Fabrication And Characterization Of Fully Covered Biodegradable Biliary Stent And Compression Simulation Based On A Numerical Approach By Finite Element Method

Due to high morbidity,mortality and many complications,the disease from liver and gall has developed into the most threatening sickness for human,the most common one of which is benign and malignant biliary strictures,resulting in jaundice,cholangitis,pancreatitis,bile duct stones to seriously affect the quality of life.The preferred method to treat the biliary obstruction is interventional placement of biliary stent including endoscopic stenting or percutaneous transhepatic stenting,which obviously improve the bile drainage to relieve the pain relative with biliary stricture and cause less trauma from operation.The technical success rate for stenting biliary occlusion is greater than 90%,which has been approved from the doctor to heal the patients with biliary stricture.The biliary stent to date is frequently used in clinic involving the plastic stent and metallic stent,the long-term patency of which is not good because of high recurrent rate of adverse events including stent restenosis and migration so that the stent need be frequently changed resulting risk from therapy and financial burden.According to the adverse events above,It is very important to study fully covered biodegradable biliary stent(FCBBS),which can be used in stenting biliary stricture for duration of patency and be degraded into non-toxic element for human body after finishing stenting,the stent occlusion could be prevent by the film part of FCBBS to reduce risk of complication.In this work,firstly,the structure of FCBBS was designed through textile technology,secondly,the materials used for FCBBS was choose to fabricate a serial of FCBBS with different parameter,and the FCBBSs were conducted to compression test to investigate the effect of structure parameter of FCBBS on the compression behavior,finally,the finite element method(FEM)was applied to simulate the compression behavior of FCBBS for illustrating variation of stress and strain in the compression process and declaring difference of stress and strain of stent covered before and after.In view of the structure of biliary stent produced by developed country,a special FCBBS was designed,which was composed of non-covered biodegradable biliary stent(NCBBS)and coating membrane.According to braiding principle of stent,NCBBS with structure of rhombus was prepared by braid-hand method using a self-made cylinder of copper pipe mould invented by Donghua university first,which was characterized with high porosity,many interlacing points,integrity structure,and then FCBBS was fabricated by covering the membrane with features of high porosity,much thin fiber and high special surface area on NCBBS using electrospinning method.The biodegradable materials with great biocompatibility and safety,such as polydioxanone(PDO)and polycaprolactone(PCL),was considered as the materials for manufacturing FCBBS.On the first hand,the mechanical property and degradation of PDO in vitro was studied,The conclusion is below: the PDO monofilaments with 3 kinds of diameter were conducted to tensile and bending test,it is clearly found that the PDO presented the better mechanical performance and tensile strength of PDO monofilament increase with growing the value of PDO diameter consistent with bending strength.Based on the result of degradation of PDO monofilament in vitro,in the first 8 weeks of the whole degradation process,the surface morphology of PDO maintained very well,quality variation of PDO decreased very small,the retention rate of quality of PDO kept more than 97.5%,the cracks in the surface of PDO have been emerged in the 12-16 weeks followed,finally,there are some small pieces of material which was split away off PDO monofilament,the quality retention rate still hold bigger than 80.4% after 16 th weeks;The tensile and bending strength of PDO in the whole degradation process maintained about 12 weeks,tensile strength of PDO decreased gradually as degradation continued same with bending,at 10 th weeks,the retention rate of tensile strength just was 16.39%,and PDO turn into fragile monofilament which cannot be afforded to tensile;The effect of technological parameter of electrospinning method on the characteristics of the membrane including morphology and diameter of the fiber,porosity,surface to volume ratio