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Coronary artery stenting following balloon angioplasty represents the gold standard in revascularization of coronary artery stenoses. However, stent deployment as well as percutaneous transluminal coronary angioplasty (PTCA) alone causes severe injury of vascular endothelium. The damaged endothelium is intrinsically repaired by locally derived endothelial cells and by circulating endothelial progenitor cells from the blood, leading to re‐population of the denuded regions within several weeks to months. However, the process of re‐endothelialization is often incomplete or dysfunctional, promoting in‐stent thrombosis and restenosis. The molecular and biomechanical mechanisms that influence the process of re‐endothelialization in stented segments are incompletely understood. Once the endothelium is restored, endothelial function might still be impaired. Several strategies have been followed to improve endothelial function after coronary stenting. In this review, the effects of stenting on coronary endothelium are outlined and current and future strategies to improve endothelial function after stent deployment are discussed.

Abstract Flow diverters have drastically changed the landscape of intracranial aneurysm treatment and are now considered first-line therapy for select lesions. Their mechanism of action relies on intrinsic alteration in hemodynamic parameters, both at the parent artery and within the aneurysm sac. Moreover, the device struts act as a nidus for endothelial cell growth across the aneurysm neck ultimately leading to aneurysm exclusion from the circulation. In silico computational analyses and investigations in preclinical animal models have provided valuable insights into the underlying biological basis for flow diverter therapy. Here, we review the present understanding pertaining to flow diverter biology and mechanisms of action, focusing on stent design, induction of intra-aneurysmal thrombosis, endothelialization, and alterations in hemodynamics.

IMP3, an RNA‐binding protein (RBP) that participates in the process of post‐transcriptional modifications of mRNA transcripts, is capable of altering cellular functions, and in some cases, be involved in specific disease progression. We aimed to investigate whether IMP3 has the ability to regulate the functional properties of endothelial cells and re‐endothelialization in response to arterial injury. Wire injury was introduced to the right carotid arteries of wildtype C57/BL6 mice. As a result, IMPs’ expressions were up‐regulated in the induced arterial lesions, and IMP3 was the most up‐regulated RNA among other IMPs. We overexpressed IMP3 before the wire‐injured surgery using adeno‐associated virus AAV2‐IMP3. In vivo studies confirmed that IMP3 overexpression accelerated the progress of re‐endothelialization after arterial injury. In vitro, endothelial cells were transfected with either ad‐IMP3 or Si‐IMP3, cell functional studies showed that IMP3 could promote endothelial cell proliferation and migration, while reducing apoptosis. Mechanistic studies also revealed that IMP3 could enhance VEGF mRNA stability and therefore up‐regulate activities of VEGF/PI3K/Akt signalling pathway. Our data indicated that IMP3 promotes re‐endothelialization after arterial injury and regulates endothelial cell proliferation, migration and apoptosis via increasing stability of VEGF mRNA and activation of VEGF/PI3K/Akt signalling pathway.

Endothelial injury is a common occurrence following stent implantation, often leading to complications such as restenosis and thrombosis. To address this issue, we have developed a multi‐functional stent coating that combines a dopamine‐copper (DA‐Cu) base with therapeutic biomolecule modification, including nitric oxide (NO) precursor L‐arginine, endothelial glycocalyx heparin, and endothelial cell (EC) catcher vascular endothelial growth factor (VEGF). In our stent coating, the incorporated Cu acts as a sustainable catalyst for converting endogenous NO donors into NO, and the immobilized arginine serves as a precursor for NO generation under the effect of endothelial nitric oxide synthase (eNOS). The presence of heparin endows the stent coating with anticoagulant ability and enhances eNOS activity, whilst rapid capture of EC by VEGF accelerates re‐endothelialization. After in vivo implantation, the antioxidant elements and produced NO alleviate the inflammatory response, establishing a favorable healing environment. The conjugated VEGF contributes to the formation of a new and intact endothelium on the stent surface to counteract inappropriate vascular cell behaviors. The long‐lasting NO flux inhibits smooth muscle cell (SMC) migration and prevents its excessive proliferation, reducing the risk of endothelial hyperplasia. This innovative coating enables the dual delivery of VEGF and NO to target procedural vascular repair phases: promoting rapid re‐endothelialization, effectively preventing thrombosis, and suppressing inflammation and restenosis. Ultimately, this innovative coating has the potential to improve therapeutic outcomes following stent implantation. This project develops a biomimetic stent coating with a double presentation of therapeutic biomacromolecule VEGF and therapeutic gas NO, which spatiotemporally promotes vessel repair including promoting rapid re‐endothelialization, effectively preventing thrombosis, suppressing inflammation and restenosis.

