An Auxetic structure configured as oesophageal stent with potential to be used for palliative treatment of oesophageal cancer; development and in vitro mechanical analysis

Oesophageal cancer is the ninth leading cause of malignant cancer death and its prognosis remains poor. Dysphagia which is an inability to swallow is a presenting symptom of oesophageal cancer and is indicative of incurability. The goal of this study was to design and manufacture an Auxetic structure film and to configure this film as an Auxetic stent for the palliative treatment of oesophageal cancer, and for the prevention of dysphagia. Polypropylene was used as a material for its flexibility and non-toxicity. The Auxetic (rotating-square geometry) structure was made by laser cutting the polypropylene film. This flat structure was welded together to form a tubular form (stent), by an adjustable temperature control soldering iron station: following this, an annealing process was also carried out to ease any material stresses. Poisson’s ratio was estimated and elastic and plastic deformation of the Auxetic structure was evaluated. The elastic and plastic deformation behaviours of the Auxetic polypropylene film were evaluated by applying repetitive uniaxial tensile loads. Observation of the structure showed that it was initially elastically deformed, thereafter plastic deformation occurred. This research discusses a novel way of fabricating an Auxetic structure (rotating-squares connected together through hinges) on Polypropylene films, by estimating the Poisson’s ratio and evaluating the plastic deformation relevant to the expansion behaviour of an Auxetic stent within the oesophageal lumen.     

A computational study of crimping and expansion of bioresorbable polymeric stents

This paper studied the mechanical performance of four bioresorbable PLLA stents, i.e., Absorb, Elixir, Igaki–Tamai and RevaMedical, during crimping and expansion using the finite element method. Abaqus CAE was used to create the geometrical models for the four stents. A tri-folded balloon was created using NX software. For the stents, elastic–plastic behaviour was used, with hardening implemented by considering the increase of yield stress with the plastic strain. The tri-folded balloon was treated as linear elastic. To simulate the crimping of stents, a set of 12 rigid plates were generated around the stents with a radially enforced displacement. During crimping, the stents were compressed from a diameter of 3 mm to 1.2 mm, with the maximum stress developed at both inner and outer sides of the U-bends. During expansion, the stent inner diameter increased to 3 mm at the peak pressure and then recoiled to different final diameters after balloon deflation due to different stent designs. The maximum stress was found again at the U-bends of stents. Diameter change, recoiling effect and radial strength/stiffness were also compared for the four stents to assess the effect of design variation on stent performance. The effect of loading rate on stent deformation was also simulated by considering the time-dependent plastic behaviour of polymeric material.     

Measurement and Numerical Simulation of the Dilatation Behaviour of Coronary Stents

Experiments are carried out to examine the dilatation properties of metallic stents. Therefore a test rig has been developed. Also the dilatation behaviour of stents out of different materials are investigated. Additionally numerical simulations of dilatation are carried out. Because balloon expandable stent systems exist of the stent and a balloon catheter, the balloon catheter is examined before the investigation of the stent systems. The results show a reproducible and similar dilatation behaviour for all stents. Titanium as a material with an advanced biocompatibility shows advantages in the dilatation behaviour against the stainless steel stents. A qualitative equality between simulation and measurement of the dilatation behaviour can be noticed. The results indicate the possibility to numerically simulate and to optimise the dilatation behaviour by a combination of simulation and measurement. The preclinical measurement can be reduced to some prototypes.     

Numerical investigation of influence of number of stent cells and type of link on expansion and haemodynamic behaviour of balloon-expandable coronary stent

Coronary stents are tubular, mesh-like structures used to force open clogged artery. Mounted on an inflatable balloon, stent compresses calcified plaque inside atherosclerotic artery with an inflating device, which transfers the load through the compliant balloon, thus maintaining the patency of lumen. One of the contributors for success of angioplasty is type of stents, which mainly differs in its geometrical design. A clinician recommends a stent based on comparative advantages. An ideal stent should be flexible to manoeuver through tortuous artery, easy to expand, provide good scaffolding to the vessel, have less radial recoil and foreshortening, possess uniformity in expansion and induce minimum alteration in physiological blood flow dynamics. In a stent these parameters are in competition with each other and are optimized by trade-offs. The present work tries to sequentially investigate the effect of number of stent cells and type of links on the expansion and haemodynamics behaviour through computational analysis based on finite element and finite volume techniques. The study compares performance within same classes of designs rather than comparing the designs that are completely different form each other. Results show that more number of stent cells in longitudinal direction considerably decrease the radial recoil, but increase the foreshortening effect. Restenosis-prone zones are localized around the stent struts and are predominant during end of systolic phase of cardiac cycle. Shorter links are preferred for better recoil and favourable distribution of wall shear stress while longer links are preferred for favourable foreshortening.     

