Degree Of Endothelialization Research Articles

Early vascular healing after neXt-generation drug-eluting stent implantation in Patients with non-ST elevation acute Coronary syndrome: a randomized optical coherence Tomography imaging study (EXPECT).

Early vascular healing after drug-eluting stent (DES) implantation is associated with better outcomes and lower incidence of in-stent thrombosis. To examine vascular healing response in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) guided by optical coherence tomography (OCT) versus angiography alone. Sixty patients were randomized 1:1:1 to OCT-guided PCI with 3-month OCT follow-up (O3 group, n = 20), angiography-guided PCI with 3-month OCT follow-up (A3 group, n = 20), or angiography-guided PCI with 6-month OCT follow-up (A6 group, n = 20). The primary endpoint was the proportion of covered struts at 3- or 6-month follow-up. The proportion of covered struts in the O3 group was significantly higher than in the A3 group (95.2% vs. 92.3%, p < 0.001), but lower than in the A6 group (95.2% vs. 97.4%, p < 0.001). The O3 group had a lower proportion of incomplete strut apposition (ISA) than the A3 group (0.46% vs. 0.76%, p = 0.006), and higher than the A6 group (0.46% vs. 0.27%, p = 0.018) at follow-up. The optimal cut-off value of ISA after implantation of DES for predicting stent coverage at 3 and 6-month follow-up was 200μm and 308μm, respectively. Only one patient experienced target lesion revascularization in the A3 group during a 3-year clinical follow-up. In patients with NSTE-ACS undergoing PCI with DES, OCT guidance achieved higher strut coverage compared with angiography guidance at 3-month follow-up. However, the difference in the strut coverage between the OCT-guided group and the angiography-guided group at 6 months indicates that the degree of endothelialization may be more time-dependent instead of invasive device guidance.

Formation of Stable Vascular Networks by 3D Coaxial Printing and Schiff-Based Reaction.

Vascularized organs hold potential for various applications, such as organ transplantation, drug screening, and pathological model establishment. Nevertheless, the in vitro construction of such organs encounters many challenges, including the incorporation of intricate vascular networks, the regulation of blood vessel connectivity, and the degree of endothelialization within the inner cavities. Natural polymeric hydrogels, such as gelatin and alginate, have been widely used in three-dimensional (3D) bioprinting since 2005. However, a significant disparity exists between the mechanical properties of the hydrogel materials and those of human soft tissues, necessitating the enhancement of their mechanical properties through modifications or crosslinking. In this study, we aim to enhance the structural stability of gelatin-alginate hydrogels by crosslinking gelatin molecules with oxidized pullulan (i.e., a polysaccharide) and alginate molecules with calcium chloride (CaCl2). A continuous small-diameter vascular network with an average outer diameter of 1 mm and an endothelialized inner surface is constructed by printing the cell-laden hydrogels as bioinks using a coaxial 3D bioprinter. The findings demonstrate that the single oxidized pullulan crosslinked gelatin and oxidized pullulan/CaCl2 double-crosslinked gelatin-alginate hydrogels both exhibit a superior structural stability compared to their origins and CaCl2 solely crosslinked gelatin-alginate hydrogels. Moreover, the innovative gelatin and gelatin-alginate hydrogels, which have excellent biocompatibilities and very low prices compared with other hydrogels, can be used directly for tissue/organ construction, tissue/organ repairment, and cell/drug transportation.

Construction of a small-caliber tissue-engineered blood vessel using icariin-loaded β-cyclodextrin sulfate for in situ anticoagulation and endothelialization.

