Stable and Thin-Polymer-Based Modification of Neurovascular Stents with 2-Methacryloyloxyethyl Phosphorylcholine Polymer for Antithrombogenicity.

The advent of intracranial stents has revolutionized the endovascular treatment of cerebral aneurysms. The utilization of stents has rendered numerous cerebral aneurysm amenable to endovascular treatment, thereby obviating the need for otherwise invasive open surgical options. Stent placement has become a mainstream approach because of its safety and efficacy. However, further improvements are required for clinically approved devices to avoid the frequent occurrence of thrombotic complications. Therefore, controlling the thrombotic complications associated with the use of devices is of significant importance. Our group has developed a unique stent coated with a 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer. In this study, the surface characteristics of the polymer coating were verified using X-ray photoelectron spectroscopy and atomic force microscopy. Subsequently, the antithrombotic properties of the coating were evaluated by measuring platelet count and thrombin-antithrombin complex levels of whole human blood after 3 h of incubation in a Chandler loop model. Scanning electron microscopy was utilized to examine thrombus formation on the stent surface. We observed that MPC polymer-coated stents significantly reduced thrombus formation as compared to bare stents and several clinically approved devices. Finally, the coated stents were further analyzed by implanting them in the internal thoracic arteries of pigs. Angiographic imaging and histopathological examinations that were performed one week after implantation revealed that the vascular lumen was well maintained and coated stents were integrated within the vascular endothelium without inducing adverse effects. Thus, we demonstrated the efficacy of MPC polymer coating as a viable strategy for avoiding the thrombotic risks associated with neurovascular stents.

Stent coating containing a charged silane coupling agent that regulates protein adsorption to confer antithrombotic and cell-adhesion properties.

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.

Finite element analysis of blood clots based on the nonlinear visco-hyperelastic model.

Mechanical thrombectomy has become the standard treatment for patients with an acute ischemic stroke. In this approach, to remove blood clots, mechanical force is applied using thrombectomy devices, in which the interaction between the clot and the device could significantly affect the clot retrieval performance. It is expected that the finite element method (FEM) could visualize the mechanical interaction by the visualization of the stress transmission from the device to the clot. This research was aimed at verifying the constitutive theory by implementing FEM based on the visco-hyperelastic theory, using a three-dimensional clot model. We used the visco-hyperelastic FEM to reproduce the mechanical behavior of blood clots, as observed in experiments. This study is focused on the mechanical responses of clots under tensile loading and unloading because in mechanical thrombectomy, elongation is assumed to occur locally on the clots during the retrieval process. Several types of cylindrical clots were created by changing the fibrinogen dose. Tensile testing revealed that the stiffness (E0.45-value) of clots with fibrinogen could be more than three times higher than that of clots without fibrinogen. It was also found that the stiffness was not proportional to the fibrinogen dose. By fitting to the theoretical curve, it was revealed that the Mooney-Rivlin model could reproduce the hyperelastic characteristics of clots well. From the stress-relaxation data, the three-chain Maxwell model could accurately fit the experimental viscoelastic data. FEM, taking the theoretical models into account, was then carried out, and the results matched well with the experimental visco-hyperelastic characteristics of clots under tensile load, reproducing the mechanical hysteresis during unloading, the stress dependence on the strain rate, and the time-dependent stress decrease in the stress-relaxation test.

Comparison of simulated structural deformation with experimental results after Wingspan stenting.

OBJECTIVES: Biomechanical stress distribution correlates with the biological responses after stenting. Computational analyses have contributed to the optimization of stent geometry. In particular, structural analysis based on pre-operative angiography can be used to predict the stent-artery interaction before endovascular treatments. However, the simulated results need to be validated. In this report, we compared the simulated arterial structure with post-operative images after an intracranial Wingspan stent. METHODS: A Wingspan stent was deployed at a slightly curved ascending pharyngeal artery (APA) in the swine. Using a finite element method (FEM), the configuration after stenting was simulated and quantitatively compared with post-procedural 3D angiography. RESULTS: The finite element analysis demonstrated arterial straightening after stenting. The simulated images were similar to the experimental results with respect to the curvature index of the center line and the cross-sectional areas. CONCLUSION: We assessed the simulated structural deformation after Wingspan stenting, by comparison with experimental results.

Structural analysis for Wingspan stent in a perforator model.

Perforator infarction represents a critical problem after intracranial Wingspan stent. To explore the mechanism of perforator infarction, we simulated the stent-artery interaction at an atheromatous plaque with perforator. Structural deformation and biomechanical stress distribution after stenting were analyzed. High radial stress values were located along the stent struts, which surrounded the area with high circumferential stress. Stretched perforator orifice in a circumferential direction after stenting was simulated. These results show that structural deformation could play a role in the mechanism of perforator occlusion after Wingspan stenting.

Simulated biomechanical responses at a curved arterial segment after Wingspan Stent deployment in swine.