and mechanical performance was investigated to obtain great electrospinning manufacturing parameter for membrane of FCBBS.The most suitable technical parameter for producing the electrospinning membrane of FCBBS was that the solute concentration of PCL was 18.0 g/100 ml,the volume fraction of Dimethyl Formamide(DMF)was 43%,the voltage of electrospinning facility is 15 kv.According to the braiding method of NCBBS,the NCBBSs with different structure parameter were fabricated firstly,NCBBS and MTN-DA Ni-Ti alloy biliary stent which has been successfully applied in treating patient were covered with PCL by optimized electrospinning method to obtain FCBBSs with different structure parameter and fully covered MTN-DA Ni-Ti alloy biliary stent(FCM),the two kinds of covered biliary stent above were conducted to compression test to analyze the variation of compression behaviors of them and the difference of FCBBSs which were covered before and after.The conclusion is below: 12 kinds of FCBBSs with different structure parameter and 1 kind of FCM were successful to manufacture,through their compression test,the compression-recovery curve of FCBBS and FCM was basically same that the plastic deformation has been emerged;The maximal compression force of FCBBSs with same diameter increased with growing the braid-pin number,and the maximal compression force of FCBBSs with same braid-pin number enlarged with raising the PDO diameter;Comparing the maximal compression force between FCBBSs and FCM,it is easily found that the maximal compression force of 12 braid-pins FCBBS with 0.29 diameter of PDO was bigger than that of FCM,however,10 brain-pins FCBBS with 0.23 diameter was close up to FCM.The maximal compression force of 3 kinds of braid-pin number(8pins,10 pins,12pins)of FCBBSs with 0.36 mm PDO diameter were greater than that of FCM,the result above could show that FCBBSs we design could reach the requirement of clinic;After covering NCBBSs,the maximal compression force of FCBBSs were bigger than relative NCBBSs.Based on the structure of specimens of FCBBSs and NCBBSs,the numerical models of FCBBSs and NCBBSs were respectively established by Solidworks software in the first step,the numerical compression models of FCBBSs and NCBBSs were constructed by ABAQUS software to analyze the relationship between structure parameter and the stress,strain of the stent or the effect of membrane on the stress,strain of stent.The conclusion is below: the linear-elastic behaviors of 0.36 mm monofilament NCBBS model with 4 kinds of braid-pin number(6pins,8pins,10 pins,12pins)were simulated firstly,furthermore,the experimental result of the compression test was compared with simulation above,from the comparison results,it is clear that the simulation and experimental results have good agreement with each other,indicating that the simulation results can be given a reference to the investigation of biliary stents;The compression force of NCBBSs increased with growing of the braid-pin number,the value of the compression force of 0.36 mm diameter NCBBS with 12 braid-pins was the highest,followed by 10 and 8 braid-pins,the worst stent was 6 braid-pins NCBBS;The stress concentration of NCBBS was distributed mainly in the archway zone of two stent head-ends and the positions of interlacing point.The maximal internal stress of NCBBSs enlarged with increasing of braid-pin number,and the more bigger stress NCBBSs had,the more easier damage in NCBBSs was happened,so damage was the most easy to be produced in NCBBS with 12 braid-pins.9 kinds of FCBBSs with different monofilament and brain-pin number were conducted to compression test and analyze the elastic-plastic behaviors in the compression simulation,there was good agreement between experimental and simulation.The compression force of FCBBS extracted from their numerical compression model increased with enlarging of monofilament diameter consistent with effect of braid-pin number;The stress concentration distributed heterogeneous was mainly occurred at the positions of head-end,sides and central of NCBBS part of FCBBS and was varied dramatically,however,the stress concentration distributed homogeneous was emerged in the positions of head-end and central of membrane part of FCBBS and varied gently;Comparing the maximal stress of FCBBSs with different structure parameter,when the monofilament diameter of FCBBSs was same,the maximal stress of FCBBSs increased