Preparation And Properties Of Anti-tumor Bone Repair Materials

Osteosarcoma accounts for 20% of primary malignant bone tumors in the world.At present,comprehensive treatment is adopted for patients with osteosarcoma on the basis of preoperative and postoperative chemotherapy and surgical treatment.Although the treatment results are better than in the past,in recent years,osteosarcoma has encountered bottlenecks in clinical treatment,especially for patients with lung metastasis and chemotherapy resistance.Drug treatment of these patients requires the development of new and effective drugs and innovative treatment strategies.At present,surgical treatment is the main treatment of osteosarcoma,supplemented by comprehensive treatment of chemotherapeutic drugs.Surgical resection of tumor lesions can easily lead to bone defects.The destruction of bone tissue results in loss of motor function,local inflammation,infection and nerve injury.Incomplete marginal resection will also lead to recurrence and metastasis of residual tumor tissue.Therefore,the development of multi-functional bone repair materials with good bone tissue regeneration and tumor treatment has become a research hotspot in this field.Calcium phosphate cement(CPC)has the advantages of good plasticity,bone induction and bone conductivity.CPC can be used not only as a bone repair material to fill the defect,but also as a sustained release carrier of antineoplastic drugs.In this paper,a kind of calcium phosphate cement loaded with drug was prepared.Based on the study of calcium phosphate cement with good injectability and compressive strength,Tween 20 was added to the liquid phase to promote the solubility of curcumin.The sustained release system of curcumin-adriamycin hydrochloride-chitosan/hydroxyapatite bone cement was prepared by the combination of curcumin and doxorubicin hydrochloride.The main results of this paper are as follows:(1)Preparation of Cur-CS/HA bone cement(Grou p0,Group1,Group5 and Group10)with CS/HA,Mg O and Cur as solid phase and Tween 20 and 20% citric acid solution with different contents(0%,1%,5% and 10%,respectively)as liquid phase.The results showed that Cur-CS/HA bone cement had good injectability and the curing time was between 19-25 min.When the content of Tween 20 increased,the water absorption of cur CS/HA also increased.As the content of Tween 20 increased from 0% to 10%,the water absorption rate of HA bone cement increased from 17.27% to 43.41%.The test results of mechanical properties showed that the increase of Tween 20 content led to the decrease of compressive strength of bone cement.The compressive strength of Group0,Group1,Group5 and Group10 were 14.42 ±0.54,13.03 ±1.20,10.64 ±0.59,10.32 ±0.54 MPa respectively.(2)The results of sustained release test in vitro showed that Tween 20 could effectively improve the solubility of curcumin.The cumulative release rate of curcumin increased from5.50% to 10.60% as the content of Tween 20 increased from 0% to 10%.The results of MTT test showed that Cur-CS/HA could inhibit the growth of MG63 human osteosarcoma cells.Among them,the inhibition rate of Group10 was the highest,reaching 79.15%.The inhibition was enhanced with the increase of culture time and extract concentration.(3)Based on the formula of Group10,adriamycin hydrochloride was added to prepare Cur-ADM-CS/HA.SEM results showed that there were irregular flake crystals in the Cur-ADM-CS/HA material.The compressive strength tested by electronic universal testing machine showed that the compressive strength of bone cement decreased with the addition of Cur and ADM.(4)The results of in vitro sustained release test showed that Cur-ADM-CS/HA had good sustained release behavior.The extract of Cur-ADM-CS/HA material(50 mg/m L,10mg/m L,5 mg/m L,2.5 mg/m)was co-cultured with osteosarcoma cells,the treatment of MG63 cells with 50 mg/ml Cur-ADM-CS/HA extract had a significant inhibitory effect.On the 7th day,the inhibition rate of MG63 cells was 82.11%.Osteoblasts were co-cultured with Cur-ADM-CS/HA for 1 d,3 d,5 d and 7 d.Alkaline phosphatase activity and protein content were measured.The results showed that the AKP activity and protein content of Cur-ADM-CS/HA group were significantly higher than those of CS/HA group.AKP activity and protein content increased with the extension of co-culture time.The results show that the Cur-ADM-CS/HA constructed in this paper has good application potential in the field of bone tissue engineering.