冠脉血管支架介入耦合系统力学行为数值模拟研究

针对冠脉支架植入术后引起的血管内再狭窄问题,开展了冠脉支架介入耦合系统力学行为的数值模拟研究。基于Ogden非线性弹性理论,构建了冠脉血管和动脉粥样硬化斑块的超弹性本构模型。通过非线性有限元法,建立了冠脉支架与狭窄血管的耦合作用模型,研究了冠脉支架在经历压握收缩、压握卸载、球囊扩张与球囊收缩等介入过程后的体内扩张性能,分析了冠脉支架的介入对狭窄血管损伤及再狭窄的力学影响因素。对比分析了S型支架和N型支架介入后狭窄冠脉血管的生物力学响应,数值计算结果表明：狭窄冠脉血管在支架支撑体波峰处存在较高的应力梯度,而且由于2种支架联接筋结构的类似性,血管内膜与斑块的应力分布规律一致。但是,N型支架的径向回弹率与轴向短缩率均小于S型支架,导致了更高的狭窄血管壁面峰值应力和应力梯度,更易于引起冠脉血管损伤造成血管内再狭窄。综上,该文提出的冠脉支架介入耦合系统力学模型,对于优化支架结构、抑制冠脉血管再狭窄问题,提供了重要的理论依据和临床参考。     

Stiffness and energy dissipation in polyurethane auxetic foams

Auxetic open cell polyurethane (PU) foams have been manufactured and mechanically characterised under cyclic tensile loading. The classical manufacturing process for auxetic PU foams involves multiaxial compression of the conventional parent foam, and heating of the compressed specimens above the T_m of the foam polymer. Eighty cylindrical specimens were fabricated using manufacturing routes modified from those in the open literature, with different temperatures (135 °C, 150 °C), compression ratios and different cooling methods (water or room temperature exposure). Compressive tensile cyclic loading has been applied to measure tangent modulus, Poisson’s ratios and energy dissipated per unit volume. The results are used to obtain relations between manufacturing parameters, mechanical and hysteresis properties of the foams. Compression, both radial and axial, was found to be the most significant manufacturing parameter for the auxetic foams in this work.     

Nanoparticle‐Embedded Electrospun Fiber–Covered Stent to Assist Intraluminal Photodynamic Treatment of Oesophageal Cancer

Drug‐eluting stents (DESs) are promising candidates for treating human oesophageal cancer. However, the use of DESs to assist photodynamic therapy (PDT) of orthotopic oesophageal tumors is not yet demonstrated to the best of current knowledge. Herein, through an electrospinning technology it is shown that oxygen‐producing manganese dioxide nanoparticles are embedded into elelctrospun fibers, which are subsequently covered onto stents. Upon implantation, the nanoparticles are gradually released from the fibers and then diffuse into the nearby tumor tissue. Then, the hypoxic microenvironment can be effectively alleviated by reaction of MnO₂ with the endogenous H₂O₂ within the tumor. After demonstrating the excellent PDT efficacy of the stents in a conventional subcutaneous mouse tumor model, such stents are further used for PDT treatment in a rabbit orthotopic oesophageal cancer model by inserting an optical fiber into the tumor site. Greatly prolonged survival of rabbits is observed after such intraluminal PDT treatment. Taken together, this work shows that the fiber‐covered stent as a nanoparticle delivery platform can enable effective PDT as a noninvasive treatment method for patients with advanced‐stage oesophageal cancer.     

Characterization and in vivo evaluation of a bio-corrodible nitrided iron stent

A bio-corrodible nitrided iron stent was developed using a vacuum plasma nitriding technique. In the nitrided iron stents, the tensile strength, radial strength, stiffness and in vitro electrochemical corrosion rate were significantly increased compared with those of the control pure iron stent. To evaluate its performance in vivo, the deployment of the nitrided iron stents in juvenile pig iliac arteries was performed. At 3 or 6 months postoperatively, the stented vessels remained patent well; however, slight luminal loss resulting from intimal hyperplasia and relative stenosis of the stented vessel segment with piglets growth were observed by 12 months; no thrombosis or local tissue necrosis was found. At 1 month postoperatively, a nearly intact layer of endothelial cells formed on the stented vessel wall. Additionally, a decreased inflammation scoring, considerably corroded struts and corrosion products accumulation were seen. These findings indicate the potential of this nitrided iron stent as an attractive biodegradable stent.     

