A Research In Subcutaneous Heterotopic Ossification Of Tissue-engineered Cartilage And Its Prevention

Repair of cartilage defects has been a thorny issue in the field of surgical treatment.Tissue engineering technology is the effective means to solve the problem of cartilage defects.Bone marrow mesenchymal stem cells are important mesenchymal stem cells and one of the most promising seed cells.However,when the constructed tissue engineered cartilage is implanted into subcutaneous environment,it is prone to ossification.In bone development theory,VEGF-mediated vascularization is the key to ossification.Chondromodulin 1(CHM1)is an important vascular suppressor of cartilage secretion.Is the expression of CHM1 closely related to the subcutaneous vascularization and ossification of cartilage constructed by BMSC? Are vascularization factors such as VEGF associated with ossification of such cartilage in the subcutaneous environment?This study was performed using BMSC in CHM1 knockout mice(KO group).There was no difference in the basic characteristics of BMSCs between two kinds of mice.When in vitro tissue engineered cartilage was implanted into subcutaneous environment,KO group samples were more easily ossification,VEGF expression was higher.This suggests that CHM1 and VEGF are closely linked to subcutaneous ossification of such cartilage.Axitinib inhibits vascularization of tumor tissue by inhibiting the action of VEGF,preventing its growth and metastasis.Axitinib and electrospun membranes are made into sustained-release materials.Since chondrocytes tend to form more stable cartilage,thepresent study used chondrocytes to initially explore the relevant parameters of the sustained-release material.First,three kinds of drug-loaded electrospun membranes were made: control group(0%),low concentration group(1%)and high concentration group(5%).Through the analysis of material science,it shows that the electrospun film has better nanostructure and sustained release properties.Then by the sandwich method to make cell-material composite,it was implanted in nude mice subcutaneously after 8weeks.The results showed that the high concentration group can form a good cartilage tissue,effectively reduce the vascularization and ossification,and has good biosafety.In short,axitinib sustained-release electrospun membrane has good anti-ossification effect,the next step in-depth study.