OBJECTIVES: Endovascular treatment with the Wingspan Stent is frequently associated with in-stent restenosis at the curved portion, leading to late-phase stroke. To explore the cause of stroke complications after treatment with the Wingspan Stent, we simulated the biomechanical responses at a curved arterial segment using the finite element method. METHODS: A Wingspan stent was deployed at a slightly curved ascending pharyngeal artery (APA) in swine. Several stress distributions modeling solid mechanics were analyzed with structural deformation. Histopathological analysis of the selected APA was assessed at 28 days after stenting. RESULTS: Arterial straightening was simulated in this study. Both radial stress (RS) and circumferential stress (CS) concentrations increased at both stent ends. Marked lower axial stress (AS) concentration was observed at the outer wall of an arterial curvature. The proximal stent segment, ending in the curved portion, significantly impacted the solid mechanical environment. Eccentric neointimal hyperplasia was observed at the curved segment. DISCUSSION: These results show that the Wingspan stent exaggerated the non-uniform stress distributions in a curved artery. The understanding of stent-arterial wall interactions is of value to identify the current limitations of intracranial stenting, and will help to improve this treatment methodology and future devices.

Biomechanical responses after Wingspan Stent deployment in swine ascending pharyngeal artery.

OBJECTIVES: Symptomatic intracranial atherosclerotic stenosis is associated with a high rate of recurrent stroke. Endovascular angioplasty and stenting using the Wingspan(TM) Stent (Stryker) has been used for treatment of this disorder. However, a recent randomized trial (SAMMPRIS Clinical Trial) reported that it was inferior to aggressive medical management. To explore the cause of stroke complications after treatment with the Wingspan Stent, we simulated the biomechanical responses in a swine ascending pharyngeal artery (APA) using the finite element method. METHODS: A Wingspan Stent was deployed in a swine APA, and simulated stress distributions including radial, circumferential, and wall shear stress were evaluated. Histopathological analysis of the selected APA was made 28 days post-stenting. RESULTS: We detected increased radial stress concentration at distal stent markers with a stent edge and a graded augmentation of radial stress from proximal to distal. There was an impaired wall shear stress near the stent struts and stent markers. Intense neointimal hyperplasia was observed from the middle to distal segment of the stent 28 days after the procedure. DISCUSSION: This preliminary data suggest that the Wingspan Stent produces increased radial stress distribution with distal segment in a tapering artery. It is possible that the radial stress concentration plays a role in the development of neointimal hyperplasia.

Intra-aneurysmal hemodynamic alterations by a self-expandable intracranial stent and flow diversion stent: high intra-aneurysmal pressure remains regardless of flow velocity reduction.

OBJECT: Little is known about how much protection a flow diversion stent provides to a non-thrombosed aneurysm without the adjunctive use of coils. METHODS: A three-dimensional anatomically realistic computation aneurysm model was created from the digital subtraction angiogram of a large internal carotid artery-ophthalmic artery aneurysm which could have been treated with either a neck bridging stent or a flow diversion stent. Three-dimensional computational models of the Neuroform EZ neck bridging stent and Pipeline embolization device were created based on measurements with a stereo-microscope. Each stent was placed in the computational aneurysm model and intra-aneurysmal flow structures were compared before and after placement of the stents. Computational fluid dynamics were performed by numerically solving the continuity and Navier-Stokes momentum equations for a steady blood flow based on the finite volume method. Blood was assumed as an incompressible Newtonian fluid. Vessel walls were assumed to be rigid, and no-slip boundary conditions were applied at the lumens. To estimate the change in the intra-aneurysmal pressures we assumed that, at the inlets, the intra-arterial pressure at peak systole was 120 mm Hg both before and after stent placement RESULTS: Without any stent, the blood flow entered into the aneurysm dome from the mid to proximal neck area and ascended along the distal wall of the aneurysm. The flow then changed its direction anteriorly and moved along the proximal wall of the aneurysm dome. In addition to the primary intra-aneurysmal circulation pattern, a counterclockwise vortex was observed in the aneurysm dome. The placement of a Neuroform EZ stent induced a mean reduction in flow velocity of 14% and a small change in the overall intra-aneurysmal flow pattern. The placement of a Pipeline device induced a mean reduction in flow velocity of 74% and a significant change in flow pattern. Despite the flow velocity changes, Neuroform EZ and Pipeline devices induced reductions in intra-aneurysmal pressure of only 4 mm Hg and 8 mm Hg, respectively. CONCLUSIONS: The flow diversion effects of both stents were limited to flow velocity reduction. In a non-thrombosed aneurysm or an aneurysm with delayed thrombosis, the intra-aneurysmal pressure remains essentially unchanged regardless of the level of the intra-aneurysmal flow velocity reduction induced by the stents.

Mechanical design of an intracranial stent for treating cerebral aneurysms.

Endovascular treatment of cerebral aneurysms using stents has advanced markedly in recent years. Mechanically, a cerebrovascular stent must be very flexible longitudinally and have low radial stiffness. However, no study has examined the stress distribution and deformation of cerebrovascular stents using the finite element method (FEM) and experiments. Stents can have open- and closed-cell structures, and open-cell stents are used clinically in the cerebrovasculature because of their high flexibility. However, the open-cell structure confers a risk of in-stent stenosis due to protrusion of stent struts into the normal parent artery. Therefore, a flexible stent with a closed-cell structure is required. To design a clinically useful, highly flexible, closed-cell stent, one must examine the mechanical properties of the closed-cell structure. In this study, we investigated the relationship between mesh patterns and the mechanical properties of closed-cell stents. Several mesh patterns were designed and their characteristics were studied using numerical simulation. The results showed that the bending stiffness of a closed-cell stent depends on the geometric configuration of the stent cell. It decreases when the stent cell is stretched in the circumferential direction. Mechanical flexibility equal to an open-cell structure was obtained in a closed-cell structure by varying the geometric configuration of the stent cell.