Research on the Microstructure Construction Technology of Fully Degraded Polymer Vascular Stent Based on Electric Field Driven 3D Printing

The so-called fourth-generation biodegradable vascular stent has become a research hotspot in thefield of bioengineering because of its good degradation ability and drug-loading characteristics.However,the preparationof polymer-degraded vascular stents is affected by known problem such as poor processflexibility,low formingaccuracy,large diameter wall thickness,limited complex pore structure,weak mechanical properties of radial support and high process cost.In this study,a deposition technique based on a high-voltage electric-field-driven continuous rotating jet is proposed to fabricate fully degraded polymer vascular stents.The experimental results showthat,due to the rotation of the deposition axis,the deposition direction of PCL(polycaprolactone)micro-jet isalways tangent to the surface of the deposition axis.The direction of the viscous drag force is also consistent withthe deposition direction of the jet.It is shown that by setting different rotation speeds of deposition axisωandlinear motion speeds of the nozzle V,the direction of rotation,pitch and angle of the individual printed spiralcurve can be precisely tuned.In the process of multiple spiral curves matching the deposition forming thin walltube mesh,the mesh shape and size of the thin wall tube can be accurately controlled by changing the number ofmatching spiral curves and the size of the matching position bias distance.Finally,the characteristics of a PCLtubular stent sample(with uniform-size microfibers and mesh shape),fabricated under the appropriate processparameters are described in detail.

Composite bioabsorbable vascular stents via 3D bio-printing and electrospinning for treating stenotic vessels

A new type of vascular stent is designed for treating stenotic vessels. Aiming at overcoming the shortcomings of existing equipment and technology for preparing a bioabsorbable vascular stent （BVS）, a new method which combines 3D bio-printing and electrospinning to prepare the composite bioabsorbable vascular stent （CBVS） is proposed. The inner layer of the CBVS can be obtained through 3D bio- printing using poly-p-dioxanone （PPDO）. The thin nanofiber film that serves as the outer layer can be built through electrospinning using mixtures of chitosan-PVA （poly （vinyl alcohol））. Tests of mechanical properties show that the stent prepared through 3D bio-printing combined with electrospinning is better than that prepared through 3D bio- printing alone. Cells cultivated on the CBVS adhere and proliferate better due to the natural, biological chitosan in the outer layer. The proposed complex process and method can provide a good basis for preparing a controllable drug-carrying vascular stent. Overall, the CBVS can be a good candidate for treating stenotic vessels.

Biocompatibility of vascular stents manufactured using metal injection molding in animal experiments

This study aimed to evaluate the feasibility and safety of a novel stent manufactured by metal injection molding(MIM)in clinical practice through animal experiments.Vessel stents were prepared using powder injection molding technology to considerably improve material utilization.The influence of MIM carbon impurity variation on the mechanical properties and corrosion resistance of 316L stainless steel was studied.In vitro cytotoxicity and animal transplantation tests were also carried out to evaluate the safety of MIM stents.The results showed that the performance of 316L stainless steel was very sensitive to the carbon content.Carbon fluctuations should be precisely controlled during MIM.All MIM stents were successfully implanted into the aortas of the dogs,and the MIM 316L stents had no significant cytotoxicity.The novel intravascular stent manufactured using MIM can maintain a stable form and structure with fast endothelialization of the luminal surface of the stent and ensure long-term patency in an animal model.The novel intravascular stent manufactured using MIM demonstrates favorable structural,physical,and chemical stability,as well as biocompatibility,offering promising application in clinical practice.

Vascular morphological change due to endovascular stent placement for intracranial aneurysm

Objective The purpose of this study was to quantify the vascular angle change due to intracranial stent placement and its effect on hemodynamics. Methods Fifteen patients with a wide-necked anterior communicating artery aneurysm were treated with stent-assisted coiling. Centerlines of the parent vessels were calculated and determined the exact change in

