A Study On The Effect Of Scaffold Materials Stiffness On MDA-MB-231 Cell Biological Behaviors And BMSCs Osteogenic Differentiation

BackgroundIt is well recognized that cells are affected by various factors of the extracellular microenvironment.These factors include both biochemical factors,which have been widely researched previously,and also biophysical factors that play pivotal roles in cellular physiology by transmitting mechanotransduction signals into cells to regulate cellular behaviors,the cell differentiation,migration,adhesion and invasion.We prepared biomaterials/ECM with different stiffness,to mimic the different stiffness of extracellular matrix of body in physiological or pathological condition,which can be better understand how tumor cells and adult stem cells sense mechanical force and transmit transduction signals into chemical process or changes of gene expression to regulate cell behavior,differentiation or expression process in 3D microenvironment.ObjectiveBiomaterials and hydrogel systems with different stiffness were constructed to simulate the different stiffness of the in vivo environment.The effects of different ECM stiffness on tumor cell behaviors and adult stem cells osteogenic differentiation were studied.Methods1.Divalent metal ions with different concentration were used as crosslinking agents.Alginate and collagen I were used to fabricate interpenetrating networks(Interpenetrating Networks,IPNs)hydrogel with different stiffness to simulate the microenvironment of tumor cells.To explore the influence of the extracellular matrix with different stiffness on the migration,adhesion and invasion of tumor cells.2.PEG/SF/HAp scaffolds with different stiffness were synthesized to discuss the effect of ECM stiffness on osteogenic differentiation of adult stem cells.Results1.Interpenetrating networks(IPNs)hydrogel have independent of stiffness adjustment ability and is not affected by the ECM composition and the structure of the system.Based on PEG/SF/HAp scaffold with different stiffness,which is similar to natural bone ECM composition and arrangement of the porous structure.It has the characteristics of the aperture size uniform,good biomechanical performance,strong stability.2.Observation were obtained in IPNs with different stiffness,human breast cancer cells(MDA-MB-231)present different cell phenotypes and behaviors.By changing the arrangement and expression of microtubules and the population of extracellular vesicles secreted into the three-dimensional microenvironment by cells,breast cancer cells were affected throught the biological behaviors such as cell migration,adhesion and invasion.3.PEG/SF/HAp scaffold owns different stiffness and good biocompatibility,which support adult stem cell adhesion,diffusion,growth and proliferation.The scaffold is good to the osteogenic differentiation of adult stem cells under certain stiffness.ConclusionThe stiffness of extracellular matrix has a profound influence on the migration,adhesion and invasion of tumor cells and the differentiation of adult stem cells.