Nitric oxide (NO) and hydrogen sulfide (H2S) gasotransmitters exhibit potential therapeutic effects in the cardiovascular system. Herein, biomimicking multilayer structures of biological blood vessels, bilayer small-diameter vascular grafts (SDVGs) with on-demand NO and H2S release capabilities, were designed and fabricated. The keratin-based H2S donor (KTC) with good biocompatibility and high stability was first synthesized and then electrospun with poly (l-lactide-co-caprolactone) (PLCL) to be used as the outer layer of grafts. The electrospun poly (ε-caprolactone) (PCL) mats were aminolyzed and further chelated with copper (II) ions to construct glutathione peroxidase (GPx)-like structural surfaces for the catalytic generation of NO, which acted as the inner layer of grafts. The on-demand release of NO and H2S selectively and synergistically promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) while inhibiting the proliferation and migration of human umbilical artery smooth muscle cells (HUASMCs). Dual releases of NO and H2S gasotransmitters could enhance their respective production, resulting in enhanced promotion of HUVECs and inhibition of HUASMCs owing to their combined actions. In addition, the bilayer grafts were conducive to forming endothelial cell layers under flow shear stress. In rat abdominal aorta replacement models, the grafts remained patency for 6 months. These grafts were capable of facilitating rapid endothelialization and alleviating neointimal hyperplasia without obvious injury, inflammation, or thrombosis. More importantly, the grafts were expected to avoid calcification with the degradation of the grafts. Taken together, these bilayer grafts will be greatly promising candidates for SDVGs with rapid endothelialization and anti-calcification properties. [Display omitted] •Mimicking multilayer structures of a blood vessel, bilayer vascular grafts with respective NO and H2S release capabilities were designed and fabricated for the first time. The novel H2S donor of KTC was synthesized and then electrospun with PLCL to be used as the outer layer. The glutathione peroxidase (GPx)-like inner layer was formed for the catalytic generation of NO. The on-demand released NO and H2S selectively and synergistically regulate vascular endothelial cells and smooth muscle cells. In a rat abdominal aorta replacement model, the grafts remained patency without calcification for 6 months. More importantly, these grafts were capable to facilitate rapid endothelialization and alleviate neointimal hyperplasia without obvious injury, inflammation, and thrombosis.

Cerebral aneurysm (CA) is a significant health concern that results from pathological dilations of blood vessels in the brain and can lead to severe and potentially life-threatening conditions. While the pathogenesis of CA is complex, emerging studies suggest that endothelial progenitor cells (EPCs) play a crucial role. In this paper, we conducted a comprehensive literature review to investigate the potential role of EPCs in the pathogenesis and treatment of CA. Current research indicates that a decreased count and dysfunction of EPCs disrupt the balance between endothelial dysfunction and repair, thus increasing the risk of CA formation. Reversing these EPCs abnormalities may reduce the progression of vascular degeneration after aneurysm induction, indicating EPCs as a promising target for developing new therapeutic strategies to facilitate CA repair. This has motivated researchers to develop novel treatment options, including drug applications, endovascular-combined and tissue engineering therapies. Although preclinical studies have shown promising results, there is still a considerable way to go before clinical translation and eventual benefits for patients. Nonetheless, these findings offer hope for improving the treatment and management of this condition.

To successfully engineer large-sized tissues, establishing vascular structures is essential for providing oxygen, nutrients, growth factors and cells to prevent necrosis at the core of the tissue. The diameter scale of the biofabricated vasculatures should range from 100 to 1,000 µm to support the mm-size tissue while being controllably aligned and spaced within the diffusion limit of oxygen. In this review, insights regarding biofabrication considerations and techniques for engineered blood vessels will be presented. Initially, polymers of natural and synthetic origins can be selected, modified, and combined with each other to support maturation of vascular tissue while also being biocompatible. After they are shaped into scaffold structures by different fabrication techniques, surface properties such as physical topography, stiffness, and surface chemistry play a major role in the endothelialization process after transplantation. Furthermore, biological cues such as growth factors (GFs) and endothelial cells (ECs) can be incorporated into the fabricated structures. As variously reported, fabrication techniques, especially 3D printing by extrusion and 3D printing by photopolymerization, allow the construction of vessels at a high resolution with diameters in the desired range. Strategies to fabricate of stable tubular structures with defined channels will also be discussed. This paper provides an overview of the many advances in blood vessel engineering and combinations of different fabrication techniques up to the present time.