Study on ultrasonic spray technology for the coating of vascular stent

The ultrasonic spray technology is studied by the method of theoretical derivation, CFD simulation, spray particle diameter detection and analysis, and experimental analysis. And the ultrasonic spray process for the coating of vascular stent is also optimized. Firstly, the ultrasonic atomization physical model is established and the equation of atomization particle diameter is derived. Secondly, the ultrasonic atomization process is simulated by the CFD method, and shows three atomization patterns： incomplete atomization pattern, critical atomization pattern and jet atomization pattem. The critical amplitude and power equation for ultrasonic atomization is derived. Thirdly, experiment is conducted to study the influence of parameters including power, gas pressure, and surface tension. The results show that the spray is stable though few particles are likely to collide each other during spray moving, and the droplet diameter is about 10μm. The Rosin-Rammler distribution equation for ultrasonic spray is created, and the uniform index number is between 7.11 and 11.48. The uniformity of spray particle diameter, the efficiency of adjustment and the energy consumption are better than traditional spray technology. Lastly, the ultrasonic spray process parameters for stent coating are optimized to eliminate the common defects and obtain fine coating.

Structural and mechanical aspects of hypoeutectic Zn–Mg binary alloys for biodegradable vascular stent applications

The study is concerned with the mechanical properties of Zn and three Zn–Mg double alloys with Mg concentrations:0.5%,1.0%and 1.5%in the form of rods with a diameter of 5 mm as potential materials for use in biodegradable medical implants,such as vascular stents.The materials were cast,next conventionally hot extruded at 250°C and finally,hydrostatically extruded(HE)at ambient temperature.Occasionally HE process was carried at liquid nitrogen temperature or in combination with the ECAP process.After HE,the microstructure of the alloys was made up of fine-grainedαZn of mean grain size~1μm in a 2-phase coat of 50–200 nm nanograins of the fineαZn+Mg2Zn11 eutectic.The 3 to 4-fold reduction of grain size as a result of HE allowed an increase in yield strength from 100%to over 200%,elongation to fracture from 100%to thirty fold and hardness over 50%compared to the best literature results for similar alloys.Exceptions accounted for elongation to fracture in case of Zn-0.5 Mg alloy and hardness in case of Zn-1.5 Mg alloy,both of which fell by 20%.For the Zn-0.5 Mg and Zn–1Mg alloys,after immersion tests,no corrosive degradation of plasticity was observed.Achieving these properties was the result of generating large plastic deformations at ambient temperature due to the application of high pressure forming with the cumulative HE method.The results showed that Zn–Mg binary alloys after HE have mechanical and corrosive characteristics,qualifying them for applications in biodegradable implants,including vascular stents.

Vascular stent as a treatment for refractory cervical stenosis

Cervical stenosis is a clinical condition involving partial or complete obstruction of the endocervical canal.In 1996,Bauldauf proposed that the definition of cervical stenosis is a cervical canal into which a 2.5# Hegar dilator cannot be inserted.1 Acquired cervical stenosis can be a complication of surgical procedures such as conization,trachelectomy,and curettage.It is a serious complication because of the clinical repercussions,which can include amenorrhea,hematometra,dysmenorrhea,infertility,infection,and endometriosis.Various surgical techniques are used in dilation and cervix reconstruction.However,in some cases,unsuccessful dilation with refractory recurrent stenosis may lead to hysterectomy.A successful case in which a self-expanding nitinol vascular stent was used to treat cervical stenosis was described by Grund et al.2 Here we report two additional cases in which vascular stents were used to treat patients with recurrent cervical stenosis after cervical surgeries.

3D Printing of Biodegradable Polymer Vascular Stents:A Review

Biodegradable polymer vascular stents(BPVSs)have been widely used in percutaneous coronary interventions for the treatment of coronary artery diseases.The development of BPVSs is an integrated process that combines material design/selection,manufacturing,and performance characterization.Three-dimensional(3D)printing technology is a powerful tool for polymer stent fabrication.Current review studies have focused primarily on the material and structural design of polymer stents but have failed to comprehensively discuss different 3D printing approaches and stent characterization techniques.In this paper,we address these shortcomings by discussing 3D printing methods and their application in BPVSs.First,some commonly used 3D printing methods(including material extrusion,vat polymerization,and powder bed fusion)and potential 3D printing strategies(including material jetting and binder jetting)for fabricating BPVSs are discussed;furthermore,the main post-treatments are summarized.Then,techniques to characterize the morphology,mechanical properties,and biological prop-erties of the printed BPVSs are introduced.Subsequently,representative commercial BPVSs and lab-grade BPVSs are compared.Finally,based on the limitations of stent printing and characterization processes,future perspec-tives are proposed,which may help develop new techniques to fabricate more customized stents and accurately evaluate their performance.

