization on the surface of the material was observed by SEM on the third and seventh day,and the biomineralization properties were evaluated.Bone marrow mesenchymal stem cells(BMSCs)were implanted on the surface of the material to observe the adhesion and proliferation of cells at the 3rd and 7th day,and the morphology of individual cells was evaluated at 3h and 12 h after implantation to evaluate the biological activity of ZIF-8@PCL composite material.3.The ZIF-8@PCL bone biological scaffold with a diameter of 5 mm and a thickness of 2 mm was printed using MEW technology,which was pre-mineralized in vitro and implanted into the rat model of skull defect.Bone regeneration was assessed by microCT one month after operation.H&E sections were stained to observe whether there were significant pathological changes in the main organs and to evaluate biocompatibility in vivo.RESULT:1.ZIF-8 can induce the uniform deposition of calcium and phosphorus ions in the crystal structure.With the increase of time,the formed mixed minerals agglomerate and become larger,and the crystal structure of ZIF-8 appears collapse.2.There is no significant difference between ZIF-8@PCL material and simple PCL material in general appearance,but it can be observed that the surface of the flake material is rougher by the scanning electron microscope.The mineralized ZIF-8@PCL material had obvious calcium and phosphorus crystal deposition on the surface,and showed higher cell inoculation rate and proliferation rate than PCL material alone.Micro-CT 3D reconstruction images showed that obvious mineralization points appeared in the ZIF-8@PCL material group,and the density was close to the bone density of normal people.3.The ZIF-8@PCL biological scaffold with porous structure prepared by MEW technology has a fiber diameter of about 150 μm,the pore diameter between the fibers is between 200 and 300 μm,and there is a position deviation between the upper and lower fibers.After mineralization in SBF,white calcium and phosphorus crystals were deposited on the surface of ZIF-8@PCL biological scaffolds.Over time,more and thicker crystals are deposited.The bone volume and relative bone volume of the ZIF-8@PCL biological scaffold group were more than two times higher than the quantitative data of the blank control group and PCL group,and the bone density was also higher than the other two groups.H&E staining showed no obvious pathological changes in the main organs of the rats.CONCLUSION:1.ZIF-8 material has the ability to induce biomineralization.2.ZIF-8 can induce the biomineralization of PCL material with high mineralization efficiency,and the mineralized ZIF-8@PCL material has good biocompatibility and bioactivity,which can promote cell adhesion and proliferation.3.ZIF-8@PCL biological scaffolds have the ability of bionic mineralization in vitro,and the mineralization efficiency is high;It has good biocompatibility in vivo and has obvious therapeutic effect of promoting bone defect repair.ZIF-8@PCL biomimetic mineralized biological scaffold printed by PCL materials has good biomimetic mineralization and osteogenic properties in vitro and in vivo,and can promote bone regeneration,showing great application potential in biomimetic bone substitute biomaterials.