The rapid endothelialization of tissue-engineered blood vessels (TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for the treatment of cardiovascular diseases. β-cyclodextrin sulfate is a type of hollow molecule that has good biocompatibility and anticoagulation properties and exhibits a sustained release of icariin. We studied whether icariin-loaded β-cyclodextrin sulfate can promote the endothelialization of TEBVs. The experimental results showed that icariin could significantly promote the proliferation and migration of endothelial progenitor cells; at the same time, icariin could promote the migration of rat vascular endothelial cells (RAVECs). Subsequently, we used an electrostatic force to modify the surface of the TEBVs with icariin-loaded β-cyclodextrin sulfate, and these vessels were implanted into the rat common carotid artery. After 3 months, micro-CT results showed that the TEBVs modified using icariin-loaded β-cyclodextrin sulfate had a greater patency rate. Scanning electron microscopy (SEM) and CD31 immunofluorescence results showed a better degree of endothelialization. Taken together, icariin-loaded β-cyclodextrin sulfate can achieve anticoagulation and rapid endothelialization of TEBVs to ensure their long-term patency.

Assessment of endothelialization of aneurysm wall over time in a rabbit model through CD31 scoring

BackgroundIntracranial aneurysms represent a significant health concern and are poorly understood despite decades of research. Our study focused on understanding temporal patterns of endothelial cell distribution in different spatial locations...

TCT-793 Metformin Impairs Endothelialization After Placement of Newer Generation Drug Eluting Stents

Objectives: Metformin impairs endothelialization of drug eluting stents (DES) due to convergent signaling at the mammalian target of rapamycin (mTOR) pathway. We assessed whether metformin will continue to adversely affect stent endothelialization despite design improvements in newer generation DES. Methods: Rabbit iliac artery stenting with newer generation DES was performed followed by 14 days of either normal chow diet or one with metformin (100 mg/kg/day) added. Scanning electron microscopy was used to assess stent endothelialization after sacrifice. Results: In the metformin-treated group there was significantly less endothelialization compared to the placebo-treated group. Paclitaxel-eluting stents in placebo-treated group had the greatest degree of endothelialization with significantly less in its metformin-treated counterpart and allelimus eluting stent groups. Conclusions: Metformin inhibited stent endothelialization in newer generation DES despite improvements in stent design. By impairing stent endothelialization, metformin may increase the risk for thrombotic complications after newer generation DES placement.

Letter by Pérez de Prado et al Regarding Article, “Delayed Coverage in Malapposed and Side-Branch Struts With Respect to Well-Apposed Struts in Drug-Eluting Stents: In Vivo Assessment With Optical Coherence Tomography”