Design,Characterization, and 3D Printing of Cardiovascular Stents with Zero Poisson’s Ratio in Longitudinal Deformation

Inherent drawbacks associated with drug-eluting stents have prompted the development of bioresorbable cardiovascular stents. Additive manufacturing (3-dimentional (3D) printing) has been widely applied in medical devices. In this study, we develop a novel screw extrusion-based 3D printing system with a new designed mini-screw extruder to fabricate stents. A stent with a zero Poisson’s ratio (ZPR) structure is designed, and a preliminary monofilament test is conducted to investigate appropriate fabrication parameters. 3D-printed stents with different geometric structures are fabricated and analyzed by observation of the surface morphology. An evaluation of the mechanical properties and a preliminary biological evaluation of 3D-printed stents with different parameters are carried out. In conclusion, the screw extrusion-based 3D printing system shows potential for customizable stent fabrication.     

不同材料冠状动脉支架膨胀行为分析

冠状动脉支架作为经皮穿刺冠状动脉成形术中保持病变血管畅通的核心器件,其在手术过程中受球囊作用的扩张特性以及球囊撤出后的反弹行为对支架植入术的成功有着重要的影响.利用有限元的方法系统,建立专有支架单独膨胀和血管支架膨胀模型,分析了316L不锈钢和L605钴铬合金两种材料支架筋尺寸和支架扩张尺度的变化及血管对其膨胀行为的影响.结果显示,支架所选材料是决定支架膨胀行为的主要因素,L605材料支架所需的临界内压力及反弹行为明显大于316L不锈钢支架;材料一定时,增加支架筋的宽度或厚度提高支架迅速扩张临界内压力;支架轴向长度的变化只与结构和最终膨胀状态相关.有限元模拟对支架性能的评价和设计有一定指导意义.     

An integrated semicompliant balloon ultrasound catheter for quantitative feedback and image guidance during stent deployment

An integrated balloon ultrasound catheter prototype was designed to image from inside the balloon for real-time guidance during stent deployment. It was fabricated using a semicompliant balloon material (polyethylene) and a 20 MHz, 64-element circumferential ultrasound array. A commercial stent, nominally 4.4 mm in diameter and 12 mm in length, was used for a phantom study and placed along the length of the integrated balloon ultrasound catheter. A rubber phantom was created with an elastic modulus of 175 kPa with a 4.36 mm diameter lumen. Real-time balloon pressure measurements were recorded using a digital pressure sensor, and real-time radio-frequency (RF) data were captured as the balloon was inflated. The slope of the area-pressure ratio (APR) was compared to a reference measure of the balloon and stent expanded in water to determine a measure for optimal stent deployment. The results clearly indicate stent deployment at 11.1 atm using this metric. The APR slope could serve as quantitative feedback parameter for guiding stent deployment to reduce arterial injury and subsequent restenosis. After the stent deployment experiment, RF data were captured as the balloon catheter was moved along the length of the stent in pullback mode to confirm successful stent deployment. Ultimately, an integrated balloon ultrasound catheter could serve as a single catheter intervention device by providing real-time intravascular ultrasound (IVUS) imaging and quantitative feedback during stent deployment.     

Practicability and Limitations of Finite Element Simulation of the Dilation Behaviour of Coronary Stents

After first implantation of a metallic stent into cardiac vessels in 1986 stent implantation has become a standard technique for treatment of coronary heart disease. During implantation of balloon‐expandable stents, the structure of the stent undergoes high plastic deformation. Despite the fact, that stents are used for more than 15 years nearly no information about the mechanical and micro structural process during dilation are known. The present paper presents a detailed study and comparison of the experimental and the simulated expansion behaviour of metallic stents. Used material models are discussed and crystallographic details are presented. Dilation curves describe the behaviour of balloon‐expandable coronary stents. The dilation behaviour depends on both the materials properties and the design of the stent. A numerical simulation of the dilation process by means of FE is suitable. A comparison of the experimental measurement and the numerical simulation demonstrates, that a Cauchy stress‐strain material model should be used for numerical simulations. A local failure criterion is introduced, which considers void initiation as a criterion for mechanical failure.     

