Preparation of Small‐Diameter Tissue‐Engineered Vascular Grafts Electrospun from Heparin End‐Capped PCL and Evaluation in a Rabbit Carotid Artery Replacement Model

2019 ◽  
Vol 19 (8) ◽  
pp. 1900114 ◽  
Author(s):  
Xin Jin ◽  
Xue Geng ◽  
Liujun Jia ◽  
Zeqin Xu ◽  
Lin Ye ◽  
...  
2019 ◽  
Vol 8 (2) ◽  
pp. 87-97
Author(s):  
L. V. Antonova ◽  
E. O. Krivkina ◽  
M. A. Rezvova ◽  
V. V. Sevost'yanova ◽  
A. V. Mironov ◽  
...  

Background. Tissue-engineered vascular grafts can be reinforced by a biostable or biodegradable polymer sheath. A combination of electrospinning, routinely used for fabrication of biodegradable tubular grafts, and the layer-by-layer coating allows forming a polymeric sheath ensuring long-term integrity and high biocompatibility of the vascular grafts after the implantation. Aim To evaluate mechanical properties and in vivo performance of biodegradable small-diameter vascular grafts with a reinforcing sheath.Methods. Tubular grafts (4 mm diameter) were fabricated from poly(3-hydroxybutyrate-co3-hydroxyvalerate) and poly(ε-caprolactone) by emulsion electrospinning with the incorporation of vascular endothelial growth factor (VEGF) into the inner third of the graft and basic fibroblast growth factor (bFGF) along with stromal cell-derived factor-1α (SDF-1α) into the outer two thirds of the graft wall. Poly(ε-caprolactone) sheath was formed by the layer-by-layer coating. Upon graft fabrication, scanning electron microscopy was performed to assess the grafts’ surface, tensile testing allowed evaluating mechanical properties. The samples were implanted into the ovine carotid artery (n = 5 animals) for 12 months with the subsequent histological examination.Results. Sintering temperature of 160°C during the extrusion allowed effective and delicate merging of poly(ε-caprolactone) coating with the outer surface of the poly(3hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) tubular graft. The thickness of poly(ε-caprolactone) fiber was 380–400 μm, the increment of the reinforcing filament was 1 mm. The reinforcing sheath led to a 3-fold increase in durability and elastic modulus of the vascular grafts. At the 12-months follow-up, the grafts reported retained integrity. No signs of inflammation or calcification were found.Conclusion. The poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(ε-caprolactone) vascular grafts with hierarchically incorporated growth factors and the reinforced poly(ε-caprolactone) spiral sheath demonstrated improved mechanical properties while retaining integrity and high biocompatibility after the long-term implantation into the ovine carotid artery.


2018 ◽  
Vol 13 (6) ◽  
pp. 065009 ◽  
Author(s):  
Jana Horakova ◽  
Petr Mikes ◽  
David Lukas ◽  
Ales Saman ◽  
Vera Jencova ◽  
...  

2020 ◽  
Vol 13 (5) ◽  
pp. 101
Author(s):  
Larisa V. Antonova ◽  
Andrey V. Mironov ◽  
Arseniy E. Yuzhalin ◽  
Evgeniya O. Krivkina ◽  
Amin R. Shabaev ◽  
...  

The development of novel biodegradable vascular grafts of a small diameter (<6 mm) is an unmet clinical need for patients requiring arterial replacement. Here we performed a pre-clinical study of new small-caliber biodegradable vascular grafts using a sheep model of carotid artery implantation. The 4 mm diameter vascular grafts were manufactured using a mix of polyhydroxybutyrate/valerate and polycaprolactone supplemented with growth factors VEGF, bFGF and SDF-1α (PHBV/PCL-GFmix) and additionally modified by a polymer hydrogel coating with incorporation of drugs heparin and iloprost (PHBV/PCL-GFmixHep/Ilo). Animals with carotid artery autograft implantation and those implanted with clinically used GORE-TEX® grafts were used as control groups. We observed that 24 h following surgery, animals with carotid artery autograft implantation showed 87.5% patency, while all the PHBV/PCL-GFmix and GORE-TEX® grafts displayed thrombosis. PHBV/PCL-GFmixHep/Ilo grafts demonstrated 62.5% patency 24 h following surgery and it had remained at 50% 1 year post-operation. All the PHBV/PCL grafts completely degraded less than 1 year following surgery and were replaced by de novo vasculature without evidence of calcification. On the other hand, GORE-TEX® grafts displayed substantial amounts of calcium deposits throughout graft tissues. Thus, here we report a potential clinical usefulness of PHBV/PCL grafts upon their additional modification by growth factors and drugs to promote endothelialization and reduce thrombogenicity.


Biomaterials ◽  
2012 ◽  
Vol 33 (10) ◽  
pp. 2880-2891 ◽  
Author(s):  
Wenting Zheng ◽  
Zhihong Wang ◽  
Lijie Song ◽  
Qiang Zhao ◽  
Jun Zhang ◽  
...  

1992 ◽  
Vol 12 (10) ◽  
pp. 1206-1213 ◽  
Author(s):  
S Kaul ◽  
R C Padgett ◽  
B J Waack ◽  
R M Brooks ◽  
D D Heistad

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1952
Author(s):  
Max Wacker ◽  
Jan Riedel ◽  
Heike Walles ◽  
Maximilian Scherner ◽  
George Awad ◽  
...  

In this study, we contrast the impacts of surface coating bacterial nanocellulose small-diameter vascular grafts (BNC-SDVGs) with human albumin, fibronectin, or heparin–chitosan upon endothelialization with human saphenous vein endothelial cells (VEC) or endothelial progenitor cells (EPC) in vitro. In one scenario, coated grafts were cut into 2D circular patches for static colonization of a defined inner surface area; in another scenario, they were mounted on a customized bioreactor and subsequently perfused for cell seeding. We evaluated the colonization by emerging metabolic activity and the preservation of endothelial functionality by water soluble tetrazolium salts (WST-1), acetylated low-density lipoprotein (AcLDL) uptake assays, and immune fluorescence staining. Uncoated BNC scaffolds served as controls. The fibronectin coating significantly promoted adhesion and growth of VECs and EPCs, while albumin only promoted adhesion of VECs, but here, the cells were functionally impaired as indicated by missing AcLDL uptake. The heparin–chitosan coating led to significantly improved adhesion of EPCs, but not VECs. In summary, both fibronectin and heparin–chitosan coatings could beneficially impact the endothelialization of BNC-SDVGs and might therefore represent promising approaches to help improve the longevity and reduce the thrombogenicity of BNC-SDVGs in the future.


1995 ◽  
Vol 269 (3) ◽  
pp. H805-H811 ◽  
Author(s):  
S. Najibi ◽  
R. A. Cohen

Endothelium-dependent relaxations to acetylcholine remain normal in the carotid artery of hypercholesterolemic rabbits, but unlike endothelium-dependent relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+ channels directly or via guanosine 3',5'-cyclic monophosphate, the present study investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc-GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was measured in rabbit carotid artery denuded of endothelium from normal and hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in normal and hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxations to the calcium channel blocker nifedipine were potentiated to a similar extent by charybdotoxin in both groups. In addition, arteries from hypercholesterolemic rabbits relaxed less than normal to sodium nitroprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.


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