Study On 3D Printed PLLA-modified HA Scaffold Loaded With Methotrexate Microspheres And Its Properties

Osteosarcoma is a primary malignant tumor with genetic heterogeneity.At present,surgical resection of the lesion is the main treatment.Since there are many bone and tissue defects left after resection,how to repair and reconstruct bone tissue while treating osteosarcoma has become a research hotspot at home and abroad.In this paper,methotrexate,an antiosteosarcoma drug,was used as a model drug to prepare drug-carrying microspheres with slow and controlled release.By 3D printing,poly lactic acid for left-handed modified materials,hydroxyapatite as basal material,have certain mechanical properties was prepared,good biological safety,to promote bone growth and adjustable degradation rate of 3D porous scaffolds,and the carrier drug microsphere combined with composite porous scaffolds,the secondary structure of slow release can be targeted drug delivery is prepared,in order to delay the drug preliminary interpretation of the phenomenon,increase the utilization ratio and longer treatment time.Firstly,the MTX drug-loading microspheres were prepared by emulsifier volatilization method.The speed of magnetic stirrers,PVA concentration and temperature were taken as the influencing factors for the microspheres forming.Four factors and three levels of orthogonal test were designed.The results showed that the lower the speed of the magnetic agitator,the better the surface morphology of the microspheres,and the higher the loading rate and encapsulation rate.12 h before in vitro drug release,drug loading microspheres decreased by 18.78% compared with pure drug release,and at 120 h,drug loading microspheres decreased by 42.07% compared with pure drug release.Through drug release kinetics fitting,MTX drug loading microspheres complied with the drug release mechanism of PEPPAS biodegradable drug loading microspheres.Secondly,the composite porous bone scaffold was prepared by mixing PLLA and HA with good degradation performance through 3D printing extrusion molding equipment.The experimental results showed that the mechanical properties,hydrophilicity and degradation properties of the composite scaffold were enhanced with the increase of PLLA mass fraction.Compared with the minimum compressive strength of human cancellous bone,the compressive strength of the composite scaffold was increased by 2.27 times and Young’s modulus was increased by 32.67% when PLLA mass fraction was 50%.After 10 weeks of degradation,the degradation rate of the scaffold model was 29.98% higher than that of HA/PVA scaffold,and it met the biosafety evaluation standard and had good ossification.Finally,according to the results of the first two parts of the test,the 3D printer was used to prepare the surface modified bone scaffolds loaded with MTX drugs and MTX microspheres.The results showed that the pressure resistance of the three groups of scaffolds increased by 105.6%,141.2% and 227.6%,respectively,compared with that of the lowest cancellous bone.The weight loss rate of PLLA stent was 362.55% higher than that of HA/PVA stent,and the weight loss rate of micropellet stent was 49.13%higher than that of MTX stent.One day after drug release,the drug release rate of microsphere stent was 49.85% of that of MTX stent.After 12 weeks of drug release,the difference of drug release between microsphere stent and MTX stent was 5.35%.