Increased endothelial and vascular smooth muscle cell adhesion on nanostructured titanium and CoCrMo

In the body, vascular cells continuously interact with tissues that possess nanostructured surface features due to the presence of proteins (such as collagen and elastin) embedded in the vascular wall. Despite this fact, vascular stents intended to restore blood flow do not have nanoscale surface features but rather are smooth at the nanoscale. As the first step towards creating the next generation of vascular stent materials, the objective of this in vitro study was to investigate vascular cell (specifically, endothelial, and vascular smooth muscle cell) adhesion on nanostructured compared with conventional commercially pure (cp) Ti and CoCrMo. Nanostructured cp Ti and CoCrMo compacts were created by separately utilizing either constituent cp Ti or CoCrMo nanoparticles as opposed to conventional micron-sized particles. Results of this study showed for the first time increased endothelial and vascular smooth muscle cell adhesion on nanostructured compared with conventional cp Ti and CoCrMo after 4 hours' adhesion. Moreover, compared with their respective conventional counterparts, the ratio of endothelial to vascular smooth muscle cells increased on nanostructured cp Ti and CoCrMo. In addition, endothelial and vascular smooth muscle cells had a better spread morphology on the nanostructured metals compared with conventional metals. Overall, vascular cell adhesion was better on CoCrMo than on cp Ti. Results of surface characterization studies demonstrated similar chemistry but significantly greater root-mean-square (rms) surface roughness as measured by atomic force microscopy (AFM) for nanostructured compared with respective conventional metals. For these reasons, results from the present in vitro study provided evidence that vascular stents composed of nanometer compared with micron-sized metal particles (specifically, either cp Ti or CoCrMo) may invoke cellular responses promising for improved vascular stent applications.     

Vascular Gene Transfer from Metallic Stent Surfaces Using Adenoviral Vectors Tethered through Hydrolysable Cross-linkers

In-stent restenosis presents a major complication of stent-based revascularization procedures widely used to re-establish blood flow through critically narrowed segments of coronary and peripheral arteries. Endovascular stents capable of tunable release of genes with anti-restenotic activity may present an alternative strategy to presently used drug-eluting stents. In order to attain clinical translation, gene-eluting stents must exhibit predictable kinetics of stent-immobilized gene vector release and site-specific transduction of vasculature, while avoiding an excessive inflammatory response typically associated with the polymer coatings used for physical entrapment of the vector. This paper describes a detailed methodology for coatless tethering of adenoviral gene vectors to stents based on a reversible binding of the adenoviral particles to polyallylamine bisphosphonate (PABT)-modified stainless steel surface via hydrolysable cross-linkers (HC). A family of bifunctional (amine- and thiol-reactive) HC with an average t_1/2 of the in-chain ester hydrolysis ranging between 5 and 50 days were used to link the vector with the stent. The vector immobilization procedure is typically carried out within 9 hr and consists of several steps: 1) incubation of the metal samples in an aqueous solution of PABT (4 hr); 2) deprotection of thiol groups installed in PABT with tris(2-carboxyethyl) phosphine (20 min); 3) expansion of thiol reactive capacity of the metal surface by reacting the samples with polyethyleneimine derivatized with pyridyldithio (PDT) groups (2 hr); 4) conversion of PDT groups to thiols with dithiothreitol (10 min); 5) modification of adenoviruses with HC (1 hr); 6) purification of modified adenoviral particles by size-exclusion column chromatography (15 min) and 7) immobilization of thiol-reactive adenoviral particles on the thiolated steel surface (1 hr). This technique has wide potential applicability beyond stents, by facilitating surface engineering of bioprosthetic devices to enhance their biocompatibility through the substrate-mediated gene delivery to the cells interfacing the implanted foreign material.     