Extracellular matrix and nitric oxide based functional coatings for vascular stents

Cardiovascular diseases cause huge morbidity and mortality worldwide.Recently,vascular stents have been most frequently used to treat cardiovascular diseases thanks to their effectiveness at dilating blood vessels and main-taining the circulation of blood.However,stent expansion leads to endothelium injury posing thrombogenic and in-stent restenosis(ISR).In addition,the bioinertness and an acute lack of endothelium-like function on the surface of implanted vascular stents compromise their performance.Functional coatings of vascular stents to mimic endothelium-and extracellular matrix(ECM)-like functions could prevent thrombosis,inhibit the over-growth of smooth muscle cells(SMCs),and promote the rapid restoration of native endothelium,hence effec-tively suppressing stent-related complications.Noticeably,ECM-based coatings including a multitude of bioactive molecular,such as growth factors,heparin,hyaluronic acid(HA)and so on,have been proven to play important effects on regulating ECs/SMCs behavior and improving blood compatibility of stents.Additionally,nitric oxide(NO),which is fundamental to the endothelium-mediated anti-thrombogenesity,anti-intimal hyperplasia and anti-inflammation,has been leveraged to improve vascular stent functions.Therefore,this review will highlight different strategies and biological role of ECM and NO based functional coatings on vascular stent.Lastly,some potential important factors for stents development are suggested as well.

Research and development strategy for biodegradable magnesium-based vascular stents:a review

Magnesium alloys are an ideal material for biodegradable vascular stents,which can be completely absorbed in the human body,and have good biosafety and mechanical properties.However,the rapid corrosion rate and excessive localized corrosion,as well as challenges in the preparation and processing of microtubes for stents,are restricting the clinical application of magnesium-based vascular stents.In the present work we will give an overview of the recent progresses on biodegradable magnesium based vascular stents including magnesium alloy design,high-precision microtubes processing,stent shape optimisation and functional coating preparation.In particular,the Triune Principle in biodegradable magnesium alloy design is proposed based on our research experience,which requires three key aspects to be considered when designing new biodegradable magnesium alloys for vascular stents application,i.e.biocompatibility and biosafety,mechanical properties,and biodegradation.This review hopes to inspire the future studies on the design and development of biodegradable magnesium alloy-based vascular stents.

4D printing of personalized shape memory polymer vascular stents with negative Poisson’s ratio structure:A preliminary study

Four-dimensional(4D)printing,integrates transformation information into three-dimensional(3D)-printed structures,which means that 3D-printed structures are able to change their shapes,properties,or functionalities over time.Here,two types of shape memory personalized vascular stents with negative Poisson’s ratio structure are developed via 4D printing.The genetic algorithm is used to optimize the structure.Axial compression tests,radial compression tests and three-point bending tests are carried out to study the mechanical properties of the stents.In addition,fluid-structure interaction and stress distribution during the shape recovery process are investigated based on finite element method.The shape memory behaviors of the stents are excellent and in vitro feasibility tests demonstrate that the stents can expand the simulated narrow blood vessel rapidly.Therefore,4D printed shape memory stents with negative Poisson’s ratio structure are highly promising for the treatment of vascular stenosis.

Rapid prediction method for nonlinear expansion process of medical vascular stent

A neural network model with high nonlinear recognition capability was constructed to describe the relationship between the deformation impact factors and the deformation results of vascular stent.Then,using the weighted correction method with the attached momentum term,the network training algorithm was optimized by introducing learning factor η and momentum factor ψ,so the speed of the network training and the system robustness were enhanced.The network was trained by some practi-cal cases,and the statistical hypothesis validation was made for the predictive errors.It was shown that the average difference between the intelligent predictive result of vascular stent deformation neu-ral network and the nonlinear finite element analysis result was less than 0.03%,and the trained net-work could perfectly predict the vascular stent deformation.Further more,the rapid evaluation tool for the vascular stent mechanics performance was established using the Pro/Toolkit and the intelligent neural network predictive model of vascular stent expansion.The proposed tool system with strong practicality and high efficiency can significantly shorten the product development cycle of vascular stent.