HomeCirculationVol. 125, No. 10Letter by Pérez de Prado et al Regarding Article, “Delayed Coverage in Malapposed and Side-Branch Struts With Respect to Well-Apposed Struts in Drug-Eluting Stents: In Vivo Assessment With Optical Coherence Tomography” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Pérez de Prado et al Regarding Article, “Delayed Coverage in Malapposed and Side-Branch Struts With Respect to Well-Apposed Struts in Drug-Eluting Stents: In Vivo Assessment With Optical Coherence Tomography” Armando Pérez de Prado, MD, Carlos Cuellas-Ramón, MD and Felipe Fernández-Vázquez, MD, PhD Armando Pérez de PradoArmando Pérez de Prado Search for more papers by this author , Carlos Cuellas-RamónCarlos Cuellas-Ramón Search for more papers by this author and Felipe Fernández-VázquezFelipe Fernández-Vázquez Search for more papers by this author Originally published13 Mar 2012https://doi.org/10.1161/CIRCULATIONAHA.111.064493Circulation. 2012;125:e458To the Editor:We read with great interest the article by Gutiérrez-Chico et al,1 which reports delayed coverage of incompletely apposed and nonapposed side-branch struts with respect to well-apposed struts in drug-eluting stents as assessed by optical coherence tomography. The relationship between incomplete stent apposition and delayed strut coverage has previously been explored. However, the study of fate of nonapposed side-branch struts is quite original.These struts, placed across the origin of side branches, have systematically been excluded from analysis in most of the published optical coherence tomography studies. Intuitively, they were deemed not suitable to be covered. These new results abrogate that theory, demonstrating by optical coherence tomography analysis that up to 78.1% of these struts appear covered 9 to 13 months after drug-eluting stent implantation. This finding is indeed relevant, but a question arises: What is covering those struts? As the authors acknowledge, optical coherence tomography covering is not a surrogate for neointimal healing. The vascular healing process involves the participation of the coagulation system and many types of cells in different phases, all of them covering the stent struts. Optical coherence tomography is unable to distinguish between fibrin, giant cells, granulomatous reaction, and degree of endothelialization.2 Until we can confirm recent findings with optical density analysis that claims being able to distinguish between neointima and fibrin/thrombus,3 we can only search for clues. Can the authors offer any extra information that helps in this endeavor? Is there any difference in the thickness of the coverage between apposed and nonapposed struts?We have previously reported that these nonapposed side-branch struts show a high reendothelialization rate in a swine coronary model.4 Our data coincide with the results presented by Gutiérrez-Chico et al1: Nonapposed side-branch struts show delayed endothelialization but a parallel time course to the rest of struts. The endothelial cells that cover these nonapposed struts necessarily come from circulating endothelial progenitor cells because there is no chance of repopulation from the surrounding area. The animal models use young, healthy individuals as opposed to human patients with defective healing mechanisms. Whether these findings predict a similar behavior in the clinical setting is still unknown.It is common to observe nonapposed struts placed over the side-branch origin; up to 41% of the analyzed stents were nonapposed.1 In daily practice, the rate should be even higher because the analysis refers to randomized studies with moderate stent lengths. Therefore, the clinical relevance of the status of these struts is not negligible. Whatever the coverage of these struts is, some issues must be considered. One of them emerges from the use of the new bioresorbable scaffolds. The struts of these prostheses, also those located over the side-branch takeoff, finally disappear as expected.5 Do they show a strut coverage similar to that observed in metallic stents? Can the breakdown of the scaffold cause clinically relevant side-branch embolism? We guess this topic will prompt further analyses of these floating struts in different situations.Armando Pérez de Prado, MDCarlos Cuellas-Ramón, MDFelipe Fernández-Vázquez, MD, PhD Fundación Investigación Sanitaria en León–HemoLeon Instituto de Biomedicina (IBIOMED) Hospital de León–Universidad de León León, SpainDisclosuresNone.

Development of a Novel Prohealing Stent Designed to Deliver Sirolimus From a Biodegradable Abluminal Matrix

We aimed to demonstrate that, by separating endothelial progenitor cell capture from sirolimus delivery through the application of drug to the abluminal surface of the stent, the degree of endothelialization can be enhanced. Stainless steel R Stents, with biodegradable SynBiosys polymer coating with sirolimus abluminally applied and surface modified with anti-CD34 antibody were prepared at 2 dosages (low-dose sirolimus [LD-Combo, 2.5 microg sirolimus/mm] and full-dose sirolimus [Combo, 5 microg sirolimus/mm). These Combo stents and the Cypher stent (10 microg sirolimus/mm) were deployed in 98 normal porcine arteries and harvested for pharmacokinetic analysis at 0.25, 1, 3, 7, 14, 28, and 35 days. The LD-Combo stents showed faster early release (50%total dose in 72 hours) than the Combo and Cypher. At 30 days, drug release was near complete with both Combo stents, whereas 20% of drug remained on the Cypher stents. To assess efficacy, a total of 50 stents (Xience V=8, Cypher=8, Genous bioengineered R stent=6, LD-Combo=14, and Combo=14) were implanted in 18 pigs for 14 and 28 days. Optical coherence tomography was performed, and stents were harvested for histology. At 28 days, there was less neointimal thickness with Combo (0.173+/-0.088 mm) compared with Cypher (0.358+/-0.225 mm), LD-Combo (0.316+/-0.228 mm), and Xience V (0.305+/-0.252 mm; P<0.00001). Immunohistochemical analysis of endothelialization showed that Genous bioengineered R stent had the highest degree of platelet endothelial cell adhesion molecule expression (87%) followed by the Combo (75%), LD-Combo (65%), and Cypher (58%). Both optical coherence tomography and histology demonstrate that anti-CD34 sirolimus-eluting stents promote endothelialization while reducing neointimal formation and inflammation.

