Fabrication Of Layered Double Hydroxide Coating On Mg Alloy And Its Application In Treatment Of Osteosarcoma

Osteosarcoma is the most common malignant bone tumor in children and adolescents,causing high mortality or disability rate of patients and great harm to the community and family.Currently,the clinically used standardized treatment schedule includes neoadjuvant chemotherapy+limb slavage surgery+postoperative adjuvant chemotherapy,but the overall survival rate of patients has not been further improved in the past 5 years,mainly due to postoperative local recurrence and metastasis of tumor.At present,the materials used in limb salvage therapy are mainly titanium alloy,stainless steel or cobalt-chromium-molybdenum(Co-Cr-Mo)alloy,all of which are inert and have no help to osteosarcoma treatment,and the loosens and ruptures rate of implant material is high due to mechanical mismatching with nature bone after implantation in the long term.Implant materials are in direct contact with focus lesion,thus can be used as the first front in the anti-tumor process.Therefore,the anti-tumor effect of implant materials is a potential mean to improve the treatment efficacy of osteosarcoma.Magnesium alloy is a representative of degradable metals and is known as the next generation of biomedical metal materials.It has good mechanical properties and degradability,and the magnesium ions produced by its degradation can effectively promote the formation of new bone.Recent studies have shown that magnesium alloy has good anti-tumor effect,so it also has great potential in the treatment of osteosarcoma.However,there are still many dissatisfactory shortcomings.Firstly,the degradation rate of magnesium alloy is too fast,which produces a large amount of magnesium ions and hydrogen,leading to the alkaline microenvironment around the focus lesion and will causing inflammatory reaction.Secondly,its anti-tumor effect is stronger than inert materials such as titanium alloy,but it is still not strong enough in the treatment of malignant tumors.Therefore,in order to meet the clinical application needs,it is necessary to improve the anti-corrosion effect and enhance the anti-tumor effect.To solve these two problems,this study in situ constructed Mg-Al double hydroxide(LDH)coating in the magnesium alloy surface by means of hydrothermal method,and load anion drug celastrol taking advantage of the substitution effect between LDH layer.The mainly results of this study includes:1,the magnesium alloy coating on the surface of LDH can significantly improve the corrosion resistance effect and biological compatibility of magnesium alloy,results of in vivo and in vitro research shown that the effect of osteogenesis and angiogenesis also improved;2,celastrol can slowly released from the LDH coating magnesium alloy after load into the LDH layer,and the experiments shown that the celastrol loaded LDH material can effectively kill osteosarcoma cells,inducing tumor cell apoptosis and reactive oxide species production.We further investigated the role of autophagy in celastrol loaded LDH material induced osteosarcoma cell apoptosis,and found that the apoptosis rate of tumor cell would increased when inhibit autophage,on the contray the apoptosis rate of tumor cell would decreased when activated autophage,thus reveal that autophage plays a antagonism role in celastrol loaded LDH material induced osteosarcoma cell apoptosis;3.In vivo experiments showed that celastrol loaded LDH material could significantly promote the formation of new bone at the early stage,which was conducive to the early stable binding of the material to bone,which might be related to the inhibition of osteoclast activity after the release of celastrol in bone environment.In conclusion,in this study,magnesium alloy was used as the substrate material to construct LDH coating and loaded with celastrol.The constructed new material can effectively kill osteosarcoma cells and promote bone repair,which proposed a new treatment method of osteosarcoma from the perspective of implant material.