Bioengineered livers are currently an acceptable alternative to orthotopic liver transplants to overcome the scarcity of donors. However, the challenge of using a bioengineered liver is the lack of an intact endothelial layer in the vascular network leading to thrombosis. Heparin-modified surfaces have been demonstrated to decrease thrombogenicity in earlier research. However, in our study, we aimed to apply heparin immobilization to enhance the hemocompatibility, endothelial cell (EC) adhesion, and angiogenesis of rat decellularized liver scaffolds (DLS). Heparin was immobilized on the DLS by the end-point attachment technique. The scaffold’s hemocompatibility was assessed using ex vivo blood perfusion and platelet adhesion studies. The heparinized scaffold (HEP-DLS) showed a significantly reduced thrombogenicity and platelet aggregation. HEP-DLS was recellularized with EA.hy926 cells via the portal vein and maintained in the bioreactor for 7 days, showing increased EC adhesion and coverage within the blood vessels. The Resazurin reduction assay confirmed the presence of actively proliferating cells in the HEP-DLS. The scaffolds were implanted subcutaneously into the dorsum of mice for 21 days to evaluate cell migration and angiogenesis. The results showed significant increases in the number of blood vessels in the HEP-DLS group. Our results demonstrated that heparin immobilization reduces thrombosis, promotes re-endothelialization, and enhances angiogenesis in DLS. The research provides insight into the potential use of heparin in the formation of a functioning vasculature.

Polyurethane (PU) is widely used in medical products due to its biocompatibility and mechanical properties. Electrospinning (ES) was employed to produce PU-based scaffolds intended for cardiovascular devices (CVD) from blends of Carbothane (Carb) with human serum albumin (HSA), dimethylacetamide (DMA), and drugs. Sirolimus (SRL)-an immunosuppressive/anti-proliferative drug-and diclofenac (DF)-a nonsteroidal anti-inflammatory drug-were introduced into ES blends to produce drug-enriched scaffolds that prevent inflammation and cell overgrowth. The biocompatibility, stability, and mechanical properties of the scaffolds and SRL release were studied. The scaffolds possessed good mechanical properties and were stable in PBS and blood plasma (BP) for 120 days. The minimal SRL release rate was observed for the scaffold 3%Carb/10%HSA/DMA/SRL. A study of scaffold interaction with blood demonstrated good hemocompatibility of most scaffolds. A study of human gingival fibroblasts, endothelial cells (HUVEC and EA.hy926), and vascular smooth muscle cell interaction with scaffolds in vitro demonstrated variability in cell viability and pro-inflammatory interleukin IL-6 secretion, depending on both the scaffold composition and the cell type. The incorporation of DF into scaffolds decreased the concentration of IL-6 in the culture medium. The scaffold 3%Carb/10%HSA/DMA/SRL is the best choice for CVD in terms of hemocompatibility, endothelialization, and the induction of minimal inflammation.

Magnesium alloy stents have been extensively studied in the field of biodegradable metal stents due to their exceptional biocompatibility, biodegradability and excellent biomechanical properties. Nevertheless, the specific in vivo service environment causes magnesium alloy stents to degrade rapidly and fail to provide sufficient support for a certain time. Compared to previous reviews, this paper focuses on presenting an overview of the development history, the key issues, mechanistic analysis, traditional protection strategies and new directions and protection strategies for magnesium alloy stents. Alloying, optimizing stent design and preparing coatings have improved the corrosion resistance of magnesium alloy stents. Based on the corrosion mechanism of magnesium alloy stents, as well as their deformation during use and environmental characteristics, we present some novel strategies aimed at reducing the degradation rate of magnesium alloys and enhancing the comprehensive performance of magnesium alloy stents. These strategies include adapting coatings for the deformation of the stents, preparing rapid endothelialization coatings to enhance the service environment of the stents, and constructing coatings with self-healing functions. It is hoped that this review can help readers understand the development of magnesium alloy cardiovascular stents and solve the problems related to magnesium alloy stents in clinical applications at the early implantation stage.