Development and characterization of a coronary polylactic acid stent prototype generated by selective laser melting

In-stent restenosis is still an important issue and stent thrombosis is an unresolved risk after coronary intervention. Biodegradable stents would provide initial scaffolding of the stenosed segment and disappear subsequently. The additive manufacturing technology Selective Laser Melting (SLM) enables rapid, parallel, and raw material saving generation of complex 3- dimensional structures with extensive geometric freedom and is currently in use in orthopedic or dental applications. Here, SLM process parameters were adapted for poly-l-lactid acid (PLLA) and PLLA-co-poly-ε-caprolactone (PCL) powders to generate degradable coronary stent prototypes. Biocompatibility of both polymers was evidenced by assessment of cell morphology and of metabolic and adhesive activity at direct and indirect contact with human coronary artery smooth muscle cells, umbilical vein endothelial cells, and endothelial progenitor cells. γ-sterilization was demonstrated to guarantee safety of SLM-processed parts. From PLLA and PCL, stent prototypes were successfully generated and post-processing by spray- and dip-coating proved to thoroughly smoothen stent surfaces. In conclusion, for the first time, biodegradable polymers and the SLM technique were combined for the manufacturing of customized biodegradable coronary artery stent prototypes. SLM is advocated for the development of biodegradable coronary PLLA and PCL stents, potentially optimized for future bifurcation applications.     

不同扩张尺度对非对称椎动脉支架力学性能影响的研究

在临床治疗中,不同尺寸的狭窄血管所需要支架扩张的尺度也不同,而支架的扩张尺度对其力学性能有着重要影响。利用有限元方法仿真模拟分析了三款不同支架的体外扩张过程,主要研究了结构相同时不同扩张尺度对支架力学性能的影响。结果显示：随着支架扩张直径的增大,支架的最大等效应力、轴向短缩率、扩张不均匀性及柔顺性能呈递增趋势,支撑刚度和静安全系数呈递减趋势;支架的径向回弹主要受到其材料和结构影响,扩张尺度并不起决定性作用;通过与实验结果相比对,理论值与实验值结果吻合较好,误差在7%以内,验证了有限元模拟的准确性及合理性;利用动物实验对支架治疗效果进行验证,表明了支架的植入治疗是安全且有效的。综合考虑各因素影响,支架的治疗效果受支架扩张尺度的影响较大,这为临床治疗的顺利实施提供了良好的理论依据。     

Electrografting of a biodegradable layer as a primer adhesion coating onto a metallic stent: in vitro and in vivo evaluations

Drug-eluting stents have been developed to reduce the risk of restenosis after angioplasty. To facilitate the adhesion of a poly(lactic acid) (PLA) overlayer loaded with rapamycin (20 wt%), a biodegradable macromonomer based on poly(lactic acid) (HEMA-PLA) was grafted onto the metallic stent by electrografting in a one-step reaction involving the immobilization of aryl diazonium onto the metal followed by an in situ surface electro-polymerization. The HEMA-PLA coating was chemically characterized. Mechanical performance during stent expansion was tested. Morphology examinations showed a strong adhesion of PLA topcoat in the presence of the electrografted layer. Biocompatibility and degradation of the coating were studied in vitro and in vivo in rabbit iliac arteries. These 28 days implantations resulted in a minimal inflammatory process with a partial degradation of the coating. These results suggest that this kind of anchoring of a biodegradable layer shows great potential for drug-eluting stents.     

Development of a polymer stent with shape memory effect as a drug delivery system

The article presents a new concept for vascular endoprothesis (stent). Almost all commercially available stents are made of metallic materials. A common after effect of stent implantation is restenosis. Several studies on metal stents coated with drug show, that the use of a drug delivery system may reduce restenosis. The purpose of this work is to develop a new stent for the drug delivery application. The shape memory properties of thermoplastic polyurethane allow to design a new fully polymeric self-expandable stent. The possibility to use the stent as a drug delivery system is described.     

Preparation and characterization of rapamycin-loaded PLGA coating stent

In this study, using polylactic acid-co-glycolic acid (PLGA) with a molecular weight of 95,800 Da as drug carrier, three dose (low, moderate, high) rapamycin-eluting stents and the corresponding coating films were prepared. The pre- and post-expansion morphology of the rapamycin-eluting stent was examined by scanning electron microscopy (SEM), indicating that the coating was very smooth and uniform. The coating had the ability to withstand the compressive and tensile strains imparted without cracking from the stent during expansion process. There were many voids on stent coating surface after released for 18 days in release medium. The thermodynamics data of the stent coating film measured by differential scanning calorimetry (DSC) showed a lack of measurable solubility of rapamycin in the PLGA matrix. The release behavior of rapamycin from stent surface had a two phase release profile with a burst release period of about 2 days, followed by a sustained and slow release phase. The mass loss behavior of PLGA appeared linear throughout most of the degradation period, corresponding to an approximately constant mass loss rate. The platelet adhesion tests showed that the rapamycin-eluting films may have a good blood compatibility compared with control samples. Take into these results account, this novel rapamycin-eluting may be a good candidate to resolve in-stent restenosis.     

