Simulated Bench Testing to Evaluate the Mechanical Performance of New Carotid Stents

Our group recently developed a novel covered carotid stent that can prevent emboli while preserving the external carotid artery (ECA) branch blood flow. However, our recent in vitro side‐branch ECA flow preservation tests on the covered stents revealed the need for further stent frame design improvements, including the consideration to crimp the stent to a low profile for the delivery of the stent system and having bigger cells. Hence, the current work aims to design new bare metal stents with bigger cell size to improve the crimpability and to accommodate more slits so that the side‐branch flow could be further increased. Three new stent designs were analyzed using finite element analysis and benchmarked against two commercially available carotid stents in terms of their mechanical performances such as crimpability, radial strength, and flexibility. Results indicated that the new bare metal stent designs matched well against the commercial stents. Hence our new generation covered stents based on these designs can be expected to perform better in side‐branch flow preservation without compromising on their mechanical performances.     

腹主动脉瘤信号传导相关基因的研究

目的：研究细胞信号传导基因在腹主动脉瘤和正常主动脉的差异表达，探讨其与腹主动脉瘤发生的关系。方法：应用基因芯片技术检测腹主动脉瘤和正常主动脉信号传导相关基因的表达，筛选出差异表达显著的基因，从RNA和蛋白质水平作进一步的分子生物学实验。结果：发现腹主动脉瘤差异表达的信号传导基因45条，在动脉瘤组织中表达上调基因为28条，表达下调基因17条。对其中MAPK信号系统的进一步实验发现ASK1、ERK1等基因异常表达，均在主动脉中层有蛋白质表达。结论：信号传导相关基因的差异表达可能与腹主动脉瘤的发生有关。     

用基因表达谱芯片筛选原发性下肢静脉曲张相关基因的研究

目的运用基因表达谱芯片研究原发性下肢静脉曲张基因表达谱的变化。方法选取原发性下肢静脉曲张患者隐 股交界瓣膜区静脉 5条 ,取 5条正常静脉作对照。抽提总RNA、纯化mRNA、反转录制备杂交探针 ,应用含有 4 0 96种人类基因全长cDNA的表达谱芯片进行差异表达谱分析 ,随后应用反转录PCR验证部分差异表达基因。结果曲张大隐静脉瓣膜区表达谱中差异表达基因共有 16 8条 ,上调基因 96条 ,下调基因 72条 ;5例标本均差异表达的基因共 39条 ,其中上调2 8条 ,下调 11条 ;多条细胞凋亡相关基因、细胞信号和传递蛋白基因、原癌基因和抑癌基因等均有差异表达 ;反转录PCR证实caspase 9及MAP3K基因及其蛋白产物在曲张静脉中差异表达。 结论应用基因表达谱芯片筛选致病相关基因 ,可能为下肢静脉曲张的发病机制研究提供新思路。     

Ⅲ型胶原在腹主动脉瘤及正常主动脉中表达的研究

目的研究Ⅲ型胶原 (typeⅢcollagen)在腹主动脉瘤 (abdominalaorticaneurysm ,AAA)与正常主动脉中的表达差异。方法应用逆转录 聚合酶链反应 (RT PCR)方法研究 5例AAA标本和 3例正常主动脉标本的Ⅲ型胶原的表达情况 ,并应用免疫组织化学的方法研究Ⅲ型胶原在AAA和正常主动脉中的差异。结果AAA与正常动脉 (NA)组织相比 ,其Ⅲ型胶原的表达明显增强 ,AAA/NA为7 2 5 1(P <0 .0 1) ,而免疫组化则证实在AAA组织中 ,Ⅲ型胶原粗大、紊乱 ,在正常组织中则比较规整。结论Ⅲ型胶原在AAA中的表达比正常主动脉明显升高 ,形态上亦较正常主动脉粗大紊乱     

Covered Stent Membrane Design for Treatment of Atheroembolic Disease at Carotid Artery Bifurcation and Prevention of Thromboembolic Stroke: An In Vitro Experimental Study

In this study, a polymeric membrane has been designed and developed for carotid stents to prevent detachment of emboli from the arterial wall and subsequent stroke, while maintaining side‐branch flow. Prototypes of different geometrical design parameters have been fabricated and their performance has been evaluated in vitro under physiological pulsatile flow condition in a life‐size silicone anastomotic model of carotid artery bifurcation. These evaluations include both quantitative and qualitative experimental (in vitro) assessments of emboli prevention capability, side‐branch flow preservation, and flow visualization. The covered stents with the novel membrane demonstrated significantly higher emboli prevention capability than the corresponding bare nitinol stent as well as some earlier related designs, while preserving more than 93% of the original flow of the external carotid artery (ECA). Flow in the ECA through these covered stents was uniform without evidence of undesirable flow recirculation or retrograde flow that might predispose the vessel wall to intimal thickening and atherosclerotic plaque formation. This study demonstrated the potential of these novel covered stent designs for the treatment of carotid atherosclerotic stenosis and prevention of late embolic stroke. However, further in vivo investigations of biological effects and mechanical performance of this covered stent design (e.g., its thrombogenicity potential and biocompatibility) are warranted.     

