Preparation Of 3D-printed Absorbable Sustained-release Microspheres And Their Sustained-release Properties

Objective: The biodegradable spherical β-TCP scaffold was prepared by light-curing 3D printing technology and loaded with VA-PPF/PLGA microspheres to obtain the drug-loaded composite VA-PPF/PLGA/β-TCP scaffold.The sustained drug release performance of the composite scaffold was evaluated by comparing with the VA loaded PMMA bone cement spheres.To provide a reference for the clinical exploration of a new drug sustained-release carrier.Methods: The β-TCP scaffold was prepared by 3D printing SLA(stereo-lithography).The morphology,porosity,shrinkage,expansion rate,mechanical properties,elemental analysis,and scanning electron microscopy were used to observe the adhesion and growth of MC3T3-E1 cells on the surface of the scaffold,and the biocompatibility of the scaffold was evaluated.VA-PPF/PLGA microspheres were prepared by double emulsion solvent evaporation method.The β-TCP scaffold and VA-PPF/PLGA microspheres suspension were mixed by shaking,and the microspheres were adsorbed into the micropores of the scaffold.Vancomycin and PMMA bone cement were evenly mixed at a ratio of 2g:40g,and a spherical shape similar to that of β-TCP scaffold was made by the mold method.The drug release of the composite scaffolds and VA-PMMA cement spheres at the same time points of 1,2,3,6,12,24,36,48 and 60 days was measured by ultraviolet spectrophotometer.Results: The 3D printed β-TCP lattice sphere scaffold was a white sphere and porous structure,with a diameter of about 6.5mm.The total porosity was about(78.3 ± 0.65)%,of which the microscopic porosity accounted for(21.1 ± 0.3)%,and the macroscopic porosity was(57.25 ± 0.35)%.Electron microscopy showed that the diameter of the trabeculae was 500 um,the pore size was 500 um,and the pores were uniform in size,arranged neatly,and connected to each other.By analyzing the expansion rate and contraction rate of the sintered scaffolds,the macroscopic pore size of the scaffolds was measured to be 540-610 μ m.The lower compressive strength of the QD structure scaffold was 3.2MPa,and the maximum compressive strength was 4.6 MPa.The maximum compressive strength of the OP structure was 8.7MPa.Scanning electron microscopy showed that the cells were well spread and spindle-shaped,and the number of cells increased with the increase of culture days.Elemental analysis showed that the scaffold was composed of calcium and phosphorus.The results of in vitro drug release experiment showed that there was a certain drug burst release phenomenon in the initial 1-3 days of drug release.The cumulative drug release rate of the drug-loaded PMMA sphere group was about(15.95±0.63)% in the first day,and was about(20.37±0.14)% in the third day.The cumulative drug release rate of the composite scaffold group was about(10.38±0.09)% on the first day,and about(13.90 ±0.23)% on the third day.The burst release of the composite scaffold was significantly weaker than that of the drug-loaded PMMA ball,and the difference was statistically significant(P<0.001).The cumulative drug release rate of loaded PMMA sphere was about(34.97±0.96)%,and the cumulative drug release rate of composite scaffold was about(29.74±1.36)%.The drug release of loaded PMMA sphere was slightly higher than that of composite scaffold,but from about 36 days,the drug was no longer released or released very little(P=0.90).The cumulative drug release rate of the composite scaffold group was(41.94±2.41)% at the 60 th day,and it could continue to release drugs to maintain the antibacterial effect for a long time.The cumulative drug release rate of the two groups gradually increased with the extension of time,and the cumulative drug release rate of the OP group was higher than that of the QD group on the60 th day(P<0.001),but both groups could continue to release drug and maintain the antibacterial effect for a long time.Conclusion: In summary,the total porosity of the two lattice spherical scaffolds was about(78.3 ±0.65)%,which was close to the porosity range of human cancellous bone(50.0～90.00)%.The mechanical properties of the two kinds of lattice scaffolds are within the range of compressive strength of cancellous bone(2～12)MPa,which can effectively avoid the stress shielding effect.The macroscopic pore size of the sintered lattice scaffolds is distributed between 540 μm and 610 μm,which is suitable for the proliferation of osteoblasts.The cell morphology under scanning electron microscope proved that the scaffold had good biocompatibility.The sustained drug release rate of the two composite scaffolds increased with the increase of drug release days.Compared with the antibiotic bone cement that is currently used in clinical practice,the composite scaffolds have better long-term drug release and long-term antibacterial effect.