Physicochemical characterisation and biological evaluation of polyvinylpyrrolidone-iodine engineered polyurethane (Tecoflex<Superscript>®</Superscript>)

Bacterial adhesion and encrustation are the known causes for obstruction or blockage of urethral catheters and ureteral stents, which often hinders their effective use within the urinary tract. In this in vitro study, polyvinylpyrrolidone-iodine (PVP-I) complex modified polyurethane (Tecoflex^®) systems were created by physically entrapping the modifying species during the reversible swelling of the polymer surface region. The presence of the PVP-I molecules on this surfaces were verified by ATR-FTIR, AFM and SEM-EDAX analysis, while wettability of the films was investigated by water contact angle measurements. The modified surfaces were investigated for its suitability as a urinary tract biomaterial by comparing its lubricity and ability to resist bacterial adherence and encrustation with that of base polyurethane. The PVP-I modified polyurethane showed a nanopatterned surface topography and was highly hydrophilic and more lubricious than control polyurethane. Adherence of both the gram positive Staphylococcus aureus (by 86%; **P < 0.01) and gram-negative Pseudomonas aeruginosa (by 80%; *P < 0.05) was significantly reduced on the modified surfaces. The deposition of struvite and hydroxyapatite the major components of urinary tract encrustations were significantly less on PVP-I modified polyurethane as compared to base polyurethane, especially reduction in hydroxyapatite encrustation was particularly marked. These results demonstrated that the PVP-I entrapment process can be applied on polyurethane in order to reduce/lower complications associated with bacterial adhesion and deposition of encrustation on polyurethanes.     

Accelerated endothelialization with a polymer-free sirolimus-eluting antibody-coated stent

Drug-eluting stents have shown an impressive reduction of in-stent restenosis for many years. However, stent thrombosis due to incomplete/late endothelialization has raised major safety concerns. To overcome these problems, we developed for the first time a polymer-free sirolimus-eluting antibody-coated stent (PFSEACS) by combining polymer free and endothelial progenitor cell-capture pro-healing approaches. In the first phase, the stents were prepared by loading sirolimus on the porous outer stent surface and directly fixing the anti-CD34 antibodies without any medium carriers on the blood contacting surface. The dose and elution of sirolimus, the amount and stability of anti-CD34 antibody immobilization, and the rate of CD34+ cell capture were evaluated. In the second phase, the stents were validated in an animal model of coronary arteries in pigs. The stent was observed to start collecting endothelial progenitor cells ~2 h after stent implantation and exhibited greatly enhanced endothelialization while maintaining an excellent anti-restenosis activity comparable to the polymer-free sirolimus-eluting stents. Overall, both in vitro and in vivo evaluations indicated that novel PFSEACSs exhibited facilitated endothelialization with excellent anti-restenosis activity and thus should merit further clinical studies.     

Novel paclitaxel-coated angioplasty balloon catheter based on cetylpyridinium salicylate: Preparation,characterization and simulated use in an in vitro vessel model

Drug-coated balloons (DCB), which have emerged as therapeutic alternative to drug-eluting stents in percutaneous cardiovascular intervention, are well described with regard to clinical efficiency and safety within a number of clinical studies. In vitro studies elucidating the correlation of coating method and composition with DCB performance are however rare but considered important for the understanding of DCB requirements and the improvement of established DCB. In this context, we evaluated the applicability of a pipetting, dip-coating, and spray-coating process for the establishment of DCB based on paclitaxel (PTX) and the ionic liquid cetylpyridinium salicylate (Cetpyrsal) as novel innovative additive in three different compositions. Among tested methods and compositions, the pipetting process with 50 wt.% PTX resulted in most promising coatings as drug load was less controllable by the other processes and higher PTX contents led to considerable drug crystallization, as visualized by electron microscopy, accelerating PTX loss during short-term elution. Applying these conditions, homogeneous coatings could be applied on balloon catheter, whose simulated use in an in vitro vessel model revealed percental drug losses of 36 and 28% during transit and percental drug transfers of 12 and 40% under expansion for coatings applied in expanded and folded balloon condition, respectively. In comparison to literature values, these results support the high potential of Cetpyrsal as novel DCB matrix regarding low drug loss and efficient drug transfer.