钙整合素结合蛋白-1在OX-LDL抑制小鼠巨噬细胞迁移中的作用研究

目的探讨钙整合素结合蛋白-1(calcium-and integrin-binding protein-1,CIB1)在氧化低密度脂蛋白(OX-LDL)抑制巨噬细胞迁移中的作用。方法通过RNA干扰技术沉默小鼠巨噬细胞CIB1表达,再与OX-LDL共孵育,观察小鼠巨噬细胞迁移及细胞延展情况。结果巨噬细胞转染CIB1 siRNA 24～72 h后,巨噬细胞CIB1蛋白表达被显著抑制,沉默CIB1能显著增加巨噬细胞迁移数量及巨噬细胞延展能力。结论 CIB1在OX-LDL抑制巨噬细胞迁移的胞内调控机理中起着重要作用。     

The effect of collagen I mimetic peptides on mesenchymal stem cell adhesion and differentiation,and on bone formation at hydroxyapatite surfaces

Integrin-binding peptides increase cell adhesion to naive hydroxyapatite (HA), however, in the body, HA becomes rapidly modified by protein adsorption. Previously we reported that, when combined with an adsorbed protein layer, RGD peptides interfered with cell adhesion to HA. In the current study we evaluated mesenchymal stem cell (MSC) interactions with HA disks coated with the collagen-mimetic peptides, DGEA, P15 and GFOGER. MSCs adhered equally well to disks coated with DGEA, P15, or collagen I, and all three substrates, but not GFOGER, supported greater cell adhesion than uncoated HA. When peptide-coated disks were overcoated with proteins from serum or the tibial microenvironment, collagen mimetics did not inhibit MSC adhesion, as was observed with RGD, however neither did they enhance adhesion. Given that activation of collagen-selective integrins stimulates osteoblastic differentiation, we monitored osteocalcin secretion and alkaline phosphatase activity from MSCs adherent to DGEA or P15-coated disks. Both of these osteoblastic markers were upregulated by DGEA and P15, in the presence and absence of differentiation-inducing media. Finally, bone formation on HA tibial implants was increased by the collagen mimetics. Collectively these results suggest that collagen-mimetic peptides improve osseointegration of HA, most probably by stimulating osteoblastic differentiation, rather than adhesion, of MSCs.     

The Development of Polymeric Cardiovascular Collagen Prostheses

In an attempt to develop a long-lasting, non-thrombogenic, collagen cardiovascular prosthesis this laboratory has sequentially evaluated a series of modified collagen structures treated as polymers. Bovine arteries and human umbilical cords have been subjected to various chemical modifications and grouped as follows: 1.) fresh, untreated vessels, 2.) commercially available dialdehyde starch tanned grafts, 3.) ficin digested (muscle and elastin removed) vessels, 4.) ficin digested negatively charged, untanned grafts, 5.) ficin digested, negatively charged, dialdehyde starch tanned grafts, 6.) ficin digested, oxidized carboxymethylcellulose tanned grafts, 7.) ficin digested, glutaraldehyde tanned, protein cross-linked, negatively charged grafts. The aim in each case was to create a specific recurrent stereo specific electrochemical charge at the blood-tissue interface. These tubular grafts were then evaluated in several positions following canine implantation. The results confirmed that the single most important factor in assuring long-term patency and function was provision of a uniform, highly covalently bonded, glutaraldehyde tanned, negative surface charge. Unmodified grafts thrombosed and then became calcified or dissolved within a short period of time. Techniques for evaluation included resistance to thrombosis and observed characteristics of the grafts at periodic intervals of 1 second, 2 hours, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months and longer. Upon removal, each of these grafts was inspected, photographed, tested for tensile strength, and observed by light and scanning electron microscopy. In summary, the most satisfactory graft was the ficin digested, glutaraldehyde tanned, negatively charged prosthesis. Subsequently, these grafts were prepared for implantation in humans. At this time approximately 69 segments have been implanted in 35 patients. The majority (36) have been implanted in the femoral-popliteal position. Axillofemoral, femorofemoral, aortorenal, peripheral arteriovenous, coronary, iliopopliteal and femoroperoneal bypasses were also performed. These results have been compared with gas endarterectomy, saphenous vein bypass (conventional), and bovine heterograft prostheses in similar implantation sites. Follow-up of this group to two years reveals patency approaching that of autogenous saphenous vein grafts and surpassing that of conventional bovine heterografts. These data suggest that collagen with chemical and surface charge modification may lead to a new generation of biological cardiovascular prostheses exhibiting improved performance characteristics and freedom from thrombosis.