A quantitative study on magnesium alloy stent biodegradation

Insufficient scaffolding time in the process of rapid corrosion is the main problem of magnesium alloy stent (MAS). Finite element method had been used to investigate corrosion of MAS. However, related researches mostly described all elements suffered corrosion in view of one-dimensional corrosion. Multi-dimensional corrosions significantly influence mechanical integrity of MAS structures such as edges and corners. In this study, the effects of multi-dimensional corrosion were studied using experiment quantitatively, then a phenomenological corrosion model was developed to consider these effects. We implemented immersion test with magnesium alloy (AZ31B) cubes, which had different numbers of exposed surfaces to analyze differences of dimension. It was indicated that corrosion rates of cubes are almost proportional to their exposed-surface numbers, especially when pitting corrosions are not marked. The cubes also represented the hexahedron elements in simulation. In conclusion, corrosion rate of every element accelerates by increasing corrosion-surface numbers in multi-dimensional corrosion. The damage ratios among elements with the same size are proportional to the ratios of corrosion-surface numbers under uniform corrosion. The finite element simulation using proposed model provided more details of changes of morphology and mechanics in scaffolding time by removing 25.7% of elements of MAS. The proposed corrosion model reflected the effects of multi-dimension on corrosions. It would be used to predict degradation process of MAS quantitatively.     

药物洗脱支架植入术与冠状动脉旁路移植术治疗冠心病多支病变伴糖尿病患者的临床效果分析

目的:比较药物洗脱支架(DES)植入术及冠状动脉旁路移植术(CABG)治疗冠心病多支病变伴糖尿病患者的近期及远期临床疗效。方法:回顾性分析2014年1月~2016年10月在哈尔滨医科大学附属第一医院经冠状动脉造影证实为多支血管病变并伴有糖尿病的患者186例,根据血运重建方式的不同分为DES组及CABG组,随访50.5±14.3个月,观察两组患者住院期间及随访期主要不良心脑血管事件(包括非致死心肌梗死、脑卒中、再次血运重建、全因死亡)的发生情况。结果:在所有入选患者中,DES组有更多双支病变(P0.05),CABG组三支病变较多(P0.05),两组在完全血运重建方面无显著性差异(P0.05)。住院期间,CABG组死亡2例(2.3%),DES组死亡1例(1.0%),死亡率比较无统计学意义(P0.05)。两组均未出现非致死性心肌梗死、脑卒中、再次血运重建。出院后对186例入选患者随访,其中失访11例(DES组5例,CABG组6例)。随访期间CABG组发生非致死性心肌梗死1例(1.3%)、脑卒中6例(7.5%)、全因死亡10例(12.5%),DES组发生非致死性心肌梗死5例(5.3%)、脑卒中3例(3.2%)、全因死亡9例(9.5%),两组间比较差异无统计学意义(P0.05);而CABG组再次血运重建2例(2.5%),DES组15例(15.8%),两组比较差异具有统计学意义(P0.01)。结论:行DES置入术或CABG术治疗冠心病多支病变伴糖尿病患者,住院期间主要心脑血管不良事件发生率、远期非致死性心肌梗死、脑卒中、全因死亡发生情况均无显著性差异,但DES组再次血运重建率明显升高,可能与糖尿病患者较高的再狭窄率有关。     

Enhanced endothelial cell density on NiTi surfaces with sub-micron to nanometer roughness

The shape memory effect and superelastic properties of NiTi (or Nitinol, a nickel-titanium alloy) have already attracted much attention for various biomedical applications (such as vascular stents, orthodontic wires, orthopedic implants, etc). However, for vascular stents, conventional approaches have required coating NiTi with anti-thrombogenic or antiinflammatory drug-eluting polymers which as of late have proven problematic for healing atherosclerotic blood vessels. Instead of focusing on the use of drug-eluting anti-thrombogenic or anti-inflammatory proteins, this study focused on promoting the formation of a natural antithrombogenic and anti-inflammatory surface on metallic stents: the endothelium. In this study, we synthesized various NiTi substrates with different micron to nanometer surface roughness by using dissimilar dimensions of constituent NiTi powder. Endothelial cell adhesion on these compacts was compared with conventional commercially pure (cp) titanium (Ti) samples. The results after 5 hrs showed that endothelial cells adhered much better on fine grain (< 60 microm) compared with coarse grain NiTi compacts (< 100 microm). Coarse grain NiTi compacts and conventional Ti promoted similar levels of endothelial cell adhesion. In addition, cells proliferated more after 5 days on NiTi with greater sub-micron and nanoscale surface roughness compared with coarse grain NiTi. In this manner, this study emphasized the positive pole that NiTi with sub-micron to nanometer surface features can play in promoting a natural anti-thrombogenic and anti-inflammatory surface (the endothelium) on a vascular stent and, thus, suggests that more studies should be conducted on NiTi with sub-micron to nanometer surface features.     

