Construction And Application Of Plug-in Dynamic Cell Culture Device

The blood-brain barrier(BBB)is a physiological barrier formed by brain microvascular endothelial cells and perivascular nerve cells.The BBB maintains the basic homeostasis of the internal environment of the brain tissue by regulating the transport of necessary nutrients and inhibiting the entry of harmful molecules in the blood into the brain,which is of great significance for maintaining the normal physiological function of the central nervous system.Current research shows that some neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis,are associated with disruption of the integrity of the BBB.In addition,the barrier function of the BBB prevents the penetration and effective entry of drugs for neurodegenerative diseases into the brain tissue,thus becoming an important challenge in the development of drugs related to neurodegenerative diseases.Existing BBB in vitro model studies mostly focus on developing high-level biomimetic porous permeable membranes and constructing complex spatial arrangements of cells.However,the reproducibility,ease of operation,and compatibility for different research needs of these models in experiments have been neglected.Therefore,they have been unable to replace the traditional Transwell barrier model.However,the static properties of the Transwell culture system are far from the dynamic blood flow microenvironment of the BBB in vivo,and it is not an ideal in vitro BBB model.Aiming at the above problems,this paper designs and manufactures a plug-in bionic BBB dynamic culture device.Using the means of hydrodynamic modeling,the simulation optimizes the optimal physiological shear force exerted by the fluid on the BBB vascular endothelial cells.The cerebral vascular endothelial cells(b End.3)seeded on the plug-in patch formed endothelial dense junctions with good barrier function under the stimulation of fluid shear force.Finally,a preliminary study on the deposition of soluble Aβ oligomers on the surface of BBB endothelial cells was carried out using the constructed plug-in dynamic BBB model.The results show that the plug-in dynamic cell culture system constructed in this study has good compatibility,simple operation and low cost.A dynamic BBB in vitro model with good physiological functions can be quickly established according to research needs.The model system was used to simulate the flow velocity of simulated healthy blood vessels and aging blood vessels,and preliminarily observed and obtained the deposition of soluble Aβ oligomers on vascular endothelial cells in two different physiological states.The feasibility of this model in neurodegenerative disease research was verified,and a solid foundation was laid for subsequent related mechanism research.