Acute Phase Pilot Evaluation of Small Diameter Long iBTA-Induced Vascular Graft “Biotube” in a Goat Model

Small diameter (<6 mm) vessel grafts still pose a challenge for scientists worldwide. Decellularised umbilical artery (dUA) remains promising as small diameter tissue engineered vascular graft (TEVG), yet their immunogenicity remains unknown. Herein, we evaluated the host immune responses, with a focus on the innate part, towards human dUA implantation in mice, and confirmed our findings in an ex vivo allogeneic human setup. Overall, we did not observe any differences in the number of circulating white blood cells nor the number of monocytes among three groups of mice (1) dUA patch; (2) Sham; and (3) Mock throughout the study (day −7 to 28). Likewise, we found no difference in systemic inflammatory and anti-inflammatory cytokine levels between groups. However, a massive local remodelling response with M2 macrophages were observed in the dUA at day 28, whereas M1 macrophages were less frequent. Moreover, human monocytes from allogeneic individuals were differentiated into macrophages and exposed to lyophilised dUA to maximize an eventual M1 response. Yet, dUA did not elicit any immediate M1 response as determined by the absence of CCR7 and CXCL10. Together this suggests that human dUA elicits a minimal pro-inflammatory response further supporting its use as a TEVG in an allogeneic setup.

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Design, Preparation, and Performance of a Novel Bilayer Tissue‐Engineered Small‐Diameter Vascular Graft

Macromolecular Bioscience ◽

10.1002/mabi.201800189 ◽

2018 ◽

Vol 19 (3) ◽

pp. 1800189 ◽

Cited By ~ 9

Author(s):

Xiaolin Ran ◽

Zhiyi Ye ◽

Meiling Fu ◽

Qilong Wang ◽

Haide Wu ◽

...

Keyword(s):

Vascular Graft ◽

Small Diameter ◽

And Performance

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Characterization of silk sponge in the wet state using13C solid state NMR for development of a porous silk vascular graft with small diameter

RSC Advances ◽

10.1039/c3ra45190a ◽

2014 ◽

Vol 4 (9) ◽

pp. 4427-4434 ◽

Cited By ~ 16

Author(s):

Tetsuo Asakura ◽

Toshiki Saotome ◽

Derya Aytemiz ◽

Haruka Shimokawatoko ◽

Takahito Yagi ◽

...

Keyword(s):

Solid State ◽

Solid State Nmr ◽

Vascular Graft ◽

Small Diameter

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Development and Biomechanical Characterization of a Novel Bilayer Vascular Graft

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19613 ◽

2010 ◽

Author(s):

Krishna Madhavan ◽

Walter Bonani ◽

Craig Lanning ◽

Wei Tan

Keyword(s):

Blood Vessel ◽

Vascular Graft ◽

Bypass Surgery ◽

Small Diameter ◽

Native Artery ◽

Vessel Lumen ◽

Unmet Demand ◽

Tissue Engineered Blood Vessels ◽

Synthetic Grafts

Vascular grafts are currently used to treat cardiovascular diseases such as arthrosclerosis by bypass surgery and as vascular access in hemodialysis [1]. There are a number of types of grafts including autologous vessels (such saphenous vein), synthetic grafts (such as expanded polytetrafluoroethylene) and tissue engineered blood vessels. Currently synthetic grafts are most commonly used as blood vessel replacements and there are a number of problems associated with them. One main impediment is that these grafts are not suitable for small-diameter (less than 6mm) vessel replacement [1, 2], due to high occlusion rates. The major concern over the other alternatives such as autologous vessels and tissue engineered products is their availability. Thus, new approaches to constructing biomimetic small-diameter blood vessel equivalents, that are immediately available, may address the unmet demand in this area. Therefore, we have designed a novel bilayer vascular construct which is made up of a nanofibrous intimal-equivalent as thromboresistant vessel lumen and a mimetic extracellular matrix (ECM) as medial-equivalent for smooth muscle cells (SMC) from native artery to invade and remodel the ECM.

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Endothelial cell monolayer formation on a small-diameter vascular graft surface under pulsatile flow conditions

Russian Journal of Transplantology and Artificial Organs ◽

10.15825/1995-1191-2021-3-101-114 ◽

2021 ◽

Vol 23 (3) ◽

pp. 101-114

Author(s):

M. Yu. Khanova ◽

E. A. Velikanova ◽

V. G. Matveeva ◽

E. O. Krivkina ◽

T. V. Glushkova ◽

...