药物涂层支架与金属裸支架治疗ST段抬高型心肌梗死的临床价值比较

目的:评价药物涂层支架(DES)与金属裸支架(BMS)在急性心肌梗死患者中应用的安全性和有效性。方法:选择2003年1月-2010年12月,在我院确诊的急性ST段抬高型心肌梗死(STEMI)167例患者,其中使用BMS 65例,DES 102例。对比分析两组患者住院期间和出院后1年内的主要心血管或脑血管事件(MAACE)的发生情况及支架内血栓形成的发生率。结果:至随访结束,BMS组有1例患者猝死,5例出现复发心绞痛。DES组有1例突发急性左心衰后死亡,1例复发心绞痛和1例发生亚急性支架内血栓。结论:DES应用于STEMI具有较好的安全性,其术后MAACE发生率较BMS低。     

Modelling intravascular delivery from drug-eluting stents with biodurable coating: investigation of anisotropic vascular drug diffusivity and arterial drug distribution

In-stent restenosis occurs in coronary arteries after implantation of drug-eluting stents with non-uniform restenosis thickness distribution in the artery cross section. Knowledge of the spatio-temporal drug uptake in the arterial wall is useful for investigating restenosis growth but may often be very expensive/difficult to acquire experimentally. In this study, local delivery of a hydrophobic drug from a drug-eluting stent implanted in a coronary artery is mathematically modelled to investigate the drug release and spatio-temporal drug distribution in the arterial wall. The model integrates drug diffusion in the coating and drug diffusion with reversible binding in the arterial wall. The model is solved by the finite volume method for both high and low drug loadings relative to its solubility in the stent coating with varied isotropic–anisotropic vascular drug diffusivities. Drug release profiles in the coating are observed to depend not only on the coating drug diffusivity but also on the properties of the surrounding arterial wall. Time dependencies of the spatially averaged free- and bound-drug levels in the arterial wall on the coating and vascular drug diffusivities are discussed. Anisotropic vascular drug diffusivities result in slightly different average drug levels in the arterial wall but with very different spatial distributions. Higher circumferential vascular diffusivity results in more uniform drug loading in the upper layers and is potentially beneficial in reducing in-stent restenosis. An analytical expression is derived which can be used to determine regions in the arterial with higher free-drug concentration than bound-drug concentration.     

骨科保护支架在胫腓骨骨折患者术后护理中的应用效果

目的:探讨骨科保护支架在胫腓骨骨折患者术后护理中的应用效果。方法:选择30例胫腓骨骨折术后患者为研究对象,采用随机数字表法分为观察组和对照组各15例,对照组在术后用软枕抬高下肢,观察组在术后采用自制的骨科保护支架抬高下肢。比较两组肿胀程度与疼痛评分、关节功能、并发症、满意度。结果:肿胀程度与疼痛程度:术后2周时,观察组患肢肿胀消退时间、VAS评分明显低于对照组,Ⅰ度肿胀、轻度疼痛明显高于对照组(t/x2=6.587~16.861,P0.05);关节功能:术后2周时,观察组Lyaholm评分、关节活动度(Range of motion,ROM)、舒适度均明显高于对照组(t=5.155~15.676,P0.05);并发症:观察组并发症(6.67%)显著低于对照组(20.00%)(x2=7.988,P0.05);满意度:观察组满意度93.33%明显高于对照组73.33%(x2=6.975,P0.05)。结论:骨科保护支架能早期消除患肢肿胀,减轻疼痛程度,改善关节功能,提高患者满意度。     

Nanoparticulate carriers for the treatment of coronary restenosis

The current treatment for coronary restenosis following balloon angioplasty involves the use of a mechanical or a drug-eluting stent. Despite the high usage of commercially-available drug-eluting stents in the cardiac field, there are a number of limitations. This review will present the background ofrestenosis, go briefly into the molecular and cellular mechanisms of restenosis, the use of mechanical stents in coronary restenosis, and will provide an overview of the drugs and genes tested to treat restenosis. The primary focus of this article is to present a comprehensive overview on the use of nanoparticulate delivery systems in the treatment of restenosis both in-vitro and in-vivo. Nanocarriers have been tested in a variety of animal models and in human clinical trials with favorable results. Polymer-based nanoparticles, liposomes, and micelles will be discussed, in addition to the findings presented in the field of cardiovascular drug targeting. Nanocarrier-based delivery presents a viable alternative to the current stent based therapies.