| The bone marrow(BM)is the predominate location for adult hematopoiesis which exists in three-dimensional(3D)porous cancellous bone cavities with complex mechanical environment.3D perfusion system provides a spatial bone marrow gradient and dense cell distribution,which better simulate the hematopoietic microenvironment,has been widely used in stem cell culture.Moreover,scaffold structure is closely related to cell activity,and the mechanical excitation generated by fluid flow during dynamic culture has an important impact on the biological functions of stem cells.Various studies have shown that the morphology and structure of the scaffold may play a role in inducing erythropoiesis as a key factor in simulating the mechanical environment of bone marrow.However,the current laboratory technology is difficult to accurately measure the mechanical environment parameters within the scaffold,and this problem can be solved by finite element method.In this study,the finite element models with different morphologies were established based on mechanical design combination with finite element method,the permeability of the scaffold and mechanical stimuli in scaffolds were analyzed quantitatively in different flow rates.The main contents and results are as follows:(1)Preparation and characterization of natural acellular cancellous bone scaffold.Micro-CT and other methods were used to characterize the cancellous bone scaffolds.The pore diameter distribution is 50-800μm,and the wall thickness is concentrated between 50-150μm.The effective parameters of cancellous bone structure were extracted,and three kinds of pore shapes were proposed as round,square and regular hexagonal,which provided a theoretical basis for ideal model design.(2)Build ideal models and analyzed the material transport characteristics of the scaffold.According to the obtained scaffold structural parameters and typical cell structures,three 3D scaffold structures with different pore morphology(round,square and hexagon)were established by using Solid Works 3D modeling software,and each scaffold had three different porosity(55%,70%,85%).The results showed that the change of porosity was more sensitive to the performance of the scaffold than the pore shape,and pore shape has little effect on the fluidity,permeability,velocity and pressure distribution of the scaffolds.Among all the scaffold models,the permeability of round porous scaffold with porosity of 85% was the closest to human cancellous bone,and square scaffold has better nutrient transport capacity.(3)Analyze the mechanical environment of the scaffolds with different structure at various flow rates.Simulation results of the mechanical environment of scaffolds showed that the distribution of mechanical excitation was controlled by porosity and scaffold morphology.In the low porosity scaffolds,Wall shear stress(WSS)in the hexagonal scaffolds was prone to extreme values,while the mechanical environment of square and round scaffolds is more suitable for cell culture.The distribution of WSS is generally uniform in high porosity scaffolds,especially in regular hexagonal scaffolds.WSS decreased with the increase of porosity.The flow rate was positively correlated with the average shear stress in the scaffolds.By controlling the flow rate,the mechanical excitation in the scaffold can be adjusted to achieve a hematopoietic mechanical microenvironment which conducive to stem cell culture.In this study,the performance of the scaffold was evaluated from multiple perspectives,which provides a theoretical basis for designing scaffold structure and applying flow rates when simulating the hematopoietic microenvironment of bone marrow in vitro.The nine scaffold models can be used as the basis on perfusion culture experiment and provides a more intuitive analysis for application and the mechanical environment of scaffolds in vitro culture... |
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