Fabrication And Mechanical Properties Of Polycaprolactone-based Small-diameter Artificial Vascular Based On Supercritical Foaming

The death rate of cardiovascular diseases in China has accounted for more than40%of the disease deaths.At present,the main method of clinical treatment in vascular surgery is to replace the diseased vessels with grafts by means of vascular bypass treatment.However,it is short of autologous vascular donors and it will cause damage to other parts of the body,and the allogeneic transplantation will cause inflammatory reaction.Small diameter artificial blood vessels can replace the damaged vessels with a certain mechanical strength and provide a carrier for the regeneration of cell and blood vessel.It is a hot topic that how to mimic the microstructure of human blood vessels and prepare small diameter artificial blood vessels with both biological and mechanical properties of natural blood vessels.In this paper,biodegradable polycaprolactone（PCL）blends with different mechanical properties were prepared based on PCL.By using supercritical Microcellular Foaming Technology（Sc CO₂）,the micro structure of small diameter artificial blood vessels was optimized through material components and preparation process,and the three dimensional porous small diameter artificial blood vessel with high cell connectivity,ideal mechanical properties that are suitable for cell adhesion and growth were prepared,It is expected that a new method for the preparation of biodegradable artificial blood vessels and be explored and a theoretical basis and data support for broadening the preparation technology of small diameter artificial blood vessels can be provided.First,it is important to conduct research on preparation of PCL tubular structure and research on microcellular foaming process.The internal interconnected porous structure is the necessary microstructure of ideal small-diameter artificial blood vessel.This chapter focuses on the microcellular foaming process window and cell structure control of PCL small-diameter tubular structure.Small diameter porous PCL tubular structure with inner diameter of 3 mm and outer diameter of 4 mm was successfully prepared based on the tubular mold designed by our laboratory and Sc CO₂ intermittent microcellular foaming process.Through the optimization of microcellular foaming process parameters,it was found that under the conditions of saturated CO₂,holding time 1H,temperature 50℃and saturation pressure 2000 psi,the internal porosity of PCL tubular structure was 79%,the longitudinal tensile strength was 1.25 MPa,the elongation at break was more than 200%,and the compliance index 7.52 was close to natural blood vessels.It basically meets the mechanical properties requirements of natural blood vessels.However,under the stress level of 1.68 MPa,the elastic recovery of tubular structure is poor after repeated loading and unloading process,and the bubble stability of PCL tubular structure is poor,and the opening rate is only 60%.In order to further improve the cell stability of PCL tubular structure,polylactic acid（PLA）was introduced into PCL matrix to make PCL/PLA blends.PLA can be used as heterogeneous nucleating agent to improve the microcellular foaming properties of PCL.PLA exists in the PCL matrix as dispersed phase,which not only improves the melt strength of PCL,but also improves the microcellular foaming performance of PCL as heterogeneous nucleating agent.With the increase of PLA content from 10%to 30%,the cell diameter in the artificial blood vessel decreased to10.78μm,the highest cell density was 8.9×10⁸cell/cm³,and the highest pore opening rate was 72%,which shows a significant effect of heterogeneous nucleation.In addition,the inner diameter of the artificial blood vessel showed an obvious"skin core"multi-layer microstructure,which means the surface of the artificial blood vessel is compact and smooth,and the inner cell diameter presented an increasing gradient trend.The mechanical properties test showed that the compliance of PCL/PLA small-diameter vascular with 10%PLA and 20%PLA was consistent with that of human femoral artery.The tensile strength of samples with 20%PLA was the highest,but its elastic recovery was smaller than that of pure PCL tubes after cyclic loading and unloading.The biocompatibility of human umbilical vein endothelial cells（HUVECs）showed that cells cultured on PCL/PLA small diameter artificial blood vessels with 20%PLA proliferated faster and spread in a larger area.The addition of PLA improved the microcellular foaming ability and cell connectivity of PCL,but the elasticity of artificial blood vessels still required to be improved compared with pure PCL.In this part,PCL/PLCL blends were made by introducing poly（L-lactide co caprolactone）（PLCL）into PCL matrix.Scanning electron microscope（SEM）characterization showed that PLCL existed in PCL matrix as fibrous morphology.The low-frequency end effect of storage modulus in structural rheological test further confirmed that PLCL fiber dispersed phases entangled with each other to form a three-dimensional network structure,which not only enhanced the melt strength of PCL matrix,but also maintained the high elastic recovery ability of pure PCL.When the PLCL content is less than 30%,the good compatibility between PCL and PLCL strengthens the homogeneous nucleation effect and weakens the heterogeneous nucleation effect at the interface,and the overall homogeneous nucleation ability of the composite system is improved.The results of microcellular foaming showed that with the increase of PLCL content,the cell diameter gradually increased to 26.27μm,and the maximum open cell rate was 72%.Regarding the mechanical properties,compared with the pure PCL tubes,the tensile strength and elongation at break of PCL/PLCL small diameter artificial blood vessel with 10%PLCL increased by about 3 times and 2.3 times,respectively,which achieved the effect of synergistic reinforcement and toughening.Cell viability test showed that HUVEC cells cultured on PCL/PLCL small diameter artificial blood vessel with 10%PLCL proliferated faster and the cell morphology was clearer than that of the other two components.In order to further mimic the nonlinear mechanical behavior of natural blood vessels.In this part,we select different PCL based small diameter artificial blood vessels to construct three-layer composite small caliber artificial blood vessels.According to the different elastic modulus of each layer of blood vessels,the load displacement piecewise function of three-layer composite small diameter blood vessels was constructed.Based on the ANSYS finite element analysis software,the numerical simulation of the load displacement tensile curve of the three-layer composite small diameter artificial blood vessel was carried out.The results showed that the three-layer composite small diameter artificial blood vessel presents a nonlinear mechanical behavior in line with the changes of blood flow pressure and blood vessel diameter in the natural blood vessel.The experimental results of tensile load displacement curve of three-layer composite small-diameter artificial blood vessel were consistent with the trend of stress displacement nonlinear variation of numerical simulation results.The tensile load displacement piecewise function of three-layer composite small-diameter artificial blood vessel can provide a mechanical theoretical support for the design and optimization of multi-layer composite artificial blood vessel.