Shape Optimization And Experimental Validation Of Biodegradable Magnesium-based Alloys Vascular Stent

The biodegradable magnesium-based alloys stents(BMg S)contain Mg-based alloys stents and bioabsorbable drug-eluting polymer coatings.BMg S support the vascular lesion for three to five months and biodegrade into pieces after the vasomotion return to normal.In this way,the rigid constraint of bare-metal stent(BMS)or drug-eluting stent(DES)on vascular vessel could be avoided,as well as permanent foreign body reaction.The development of BMg S provides a new choice for coronary artery disease(CAD)patients.However,the performance of BMg S requires special attention to non-uniform residual stress distribution and stress concentration,which can accelerate localized degradation after implantation.In the present dissertation,the author reported a novel concept in stent shape optimization with crimping-introducing,via finite element method(FEM)toolkit.A MgNd-Zn-Zr alloy with uniform degradation behavior served as the basis of our BMg S.Comprehensive in vitro evaluations drove stent optimization,based on observed crimping and balloon inflation performance,measurement of radial strength,and stress condition validation via microarea-XRD.The mechanical properties of BMg S were enhanced by design optimization compared to sine-wave stent,resulting in the decrease of dog-boning effect(28.3% vs.22.1%),longitudinal foreshortening(2.7% vs.0.6%)and the increase of the radial strength(88.8 k Pa vs.96.7 k Pa).With the raised platform and shape optimization,the percentage of high-stress regions of stent(4.12% vs.0.68%)and vascular vessel(22.75%to 5.25%)was decreased significantly.BMg S exhibit deficient corrosion period for clinic applications,making the protective polymer coating more crucial than DES with the permanent metal scaffold.We implemented a cohesive method based on finite element analysis method to predict the integrity of adhesive between coating and stent during the crimping and deployment.For the first time,three-dimensional quantitative modeling reveals the process of polymer coating delamination and stress concentration.The fracture and micro-cracks of coatings were consistent with the simulation result,confirmed by the scanning electron microscopy observation.Moreover,we analyzed four possible factors,i.e.,stent material,stent design,coating polymer and thickness of the coating,which would affect the stent-coating damage and the distribution of the stress in coatings.Mg-Nd-Zn-Zr alloy with lower yield strength performed a more uniform strain distribution and more favorable adhesion of the coating than the commercial magnesium alloy AZ31.Shape optimization of stent design improved the strain and stress distribution of coating remarkably and avoided coating delamination.Additionally,PLGA coating with lower elastic modulus and yield strength tends to follow the deformation of the stent better and to adhere on the surface more tightly,compared to PLLA polymer.A reduction in coating thickness and an increase in the strength of stentcoating interface improve the resistance to delamination.Our framework based on cohesive method provides an in-depth understanding of stent-coating damage and shows the way of computational analyses could be implemented in the design of coated biodegradable magnesium stents.Moreover,a Rapamycin-eluting polymer coating was sprayed on the shape optimized BMg S to improve the corrosion resistance and release anti-hyperplasia drugs.In vivo evaluation of the optimized coated BMg S was conducted in the iliac artery of New Zealand white rabbit with quantitative coronary angiography(QCA),optical coherence tomography(OCT)and micro-CT observation at 1,3,5-month follow-ups.Neither thrombus or early restenosis was observed,and the coated BMg S supported the vessel effectively prior to degradation and allowed for arterial healing thereafter.Rapamycin-eluting coating optimized stents exhibit suitable biocompatibility and unfailing support ability to vessel no less than three months,besides the vasomotion was restored at five months post implantation.The proposed shape optimization framework based on FEM provides a novel concept in stent design and in-depth understanding of how deformation history affects the biomechanical performance of BMgS.