The pro-angiogenic factor CCN1 enhances the re-endothelialization of biological vascularized matrices in vitro

A problem in generating artificial tissues is supplying nutrients to cells within 3D constructs. The use of a decellularized biological vascularized matrix with preserved pedicles (BioVaM), as a scaffold, appears to aid the generation of perfusable tissue constructs in vitro. To prevent vessel occlusion upon implantation, a functional endothelium must line the graft vessel bed. Here we tested whether the pro-angiogenic factor CCN1 could improve the re-endothelialization of BioVaM in vitro. BioVaM vessel beds were incubated with 100 ng/mL recombinant human CCN1. Human cord blood endothelial cells (hCBEC) were analysed with respect to adhesion behaviour upon CCN1 exposure and seeded onto vessel structures of CCN1 exposed BioVaM (cBioVaM). BioVaMs were fixed in a bioreactor and perfusion cultured for 4 and 14 days (d). BioVaM without CCN1 treatment served as controls. Initial seeding success and endothelialization progression were monitored by fluorescence-labelled hCBEC. During construct cultivation, pH and lactate production were measured. Degree of endothelialization and characterization of seeded cells, with respect to endothelial markers, were investigated histologically. BioVaM vessel structures showed a 78 +/- 17% increase of attached cells when pre-treated with CCN1. Evaluation of re-endothelialization (arbitrary units) was 4.0 +/- 0.8 and 2.6 +/- 0.8 after 4 d, and 5.0 +/- 0.0 and 3.0 +/- 0.5 after 14 d in cBioVaM vs. BioVaM, respectively. On day 14, lactate concentration, an indicator of metabolic activity, was increased 12-fold in cBioVaM relative to BioVaM. A preserved endothelial phenotype of seeded cells was verified in all cultures by acetylated low density lipoprotein uptake and positive immunohistochemistry against von Willebrand factor, endothelial nitric oxide synthase, and CD31. Coating of decellularized vessel structures with CCN1 supports adhesion of hCBEC and enhances re-endothelialization of BioVaM. Perfusable, endothelialized constructs may aid in solving the problem of nourishing cells inside 3D tissue-engineered constructs.

Covered stents in transjugular portosystemic shunt: healing response to non-porous ePTFE covered stent grafts with and without intraluminal irradiation.

The aim of this study was to evaluate the healing response to a new commercially available ePTFE-covered stent graft used to create transjugular intrahepatic portosystemic shunts (TIPS) in an animal model with and without intraluminal irradiation. The study was designed for ten domestic normotensive pigs. The TIPS was created using a ePTFE-covered stent graft (Viatorr, Gore, Flagstaff, Ariz.). Five animals were scheduled for intraluminal irradiation with iridium 192 immediately after TIPS creation with a dosage of 18 Gy. Shunt venograms were performed every 2 weeks. Animals from the irradiated and non-irradiated group were killed at 2-week intervals. Maximum follow-up was planned for 8 weeks in each group, with two animals in reserve. Gross specimen evaluation and histological examination, including scanning electron microscopy, was performed. Two animals died from interventional complications. In the irradiation group, one shunt occlusion and one stenosis occurred after 2 weeks. The stenosis regressed until the end of the 8-week follow-up period and probably was caused by a resolving thrombus. In the non-irradiated group, no shunt dysfunction was observed. One animal died early due to encephalopathy. Histology revealed an increased inflammatory reaction in the irradiation group, a lesser degree of incorporation of the stent graft, and a lesser degree of endothelialization of the inner surface compared with the non-irradiated group. No significant foreign body reaction was found at any time in any of the animals. The Viatorr stent graft was well tolerated in the pig model. Intraluminal irradiation seemed to have an adverse effect on the healing response. The TIPS patency was prolonged in both the irradiated and non-irradiated group compared with data from the literature; however, seemingly better results were observed in the non-irradiated group.