Keyword(s):

Shear Stress ◽

Endothelial Cell ◽

Pulsatile Flow ◽

Vascular Graft ◽

Cell Monolayer ◽

Small Diameter ◽

Flow Conditions ◽

Endothelial Cell Culture ◽

Monolayer Formation ◽

Whole Transcriptome

Objective: to create a cell-populated small-diameter vascular graft (SDVG) using autologous endothelial cells and extracellular matrix proteins, and to evaluate the efficiency of endothelial cell monolayer formation during shear stress preconditioning in a SDVG.Materials and methods. PHBV/PCL tubular scaffolds of vascular grafts were made by electrospinning from a mixture of polyhydroxybutyrate-valerate (PHBV) copolymer and polycaprolactone (PCL) and modified with fibrin. To populate the graft, an endothelial cell culture was isolated from the blood of patients with coronary heart disease. Phenotyping of endothelial colony-forming cell (ECFC) culture was performed by flow cytometry and immunofluorescence microscopy. Cell proliferative and angiogenic activity were also studied. Cell-populated vascular scaffolds were cultured in a pulsatile flow setup with a final shear stress of 2.85 dyne/cm2. The effect of pulsatile flow on monolayer formation was assessed by immunofluorescence, scanning electron microscopy, atomic force microscopy, and whole-transcriptome RNA sequencing.Results. Under the influence of pulsatile flow, endothelial cells that were seeded into the tubular scaffold showed an increase in the expression level of endothelial profile proteins, focal adhesion and cytoskeleton. In contrast to endothelial cell culture on a vascular graft surface under static conditions, when cultured under pulsatile flow with 2.85 dyne/ cm2 shear stress, endothelial lining cells have an increased ability to adhere and are oriented along the pulsatile flow path. Whole-transcriptome RNA sequencing showed that induced shear stress increased expression levels of differentially expressed genes encoding proteins that ensure vascular development, endothelial integrity, and endothelial metabolism. A protocol for fabrication of a personalized cell-populated biodegradable SDVG under pulsatile flow conditions was developed.Conclusion. The use of autologous fibrin and ECFC culture, as well as shear stress preconditioning, allow to obtain a personalized cell-populated SDVG with continuous functional endothelial monolayer adapted to the flow.

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Tissue ingrowth markedly reduces mechanical anisotropy and stiffness in fibre direction of highly aligned electrospun polyurethane scaffolds

10.1101/779942 ◽

2019 ◽

Cited By ~ 2

Author(s):

Hugo Krynauw ◽

Jannik Buescher ◽

Josepha Koehne ◽

Loes Verrijt ◽

Georges Limbert ◽

...

Keyword(s):

Elastic Modulus ◽

Vascular Graft ◽

Small Diameter ◽

Mechanical Anisotropy ◽

Fibre Direction ◽

Tissue Ingrowth ◽

Fibre Alignment ◽

Random Fibre ◽

Directed Research

AbstractPurposeThe lack of long-term patency of synthetic vascular grafts currently available on the market has directed research towards improving the performance of small diameter grafts. Improved radial compliance matching and tissue ingrowth into the graft scaffold are amongst the main goals for an ideal vascular graft.MethodsBiostable polyurethane scaffolds were manufactured by electrospinning and implanted in subcutaneous and circulatory positions in the rat for 7, 14 and 28 days. Scaffold morphology, tissue ingrowth, and mechanical properties of the scaffolds were assessed before implantation and after retrieval.ResultsTissue ingrowth after 24 days was 96.5 ± 2.3% in the subcutaneous implants and 77.8 ± 5.4% in the circulatory implants. Over the 24 days implantation, the elastic modulus at 12% strain decreased by 59% in direction of the fibre alignment whereas it increased by 1379% transverse to the fibre alignment of the highly aligned scaffold of the subcutaneous implants. The lesser aligned scaffold of the circulatory graft implants exhibited an increase of the elastic modulus at 12% strain by 77% in circumferential direction.ConclusionBased on the observations, it is proposed that the mechanism underlying the softening of the highly aligned scaffold in the predominant fibre direction is associated with scaffold compaction and local displacement of fibres by the newly formed tissue. The stiffening of the scaffold, observed transverse to highly aligned fibres and for more a random fibre distribution, represents the actual mechanical contribution of the tissue that developed in the scaffold.

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