Research On Mechanical Stimulation Of Tissue Engineering Blood Vessel Cultured In Bioreactor Under Bilayer Model Structure

Cardiovascular disease has now become the disease with the highest mortality rate in the world,and vascular disease is the main cause of cardiovascular disease.Since vascular grafts and vascular bypass have always been the main means to replace diseased blood vessels,the clinical demand for vascular grafts(especially small-caliber(<6 mm)vascular grafts)has always been great.At present,self-vessels are used as the main source of vascular grafts,but due to the limited sources and the difficulty of quality assurance,it is necessary to find suitable artificial blood vessels to solve this clinical need.Tissue engineering technology is currently the most promising method for constructing vascular grafts,and some laboratories have prepared vascular grafts with certain mechanical properties,and these mechanical properties are mainly formed by giving cultured cells and tissues a certain mechanical stimulation.However,there are few researches on mechanical stimulus analysis and change rules in the process of tissue engineering blood vessel construction.In this paper,different research contents are designed to solve the problems of inaccurate and incomplete quantification caused by the complexity of mechanical stimulation in the process of tissue engineering blood vessel construction.It is mainly divided into the following three aspects:(1)Tissue engineered blood vessels were cultured in bioreactor for 8 weeks based on biodegradable polymer scaffolds,and compare the growth of tissue-engineered blood vessels in the dynamic and static groups;the results showed that the content of tissue engineered vascular smooth muscle cells and extracellular matrix components in the dynamic group was higher than that in the static group,the structure was more orderly,and the distribution was more uniform.Since the mechanical properties of blood vessels are mainly contributed by smooth muscle cells and extracellular matrix,appropriate mechanical stimulation can significantly improve the mechanical properties of tissue-engineered blood vessels.At the same time,the strain at the beginning and the end of the culture was compared,and the results showed that the strain of the tissue-engineered blood vessel at the end of the culture was significantly smaller than the initial strain,and the cultured strain of the tissue-engineered blood vessel changed continuously with the culture time during the process of tissue engineering blood vessel construction.At present,there is a significant error in using the strain of the silicone tube as the mechanical stimulation of the seed cells without considering the constraint effect of tissue engineering blood vessels on the silicone tube.(2)Use the silicone rubber material to simulate the restraint effect of tissue engineering blood vessels on the silicone tube,and compare and analyze the strain of the silicone tube and the outer layer material under different loading pressures in the tube with or without the outer layer material restraint.The results show that the strain of the silicone tube under the constraint of the outer material is significantly smaller than that without external constraints.At the same time,the experimental data can be used to verify the analytical and numerical solutions of the bilayer model.Find a method that can be used to simulate and study the restraint effect of tissueengineered blood vessels on silicone tubes,and to analyze the stress and strain of tissueengineered blood vessels.(3)Using the theory of elasticity to derive the analytical solution of the stress and displacement of the double-layer tubular structure under the pressure in the tube,and analyze the influence of the loading pressure in the tube,the elastic modulus of tissue engineering blood vessels,and the elastic modulus of silicone tube on the stress and strain.The results show that the increase of the loading pressure in the tube can simultaneously increase the stress and strain of the tissue engineering blood vessel;the increase of the elastic modulus of the tissue engineering blood vessel can reduce the strain of its culture,but the stress increases;the elastic modulus of the silicone tube increases can cause the stress and strain of tissue engineering blood vessels to decrease.Comparing the analytical solution with the experimentally measured results verifies the correctness of the analytical solution of the bilayer model,and provides a basis for the stress-strain analysis of tissue-engineered blood vessels and the optimization of mechanical stimulation conditions in the future.The finite element software ANSYS was used to analyze the stress and strain of tissue-engineered blood vessel with bilayer tubular structure under the condition of pressure in the tube.Using the same parameters as the analytical solution of the bilayer model,the calculated numerical solution was compared with the analytical solution of the bilayer model and the experimental results.The results show that the error of the numerical solution calculated by the finite element method can be controlled within a small range no matter compared with the experimental results or the analytical solution of the bilayer model.At the same time,finite element analysis is one of the most widely used numerical calculation methods in the engineering field.The finite element method has its obvious advantages;the emergence of finite element analysis software allows users not to spend a lot of time deriving complex formulas and mathematical models.Only given the parameters of the mechanical model corresponding to the research problem(parameters such as size geometric parameters,mechanical parameters,constraints and boundary conditions),the corresponding numerical approximate solution can be calculated.Under certain conditions,this approximate solution is very close to the analytical solution,and it is very convenient to use,which can save a lot of time and cost.The bilayer model used in this study can solve the problem of significant error compared with the actual value of the current single-layer structure to quantify the mechanical stimulation,and further quantify the mechanical stimulation of the seed cells during the construction of tissue engineering blood vessels.It can be used to guide the mechanical culture conditions of tissue engineering blood vessels,and continuously optimize the parameters suitable for tissue engineering blood vessel culture.