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.

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.

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

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.

Multiple recurrent cystic echinococcosis with abdominal aortic involvement: A case report

BACKGROUND Recurrent cystic echinococcosis(CE)with vital organ involvement is a challenge for clinicians.Herein,we report a case of aortic involvement in recurrent retroperitoneal CE lesions following primary splenic CE resection.CASE SUMMARY A 60-year-old male was admitted due to progressive abdominal pain and poor appetite.He was diagnosed with multiple recurrent CE with abdominal aortic involvement according to preoperative evaluation.During surgical resection,major aortic bleeding accidentally occurred while dissecting the cyst,which was firmly attached to the abdominal aortic wall.Hemostasis attempts were conducted to deal with this emergency situation and maintain circulation.Postinterventional recovery was uneventful,and 2-year follow-up showed no sign of recurrence or any other complications.CONCLUSION Radical resection of recurrent complicated CE with aortic involvement should be carefully planned and performed to prevent possible severe adverse complications,thereby improving the postoperative outcome.

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.

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.

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.

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.

Thrombogenicity of biodegradable metals

Biodegradable metals offer a promising means to ameliorate many of the long-term risks associated with vascular devices made of conventional biostable stent metals.While numerous biodegradable metal alloys have been developed and characterized in animal models,knowledge of their blood reactivity and thrombogenicity remains unknown.Metal hemocompatibility is particularly valuable because current generation drug-eluting stents pose a significant long-term thrombosis risk.In this study,four pure metals,widely used as degradable base materials(Fe,Zn,Mg,and Mo),and three alloys commonly used in cardiovascular devices[NiTi,CoCr,and stainless steel(SS)]were evaluated.This work examined how each of these metals activate platelets,coagulation factors,and inflammation using in vitro hemocompatibility assays and a clinically relevant ex vivo non-human primate arteriovenous shunt model.Testing found that while all metals promoted a downstream activation of platelets and coagulation in flowing whole blood,platelet and fibrin attachment to Mg was markedly reduced.Additionally,Fe and Mo trended toward higher platelet attachment and contact pathway activation.Overall,the results suggest that Mg may delay clot initiation,but not eliminate clot formation,indicating the importance of understanding thrombosis in Mg alloys that are currently being developed for clinical use as biodegradable stents.

Zinc(Ⅱ)metal-organic framework eluting titanium implant as propulsive agent to boost the endothelium regeneration

The advent of antiproliferative drug-eluting vascular stents can dramatically reduce in-stent restenosis via inhibiting the hyperproliferation of vascular smooth muscle cells.However,the antiproliferative drugs also restrain the repair of the injured endothelial layer,which in turn leads to the very later in-stent restenosis.Evidence points that competent endothelium plays a critical role in guaranteeing the long-term patency via maintaining vascular homeostasis.Boosting the regeneration of endothelium on the implanted vascular stents could be rendered as a promising strategy to reduce stent implantation complications.In this regard,bioactive zinc(II)metal-organic framework modified with endothelial cell-targeting Arg-Glu-Asp-Val peptide was embedded in poly(lactide-co-caprolactone)to serve as a functional coating on the surface of titanium substrate,which can promote the proliferation and migration of endothelial cells.The in vitro cell experiments revealed that the zinc(II)metal-organic framework embedded in the polymer coating was able to modulate the behaviors of endothelial cells owing to the bioactive effects of zinc ion and peptide.Our results confirmed that zinc(II)metal-organic framework eluting coating represented a new possibility for promoting the repair of the damaged endothelium with potential clinical implications in vascular-related biomaterials and tissue engineering applications.

Inhibition of in-stent restenosis after graphene oxide double-layer drug coating with good biocompatibility

In this study,we designed a double layer-coated vascular stent of 316L stainless steel using an ultrasonic spray system to achieve both antiproliferation and antithrombosis.The coating included an inner layer of graphene oxide(GO)loaded with docetaxel(DTX)and an outer layer of carboxymethyl chitosan(CMC)loaded with heparin(Hep).The coated surface was uniform without aggregation and shedding phenomena before and after stent expanded.The coating treatment was able to inhibit the adhesion and activation of platelets and the proliferation and migration of smooth muscle cells,indicating the excellent biocompatibility and antiproliferation ability.The toxicity tests showed that the GO/DTX and CMC/Hep coating did not cause deformity and organ abnormalities in zebrafish under stereomicroscope.The stents with GO double-layer coating were safe and could effectively prevent thrombosis and in-stent restenosis after the implantation into rabbit carotid arteries for 4–12 weeks.