Study On Antitumor And Osteogenic Properties Of Additive Poly-L-Lactic Composite Bone Scaffold

The number of patients with bone defects caused by bone tumor resection is increasing.In order to avoid tumor recurrence and accelerate bone defect repair,it is urgent to develop artificial bone scaffolds with anti-tumor and bone regeneration functions.Poly-L-lactic acid（PLLA）is widely used in the preparation of artificial bone scaffolds due to its excellent biocompatibility,biodegradability and machinability.However,the lack of anti-tumor function and inability to regulate cell behavior limit its further application in bone defect repair.The construction of anti-tumor drug delivery system in the scaffold is expected to effectively kill tumor cells and endow the scaffold with long-term anti-tumor functions.In addition,the construction of endogenous magnetic microenvironment is conducive to mediating cell behavior and enhancing the osteogenic ability of scaffolds.In this thesis,ascorbic acid was loaded into Fe-doped mesoporous silica as a drug delivery system,which triggered Fenton reaction in acidic tumor environment.And the orientation assembly of Fe₃O₄nanoparticles was induced by external magnetic field to form magnetic nanochains.The magnetic stimulation was used to regulate cell behavior and enhance the osteogenic differentiation ability of scaffolds.The main work and conclusions of this thesis are listed as follows:1.Aiming at the difficult preparation of bone scaffolds with personalized shape and porous structure,selective laser sintering（SLS）technology was proposed to prepare PLLA bone scaffolds with three-dimensional structure.The effects of laser power,scanning speed and filling distance on the performance of PLLA scaffold were investigated.By analyzing the correlation mechanism between laser energy density and mechanical properties of the scaffold,the laser process parameters were further optimized.The optimal process parameter combination was obtained as laser power of 7 W,scanning speed of 100 mm/s and filling spacing of 0.24 mm.2.Aiming at the lack of anti-tumor function of PLLA scaffold,Fe-doped mesoporous silica loaded ascorbic acid drug delivery system was constructed（AA@Fe-SiO₂）,introducing it into PLLA scaffold by SLS technology.It was found that the scaffold had good acid-triggered degradation and AA release ability.The released Fe³⁺significantly promoted the oxidation process of AA.The concentration of hydrogen peroxide was increased by120.2%.Fluorescence probe staining and flow cytometry showed that scaffolds could generate a large number of hydroxyl radicals in tumor environment and induce late apoptosis of tumor cells.3.Aiming at the slow repair of bone defects caused by the inability of bone scaffolds to regulate cell behavior,Fe₃O₄nanoparticles were assembled into nanochains by external magnetic field induced,and then shaped by silica deposition to obtain Fe₃O₄@SiO₂magnetic nanochains.It was found that the introduction of Fe₃O₄@SiO₂nanochains endowed scaffolds with good magnetic properties.The magnetic stimulation significantly enhanced cell activity,induced mineralization,and promoted the expression of osteogenic related genes（runt-related transcription factor-2,osteopontin,osteocalcin and osterix）.