Static and Flow Conditions: Endothelial Cell Migration onto Metal Stent Surfaces.

Restenosis associated with intimal hyperplasia and thrombosis at sites of balloon angioplasty or stent placement remains an important clinical problem. It is likely that loss or damage to the arterial endothelium associated with these interventional procedures as well as the rate of its restoration plays a critical role in the extent of restenosis. Migration of arterial endothelial cells from adjacent intact endothelium is the predominant source of cells involved in re-endothelialization of the injured site. In this paper, we review the influence of hemodynamics on endothelial cell migration, both in vivo and in vitro. In addition, we present recent in vitro studies demonstrating the importance of the nature of metal substrates in modulating endothelial cell migration rate. Finally, we review the cellular and molecular mechanisms likely involved in governing endothelial cell migration, and relate them to a possible scenario of endothelial response to injury at sites of arterial intervention. Understanding the important factors regulating endothelial migration may provide insights that will ultimately lead to methods to accelerate endothelial healing and reduce the occurrence of arterial restenosis.

Biological effect of microengineered grooved stents on strut healing: a randomised OCT-based comparative study in humans.

OBJECTIVE: To evaluate the biological effect of microengineered stent grooves (MSG) on early strut healing in humans by performing optical coherence tomography (OCT) analysis 3 weeks following the implantation. BACKGROUND: In the experimental setting, MSG accelerate endothelial cell migration and reduce neointimal proliferation compared with bare metal stent (BMS). METHODS: A total of 37 patients undergoing percutaneous coronary intervention with de novo coronary lesions were randomly assigned to either MSG (n=19) or an identical BMS controls (n=18). All patients underwent OCT imaging at 3 weeks. A total of 7959 struts were included in the final analysis. RESULTS: At 3 weeks following stent implantation, almost all struts analysed (~97%) had evidence of tissue coverage. The percentage of partially covered struts was comparable between both groups. However, the percentage of fully embedded struts was higher in the BMS group (81.22%, 49.75-95.52) compared with the MSG group (74.21%, 58.85-86.38). The stent-level analysis demonstrated reduction in neointimal formation (neointimal hyperplasia area and volume reduction of ~14% and ~19%, respectively) in the MSG versus the BMS group. In the strut-level analysis, an even greater reduction (~22% in neointimal thickness) was seen in the MSG group. Layered neointimal was present in ~6% of the OCT frames in the BMS group while it was not present in the MSG group. CONCLUSIONS: MSG induced a more homogeneous and predictable pattern of surface healing in the early stages following stent implantation. The biological effect of MSG on stent healing has the potential to improve the safety profile of current generation drug-eluting stents. CLASSIFICATIONS: BMS, OCT, clinical trials.

Role of stent design and coatings on restenosis and thrombosis.

More than 15 years have passed since stent technology was introduced by Sigwart et al. [U. Sigwart, J. Puel, V. Mirkovitch, F. Joffe, et al. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N. Engl. J. Med. 316 (1987) 701-706.] among interventional cardiologists. Recently drug eluting stents have assumed dominance in the interventional world as positive trial results revealed their efficacy for preventing restenosis. Stent design, delivery-vehicle materials, and drug properties affect the function of these stents. Stainless steel stents with tubular and multicellular design have proven superior to coil or hybrid stent models. This chapter describes stents which have subtle influences of modular design, metal coverage, strut thickness, strut shape, surface smoothness, and coating materials like an alloy composition.

A model system to assess key vascular responses to biomaterials.