with growing of braid-pin number same with the parameter of monofilament diameter;The plastic dissipation energy of the FCBBSs enlarged with growing of compression time,the maximal value of plastic dissipation energy of 0.29 mm monofilament diameter FCBBS with 12 braid-pins and 0.36 mm monofilament diameter FCBBS with 12 braid-pins was superior than the other 7 kinds of FCBBS indicating that 2 stents above were difficult to produce the plastic strain;The plastic strain obviously has been occurred in 9 kinds of FCBBS,but the plastic strain of 8,10,12 braid-pin number of FCBBSs with 0.23 mm diameter and 8,10 braid-pin number FCBBSs with 0.29 mm diameter have been only produced on the outside film part of FCBBSs in the compression process.Based on the plastic-elastic simulation result of numerical compression model of FCBBS and NCBBS,the compression force from numerical compression model of FCBBSs was bigger than that of corresponding NCBBSs;By comparing the maximal stress of FCBBSs and NCBBSs,it is clear that the maximal stress of FCBBSs was bigger than that of corresponding NCBBS;The plastic dissipation energy of FCBBSs and NCBBSs has same trend with the compression force above;The maximal plastic strain of 9 kinds of FCBBSs with different structure parameter was higher than zero indicating that the plastic deformation has been occurred in the FCBBS,however,the plastic strain has just been emerged in 0.36 mm PDO diameter NCBBSs with 3 types of braid-pins(8pins,10 pins,12pins);Through comparing the maximal plastic strain of NCBBS part of FCBBS and relative NCBBS,the plastic strain has been occurred in the NCBBS part of 0.36 mm monofilament diameter FCBBSs with 3 kinds of braid-pins(8pins,10 pins,12pins)and 0.29 mm monofilament diameter FCBBS with 12 braid-pins,but the plastic strain has just been emerged in 0.36 mm monofilament diameter NCBBS with 3 kinds of braid-pins(8pins,10 pins,12pins).To study the degradation regularity in vitro,FCBBS was put into tube filled sterility bile,and the live cell and FCBBS were cultivated together to investigate the biocompatibility.The following conclusions were established as below: before degradation,the structure of FCBBS was intact,the color of PDO monofilament of FCBBS was bright blue,and intact PCL membrane without a crack adhered tight to NCBBS part of FCBBS.The color of PDO faded gradually and changed slowly into translucent with degradation,the conglutination between PCL membrane and NCBBS part of FCBBS was weakened and PCL membrane began to split away off the NCBBS part of FCBBS,and in the later stage of degradation process,the crack was generated on the surface of PDO monofilament,furthermore,the PDO monofilament of FCBBSs was fractured completely so that FCBPBSs were collapse indicating radial supporting force was lost;All 9 kinds of FCBBSs exhibit the same tendency in the degradation process,in the first 2 weeks,the maximal compression force of FCBBS dramatically decreased,and unstably increased in 2-10 weeks followed,however,the maximal compression force of FCBBS was significantly fall down until could not be tested because of their collapse in the middle and later periods of degradation.The compression force of 0.36 mm monofilament diameter FCBBSs with 3 kinds of braid-pin number(8pins,10 pins,12pins)kept the most longest time in the degradation process about 22 weeks,the middle were 8,10,12 braid-pins number FCBBSs with 0.39 mm monofilament diameter about 20 weeks,and the shortest time were 0.23 mm monofilament diameter FCBBSs with 3 kinds of braid-pin number(8pins,10 pins,12pins)about 16 weeks indicating that degradable time of FCBBSs increased with growing of the PDO diameter of FCBBSs;The quality loss of FCBBSs was very little in first 8 weeks of whole degradation process,however,quality loss of FCBBSs began to quickly fall down after eighth week,and dramatically declined in the last four weeks in the whole degradation process;By culturing the HUVECs with PCL film and PDO monofilament together,HUVECs were very easy to attach on the surface of PCL film and PDO monofilament,spread and proliferate after 7 days culture demonstrating that FCBBS exhibit good biocompatibility.In conclusion,the systematic investigation had been conducted in structure design,choosing suitable materials,fabrication,performance test and simulation by FEM for FCBBS and could be as a reference to optimize the stent structure and clinic application.