Biodegradable Polymer Bone Implants Of Gd-based Micro/nanomaterials For Tracing And Their Biomedical Application

The current biodegradable polymer materials and their inorganic-organic composites,as orthopedic implants,can not be traced timely by existing medical imaging techniques after implantation.Because of the unique magnetic properties of gadolinium?Gd?compounds and the specificity of micro-nano materials?with surface effect and small size effect?,gadolinium containing micro-/nano particles and composites were prepared to study the feasibility as tracer in biodegradable macromolecule bone implant.Firstly,GdPO₄·H₂O,Gd₂O₃ and Gd₂O₂S micro-/nanoparticles were synthesized under solvothermal method and further calcination process.After incorprating into polylactic acid-glycolic acid copolymer?PLGA?,the MRI and CT imaging signals of composites were enhanced with the increase of gadolinium concentration.At the same gadolinium concentration,Gd₂O₃ MRI imaging signal was stronger than GdPO₄·H₂O and Gd₂O₂S,and CT imaging effect had no significant difference.The in vitro experiments showed that the gadolinium-containing nanomaterials at the proper concentration have good biocompatibility and can be screened for tracing biodegradable polymer bone implants.Secondly,GdPO₄·H₂O and GdPO₄ nanobundles were synthesized by solvothermal method and further calcination process The physical and chemical properties of the two products were analyzed in detailed.GdPO₄·H₂O and GdPO₄were chose to incorporate into the biodegradable bone implant of HA/PLGA due to the similar component of phosphate with hydroxyapatite?HA?.When its incorporation concentration was?0.2%?Gd/PLGA,w/w?,the signal of GdPO₄·H₂O/HA/PLGA implants could be traced clearly by MRI and CT.At the same gadolinium concentration,MRI imaging signal of GdPO₄·H₂O/HA/PLGA was significantly higher than that of GdPO₄/HA/PLGA,indicating that the uncalcined GdPO₄·H₂O was more suitable for tracing biodegradable polymers.The biological assessment results showed that when the composites were at low gadolinium concentration?0.8%,Gd/PLGA,w/w?,there was no obvious cytotoxicity and could promote the expression of osteocalcin and calcium mineralization to MC3T3-E1cells.The concentration decided by the above mentioned in vitro experiments were carried out for in vivo implantation experiments.After 0,2 and 8 weeks of observation,the changes of GdPO₄·H₂O/HA/PLGA bone implants and the growth status of new bone can be monitored simultaneously by MRI and CT.Moreover,there was no obvious inflammatory action in the bone defect and viscera when the concentration of gadolinium was 0.4%?Gd/PLGA,w/w?in GdPO₄·H₂O/HA/PLGA bone implants.Finally,in order to improve the dispersibility and biocompatibility of gadolinium-containing micro-/nanoparticles in the biodegradable polymer of PLGA,the polyglutamic acid modified product GdPO₄·H₂O-PBLG was synthesized when the feed ratio of GdPO₄·H₂O@SiO₂-APS:NCA was 1:0.25 with good dispersion and stability in the chloroform,and could mix with the biodegradable polymer materials uniform.Compared with the unmodified GdPO₄·H₂O,the MRI signal intensity of modified intermediates and products were significantly weakened.The results of in vitro experiments showed that the modified product of GdPO₄·H₂O-PBLG had good cell compatibility.In conclusion,the incorporation of gadolinium-based nanomaterials such as GdPO₄·H₂O to biodegradable polymers could not only achieve the traceability in vivo,but also improve the compatibility of biodegradable bone implanted materials.Further more,we also found that gadolinium-containing micro-/nanomaterials had potential applications in the induction of osteoblast differentiation and bone tissue regeneration.Although the surface modification of polyglutamic acid improved the dispersibility,stabilityandbiocompatibilityofgadolinium-based micro-/nanoparticles in the polymers,the traceability of the composites was decreased,so it needs to be further explored in the later research.