Effect of ^(125)I seeds and ^(103)Pd stents on proliferation of vascular smooth muscle cells

This study aims at the theoretical and practical evidence for prevention of restenosis in vitro.Vascular smooth muscle cell(VSMC)model was established using adherent cell culture methods.The proliferation of VSMC was investigated by the cell counting method and 3H-TDR implementation test.The results are as follows.(1) For ^125I-seeds,the inhibition rate was 29.3% at 74B1(P<0.05),35.2% at 148Bq(P<0.05)and 42.4% at 370Bq(P<0.05),For ^103Pd-implanted stents,the inhibition rate was 14.7% at 4.44MBq(P<0.05),24.0% at 5.92MBq(P<0.05) and 38.0%at 7.4MBq(p<0.05),There was no significant difference between the blank tests and non-radioactive tests.(2) 48 hours exposure from ^125I-seeds at 148Bq or ^103Pd-implanted stents at 7.4MBq did not result in VSMC's morphological alteration,but that from ^125I-seeds at 370Bq caused morphological changes,Both ^125I-seeds and ^103Pd0-implanted stents inhibit the VSMC DNA synthesis in vitro.The inhibition effects are significantly related to their exposure duration and doses.

Influence of Stent Implantation on the Expression of PCNA and Apoptosis in Injured Vascular Smooth Muscle Cells

Objectives To evaluate the impact of stent implantation on proliferation and apop-tosis in injured media vascular smooth muscle cells (VSMC) and to explore the mechanism of restenosis after stent implantation. Methods Fifty male New Zealand rabbits were randomized into two groups, including balloon group and stent group. Control group was set up. The samples were harvested on 3, 7, 14, 28, 56 days after operation and the following investigation was carried out: (1) Assessing the expression of proliferating cell nuclear antigen (PCNA) of media VSMC by the method of immunohistochemistry; (2) Analyzing apoptosis of media VSMC by DNA agarose gel electrophoresis and TUNEL technique. Results The expression of PCNA and apoptosis in stent and balloon groups were markedly increased compared with control groups. (1) Stent group induced significant increased expression of PCNA in the media VSMC compared with balloon group on 3 to 28 days. On day 7, the positive rates of PCNA were 24. 36±0. 55 % vs 18. 74±1. 09 % ( P < 0. 01 ); (2) From 3 to 28 days, stent group appeared obvious DNA ladder, while balloon group only had little trace ; (3) TUNEL method showed that stent group induced much more significant apoptosis than that of balloon group on 3 to 28 days. The highest rate of apoptosis appeared on day 7: 12. 42 ±1.13% vs 5. 54±0.53% (P<0. 01); (4) By calculating the ratio of the positive rate of PCNA to apoptosis, it showed that on 3 to 28 days, the ratio of balloon group was higher than that of stent group. There was obvious difference between two groups. Conclusions Stent group induces augmented proliferation and much more significant apoptosis of media VSMC than that of balloon group. It makes the ratio of proliferation to apotosis reduced and the severity of restenosis relieved after stent implantation.

Chronic mesenteric ischemia: Time to remember open revascularization

Chronic mesenteric ischemia is caused by stenosis or occlusion of one or more visceral arteries. It represents a therapeutic challenge and diagnosis and treatment require close interdisciplinary cooperation between gastroenterologist, vascular surgeon and radiologist. Although endovascular treatment modalities have been developed, the number of restenoses ultimately resulting in treatment failure is high. In patients fit for open surgery, the visceral arteries should be revascularized conventionally. These patients will then experience long term relief from the symptoms, a better quality of life and a better overall survival.

Brachial access technique for aortoiliac stenting revisited

We report a modified technique to perform iliac artery stenting through the brachial artery access. A 6F Brite tip sheath (Cordis, Jonhson & Jonhson Medical, Miami Lakes, FL, USA) is inserted into either brachial artery and a standard 4F Judkins Right diagnostic catheter was inserted over a 260 cm 0.038” Terumo Stiff wire (Terumo Corp, Tokyo, Japan) through the sheath. The catheter is navigated down to the aortic bifurcation, and after selecting the common iliac artery ostium, the wire is navigated through the lesion and advanced to the ipsilateral superficial femoral arteries. The catheter should be then moved forward over the wires beyond the lesion and the Terumo guidewire is replaced by two 0.038” 260 cm Supracor wires (Boston Scientific Corporation, San Jose, CA, USA). In order to facilitate advancement of the stent without risk of dislodgement as well as to check the position with low contrast dose injection, a 6 F (or 7F if large stent is selected) 90cm Shuttle Flexor introducer long sheath (Cook Group, Bloomington, IN, USA) should be advanced over the Supracor wire until it reaches the common iliac artery ostium. A road-map technique can be used to check the ostium position in order to properly deploy the selected stent. This technique promises to be safe and effective offering more support than guiding catheter technique; moreover it reduces the stress on the arterial vessel at the subclavian site and enables a stiff balloon or stent catheter to be advanced even through a very elongated and calcified aorta without the risk of stent dislodgement.

