Cardiovascular stent restenosis remains a major challenge in interventional treatment of cardiovascular occlusive disease. Although the changes in arterial mechanical environment due to stent implantation are the main causes of the initiation of restenosis and thrombosis, the mechanisms that cause this initiation are still not fully understood. In this article, we reviewed the studies on the issue of stent-induced alterations in arterial mechanical environment and discussed their roles in stent restenosis and late thrombosis from three aspects: (i) the interaction of the stent with host blood vessel, involve the response of vascular wall, the mechanism of mechanical signal transmission, the process of re-endothelialization and late thrombosis; (ii) the changes of hemodynamics in the lumen of the vascular segment and (iii) the changes of mechanical microenvironment within the vascular segment wall due to stent implantation. This review has summarized and analyzed current work in order to better solve the two main problems after stent implantation, namely in stent restenosis and late thrombosis, meanwhile propose the deficiencies of current work for future reference.
Docetaxel (DTX), a paclitaxel analogue, can efficiently inhibit proliferation of vascular smooth muscle cells and has broadly been used as an antiangiogenesis drug. However, as a candidate drug of drug-eluting stent, the effects of DTX on human umbilical vein endothelial cells (HUVECs) are still not well understood. Herein, we investigated the effects of DTX on proliferation, apoptosis, adhesion, migration and morphology of HUVECs in vitro. We found that DTX had the cytostatic and cytotoxic effects at low and high concentrations, respectively. DTX could inhibit the proliferation and migration of HUVECs, induce HUVECs apoptosis, delay HUVECs adhesion and decrease spreading area and aspect ratio of individual cells. The signaling pathway that DTX led to the migration inhibition, adhesion delay and shape change of HUVECs is the VE-cadherin mediated integrin β1/FAK/ROCK signaling pathway. The study will provide a theoretical basis for the clinical application of DTX.
In clinical practice, the need for small‐diameter vascular grafts continues to increase. Decellularized xenografts are commonly used for vascular reconstructive procedures. Here, porcine coronary arteries are decellularized, which destroys the extracellular matrix structure, leading to the decrease of vascular strength and the increase of vascular permeability. A bilayer tissue‐engineered vascular graft (BTEV) is fabricated by electrospinning poly(l‐lactide‐co‐carprolactone)/gelatin outside of the decellularized vessels and functionalized by immobilizing heparin, which increases the biomechanical strength and anticoagulant activity of decellularized vessels. The biosafety and efficacy of the heparin‐modified BTEVs (HBTEVs) are verified by implanting in rat models. HBTEVs remain patent and display no expansion or aneurism. After 4 weeks of implantation, a cell monolayer in the internal surface and a dense middle layer have formed, and the mechanical properties of regenerated vessels are similar to those of rat abdominal aorta. Therefore, HBTEVs can be used for rapid remodeling of small‐diameter blood vessels.
Zinc (Zn) and its alloys have been proved to be promising candidate materials for biodegradable cardiovascular stents. In this study, a novel extruded Zn-0.02 Mg-0.02Cu alloy was prepared. Compared with pure Zn, the Zn-based alloy showed higher mechanical properties, and the Zn-based alloy could significantly accelerate Zn 2+ release, reaching 0.61 AE 0.11 μg/mL at 15 days of immersion. In vitro biocompatibility studies demonstrated that the Zn-based alloy had excellent cytocompatibility and hemocompatibility, including low hemolysis rate (0.63 AE 0.12%) and strong inhibitory effect on platelet adhesion. Subsequently, the Zn-based alloy stent was implanted into the left carotid arteries of New Zealand white rabbits for 12 months. All the rabbits survived without any adverse clinical events, and all the stented arteries were patent during the study period. Rapid endothelialization at 1 week of implantation was observed, suggesting a low cytotoxicity and thrombosis risk. The stent corroded slowly and no obvious intimal hyperplasia was observed for 6 months, after which corrosion accelerated at 12 months. In addition, no obvious thrombosis and systemic toxicity during implantation period were observed, indicating its potential as the backbone of biodegradable cardiovascular stents.
Atomic force microscopy probes are proved to be powerful tools to measure and manipulate the individual cell, providing potential applications for the controlled drug/protein delivery. However, the measured insertion efficiency varies dramatically from 20 to 80%, in some cases, the nanotip can never penetrate the cell membrane no matter how much force is applied to it. Thus, the insertion mechanism of a living cell during the tip-cell interaction must be thoroughly investigated before this technology comes into practical applications. In this work, a multistructural cell model is established to study the tip-membrane interaction. The simulation results show that the stress of the cell membrane can be divided into two stages by the stress segmentation point S. After point S, the stress of the cell membrane increases slightly and most of the indentation force is allocated to the cytoskeleton. This phenomenon is called "stress segmentation effect of the cell membrane," which confirms the hypothesis based on the experimental studies. Moreover, according to the experimental and numerical studies, the hypothesis of the stress segmentation effect also explains the reason that modifying the cell membrane or using the manmade sharpened nanotip can increase the insertion efficiency.
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