Study On Drug-loaded Polymer Composite Bone Tissue Engineering Scaffolds Based On Selective Laser Sintering

Additive manufacturing(AM)technology has been widely used in the preparation of tissue engineering scaffolds due to its excellent accuracy and speed of construction.However,in polymer-based AM manufacturing,the most widely used fused deposition manufacturing(FDM)technology usually requires the polymer to be processed under a processing temperature that exceeding the melting point of the polymer for a long time,which is easy to cause thermal decomposition of biologically active substances encapsulated in polymer substrates.Breaking through the bottleneck of AM manufacturing technology in tissue engineering scaffolds loaded with bioactive substances(hereinafter referred to as "bioactive scaffolds")will greatly promote the application of this technology in the field of tissue engineering.Selective laser sintering(Selective laser sintering,SLS)is an AM technology based on the fusion of powder particles by laser beam energy to form a solid structure.Its processing temperature can be below the melting point of the powder substrate.The heating history of the substance is short,so SLS may be an effective method to break through the bottleneck of preparation of bioactive polymer scaffolds.In this study,the AM laser processing equipment was first modified,and the equipment for AM processing was built based on the laser cutting equipment.The transformed laser processing equipment has a printing platform diameter of φ = 15 mm and a manually controlled Z-axis movement height accuracy of 0.02 mm.At the same time,a series of polylactic acid-bioactive glass-dexamethasone composite microspheres were prepared.The median particle size of the microspheres was between 115-120 μm and the drug loading range was 0.25-0.84 μg / mg.After processing by the above modification equipment,a series of drug-loaded porous scaffolds were successfully prepared,and the average pore diameter of the scaffolds was 450-500 μm.Analytical testing showed that the dexamethasone loaded in the scaffolds retained its biological activity after processing.The drug release test showed that the scaffolds could release the drug in a controlled manner,and the PBD-3 scaffold slowly released 69.2 ± 6.5% within four weeks.In vitro cell experiments showed that the drug-loaded scaffold group was superior to the unloaded drug control group in terms of cell proliferation.At the same time,the experimental group without exogenous drug cultivation in vitro also showed better in vitro bone formation-related marker expression.Animal experiments on rat skull defects show that the bone repair performance of the drug-loaded scaffold group is significantly better than that of the drug-free control group.The PBD-3 scaffold showed anew bone volume proportion of about 25.1% after 8 weeks of implantation.At the same time,the SLS processing of self-emulsifying polyurethane-inorganic material-dexamethasone composite microspheres was also carried out by the modified equipment.The dexamethasone-loaded polyurethane microspheres and composite microspheres composited with bioactive glass and hydroxyapatite,respectively,were prepared by using the characteristics of lysine chain extension self-emulsification.SLS was used to process the microspheres into 3d porous scaffolds.The drug release test of the obtained scaffolds showed that 41.5 ± 2.9 % of the initial test bursts occurred in the first 24 hours,and a total of 87.3 ± 6.2 % was released within 10 days.The scaffolds have good biological activity,and the introduction of BG and HA particles improves the biological activity of the scaffolds.The study confirmed the feasibility of using SLS to prepare drug-loaded composite polyurethane bone tissue scaffolds.The preparation of self-healing polyurethane scaffolds based on laser cutting was also studied.Self-healing polyurethane(Self-healing polyurethane,sh PU)based on disulfide bond was synthesized successfully with 4,4 ’-diaminodiphenyl disulfide as chain extender.The laser cutting machine was used to cut the sh PU film into the two-dimensional slicing material of the scaffold,and the scaffold was obtained after layer upon layer.The scaffold has a three dimensional porous structure of fiber interconnect and a good adhesion between two dimensional slices.The results show that this method is feasible to prepare tissue engineering scaffolds,and it has a good potential in the field of tissue engineering.