Reseach On The Strategy And Mechanism Of Bone Defect Repair Based On Osteogenic Micro-tissue And OsECM

Bone tissue engineering is considered to be the best solution for large bone defects.However,the current classical bone tissue engineering repair strategy has some problems,such as complex process,low utilization rate of cells,uneven tissue construction and so on.In this study,based on the construction of osteogenic micro-tissue,we proposed an in situ bone tissue engineering repair strategy based on osteogenic micro-tissue.This strategy directly utilizes the osteogenic microtissue constructed in vitro as the scaffold material of "reinforcing steel bar",and directly implant it into the defect site in vivo to repair the bone defect.In this study,we designed experiments to compare the in situ bone defect repair strategy based on osteogenic micro-tissue with the classic massive tissue engineering bone repair strategy and the classic injection tissue engineering bone repair strategy based on digested cells.Through comparison,we confirmed that the in situ bone defect repair strategy based on osteogenic micro-tissue can effectively repair large bone defects.The process is simpler,more osteogenic cells are implanted in vivo,the utilization rate of cells can be obviously improved,meanwhile,the osteogenesis is more uniform,and the method is superior to the classic massive tissue engineering bone repair strategy;Compared with the classical injection-type tissue engineering bone repair strategy based on digestive cells,we found that the in-situ bone defect repair strategy based on osteogenic micro-tissue avoids enzyme treatment,retains more extracellular matrix,thus retaining the effective components in the extracellular matrix,and provides a more suitable microenvironment for the osteogenic cells implanted in vivo,thus also having a better repair effect.In addition,in order to verify the effective effect of extracellular matrix,we designed experiments to extract extracellular matrix composite gel matrix from osteogenic micro-tissue,and then compared the effect of skull repair with osteogenic micro-tissue,simple enzymatically digested cells,simple extracellular matrix and the complex of enzymatically digested cells and extracellular matrix.The results show that the gel prepared by the extracellular matrix can effectively promote the osteogenic repair of enzymatically digested cells,and achieve the bone repair effect almost equivalent to that of osteogenic micro-tissue.Therefore,it is confirmed that extracellular matrix can provide better microenvironment for transplanted cells in vivo,which is helpful to repair bone defects.However,in vitro,when observed the effect of extracellular matrix derived bone marrow mesenchymal stem cells on BMSCs,we found that extracellular matrix could not directly promote the osteogenic differentiation of the BMSCs,but had the function of inhibiting their proliferation,inhibiting their osteogenic differentiation and maintaining the stemness of cells.The interaction between extracellular matrix and cells and the role of this interaction in the whole process of osteogenic repair is far more complicated than we thought.There are more questions waiting for us to answer.There are more directions to explore.