Different Responses of Cell Cycle between Rat Vascular Smooth Muscle Cells and Vascular Endothelial Cells to Paclitaxel

Summary： Although previous reports showed dmg-eluting stent （DES） could effectively inhibit neointima formation, in-stent restenosis （ISR） remains an important obstacle. The purpose of this study was to investigate different effects of paclitaxel on proliferation and cell cycle regulators between vascular smooth muscle cells （VSMCs） and vascular endothelial cells （VECs） of rats in vitro. The cultured VSMCs and VECs of rats from the same tissues were examined by using immunohistochemistry, flow cytometry and Western blotting in control and paclitaxel-treated groups. The results showed paclitaxel could effectively inhibit proliferation of VSMCs and VECs. However, as compared with VECs, prolif- eration of VSMCs in paclitaxel-treated group decreased less rapidly. The percentage of cells in G0-G1 and G2-M phases was reduced, and that in S phase increased after treatment for 72 h. The expression of cyclin D1 and B1, p27 and PCNA in VSMCs of paclitaxel-treated group was up-regulated, but that of p21 down-regulated as compared with VECs. It is concluded that there are significant differences in the expression of cell cycle regulators and proliferation rate between paclitaxel-treated VSMCs and paclitaxel-treated VECs, suggesting that the G1 S checkpoint regulated by paclitaxel may play a critical role in the development of complications of DES, which provides new strategies for treatments of ISR.

基于响应面法的血管支架拉伸、扭转性能优化及考虑加工精度影响的强度可靠性分析

为分析设计变量对血管支架拉伸性能、扭转性能的精准影响,进行血管支架拉伸性能、扭转性能优化,考虑加工精度的影响,进行血管支架的强度可靠性分析。方法:取血管支架支撑筋宽度、支撑筋长度、连接筋宽度和支架厚度为设计变量,应用斯皮尔曼等级相关系数法分析设计变量对血管支架拉伸刚度、扭转刚度等响应变量的精准影响;采用响应面方法进行以拉伸刚度、扭转刚度为目标进行血管支架的优化设计;对优化后的血管支架,考虑加工精度所致设计变量的随机性,利用六西格玛工具分析应力的概率分布。结果:对于血管支架拉伸刚度,支撑筋宽度和连接筋宽度灵敏度系数大,且均为正值;对于血管支架扭转刚度,支撑筋宽度灵敏度系数较大,且为负值;优化后的血管支架相比原始血管支架,拉伸刚度降低了11.5%;扭转刚度减小了50.6%;考虑加工精度所致设计变量的随机性进行可靠性分析,在可靠度为99.8%时,虽然血管支架的拉伸刚度和扭转刚度最大值高于优化值,但血管支架的最大应力满足强度条件。结论:支撑筋宽度对血管支架的拉伸性能影响最大,连接筋宽度次之,支撑筋长度和支架厚度影响较小;支撑筋宽度对血管支架的扭转性能影响最大,连接筋宽度、支撑筋长度和支架厚度影响较小;随机因素加工精度对血管支架优化目标有一定的影响,但优化结果仍是可靠的。本文提供了一种血管支架优化的思路:首先是进行基于目标的优化,然后考虑随机因素的影响进行基于概率的强度可靠性分析。

Endovascular interventions of the femoro-popliteal disease in the elderly

In the last few years the treatment of superficial femoral artery (SFA) occlusive disease has undergone greater changes in management including more aggressive endoluminal therapy, especially in the elderly patients who are at high risk for extra-vascular comorbidities from the surgical approach. While acute and chronic arterial limb ischemia is the conditions which the interventional cardiologists frequently encounter, the elderly population represents special problematic clinical and anatomical setting due to heavy calcification and poor distal run-off. Arterial thrombolysis, rheolytic thrombectomy, mechanical thrombectomy, laser angioplasty, cryoplasty, and new flexible long stents are some of the promising techniques to improve the technical and clinical outcomes in these elderly patients.