PURPOSE: To establish a reproducible laboratory test to evaluate prospective vascular biomaterials with respect to their thromboinflammatory properties by examining fibrinogen, platelet, and monocyte binding. Endothelial migration onto these surfaces was used as an index of vascular healing. METHODS: To evaluate biomaterials for potential thrombogenicity and inflammation, binding assays of radiolabeled human fibrinogen, platelets, and monocytes were performed on standard pieces of vascular biomaterials, including metals and polymeric and ceramic-coated materials. Using an established in vitro endothelial cell migration model, the relative migration rate of cultured human aortic endothelial cells onto these vascular biomaterials was measured and compared. The fibrinogen, platelet, and monocyte binding results were combined along with the migration results to create an overall score of biocompatibility. RESULTS: A significant direct relation of platelet and monocyte binding to the amount of adsorbed fibrinogen was observed. In contrast, migration rates of cultured human aortic endothelial cells onto the same biomaterial surfaces were found to be inversely related the amount of bound fibrinogen. Among the materials tested, stainless steel received the highest score of biocompatibility, while turbostratic carbon scored the lowest. CONCLUSIONS: Fibrinogen, platelet, and monocyte binding levels, as well as endothelial migration rates onto vascular material surfaces, provide a basis for evaluating thrombogenicity, inflammatory potential, and endothelialization in the laboratory prior to in vivo testing.

Intravascular stents in the last and the next 10 years.

The first balloon-expandable coronary stent was approved "for the prevention of restenosis" in 1994, the same year that the Journal of Endovascular Therapy was inaugurated. Since then, the development of the stent has paralleled the evolution of endovascular intervention as a new specialty. Innovators have pushed to explore new and varied stent applications outside the coronary arteries. Carotid stenting, transjugular intrahepatic portocaval shunts, and covered stents are a few of these new applications that have now become commonplace. Dozens of stent designs and several new materials have been tested to solve the problem of in-stent restenosis, but it is the drug-eluting stent (DES) that has emerged as the most promising, at least in the coronary arteries. However, the benefits of DES technology are not likely to be effective in the more pervasive forms of in-stent restenosis, such as encountered in the femoropopliteal segment. In the future, technologies aimed at stimulating rather than inhibiting tissue response to an implant may be part of the next wave of developments, as we take aim against the poor and/or slow tissue incorporation that manifests as leaks and dislodgement. In the superficial femoral artery, for example, mechanical stresses that cause fractures and dislocations may be addressed by using a very flexible endovascular device with a tissue-friendly inner surface that promotes rapid stent endothelialization to counter the biological effects of motion and microtrauma. The rapidly developing fields of nanotechnology, microelectronics, and advanced materials technology will enable the surface engineer to design molecular-specific surfaces for a new generation of vascular devices. Interactive implantable or injectable microdevices aimed at providing specific information upon demand from an external source will revolutionize disease prevention, as emphasis shifts toward monitoring cardiovascular risk exposure. There is no doubt that during the next 10 years, we will witness impressive technological progress in the field of cardiovascular implantable devices.

Influence of stent design and material composition on procedure outcome.

Although intravascular stents have received widespread application, significant limitations remain. In stent restenosis, the most pervasive problem affecting stents, is related in part to technical aspects of the device. Design features of the stent that influence outcome have been identified and optimized for improved performance. The influence of stent materials on critical aspects of healing, such as thrombotic, inflammatory, and hyperplastic responses, are less well understood. For this reason, significant progress in this area is lacking. Current stents have significant contamination with industrial impurities on the surface and in the bulk. This fact adds to the difficulties in interpreting the biologic reaction of the host to the device. Better understanding of the basic biologic interactions is the path to significant improvement.

Tratamiento endoluminal de los aneurismas de aorta / Intraluminal treatment in abdominal aortic aneurysms

Debido al aumento de la población añosa, los cirujanos vasculares se encuentran con mayor frecuencia con pacientes portadores de aneurismas de aorta abdominal que tienen múltiples y severas enfermedades asociadas. El presente estudio se refiere a la experiencia animal y a los primeros casos clínicos de un nuevo tratamiento de los aneurismas que es la inserción retrógrada de una prótesis vascular fijada a "stends" metálicos que se implantan a través de un balón que al inflarse expande al "stends" y lo fija a la pared aórtica. En el trabajo experimental se crearon aneurismas de aorta en perros reemplazando la aorta infrarrenal con una prótesis de dacron en forma de aneurisma; después de cuatro semanas se excluye el aneurisma desde la luz implantando desde la arteria femoral, en forma retrógrada la combinación de "stend" y prótesis. Desde setiembre de 1990 se implantaron 6 pacientes. Un paciente debió ser operado después de implantar la prótesis demasiado alejada de las arterias renales. Todos los pacientes evolucionaron favorablemente