Histological Reactions and the In Vivo Patency Rates of Small Silk Vascular Grafts in a Canine Model

Purpose: When arteriovenous (AV) fistula is not feasible for vascular access in most patients on hemodialysis, the second choice is interposition AV fistula using synthetic graft. However, the grafts pose risks such as infection and low patency. Therefore, we created in vivo tissue-engineered “Biotube” vascular grafts formed with autologous tissue, based on the tissue encapsulation phenomenon. Previously, we confirmed that vascular-like structure was reconstructed in implanted Biotubes with year-ordered patency in vivo. In this study, we evaluated whether Biotubes could replace vascular access grafts for hemodialysis in the cervical vessels of beagles. Methods and Results: The mold for Biotube preparation was assembled by inserting a silicone rod (external diameter 4 mm; length 50 mm) into an acrylate tubular cover (internal diameter 6 mm; length 50 mm with several longitudinal slits). The molds were embedded into the dorsal subcutaneous pouches of beagles (n=3) for 4 weeks, after which they were harvested by a minimally invasive technique from the same incision (width ca. 20 mm). After removing the molds, Biotubes formed by tissue migration to a silicone surface through the mold slits (internal diameter 4 mm; length 45 mm; wall thickness ca. 1 mm) were obtained. Biotubes were then bypassed between the carotid artery (side-to-end anastomosis) and jugular vein (end-to-end anastomosis) of anesthetized beagles. Following placement of Biotubes, continuous thrill was felt by palpation and ultrasound showed turbulent blood flow. After one month, angiography showed no stenosis, elongation, or hemorrhage in any Biotubes. Percutaneous puncturing with a needle, blood removal and resupply from the needle, and astirction within several minutes were feasible. Conclusions: In our beagle model, Biotubes successfully created an AV shunt that maintained steady blood flow, suggesting that Biotubes have potential clinical use in maintaining vascular access for hemodialysis.

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Antithrombogenic surface modifications in xenogenic pericardial vascular grafts: Initial in-vivo evaluation

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0030-1269233 ◽

2011 ◽

Vol 59 (S 01) ◽

Author(s):

J Linneweber ◽

F Voss ◽

P Dohmen ◽

W Erdbrügger ◽

W Konertz

Keyword(s):

Vascular Grafts ◽

Surface Modifications ◽

In Vivo Evaluation

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Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646468 ◽

1991 ◽

Vol 66 (05) ◽

pp. 609-613 ◽

Cited By ~ 14

Author(s):

I R MacGregor ◽

J M Ferguson ◽

L F McLaughlin ◽

T Burnouf ◽

C V Prowse

Keyword(s):

High Purity ◽

Time Course ◽

Prothrombin Complex Concentrate ◽

Degradation Products ◽

Canine Model ◽

Factor Ix ◽

In Vitro Tests ◽

Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

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The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651541 ◽

1993 ◽

Vol 69 (01) ◽

pp. 021-024 ◽

Cited By ~ 20

Author(s):

Shawn Tinlin ◽

Sandra Webster ◽

Alan R Giles

Keyword(s):

Factor Viii ◽

Canine Model ◽

Significant Inhibition ◽

Human Condition ◽

Haemophilia A ◽

Variable Expression ◽

The Family ◽

Over Time

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.

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Surface Modification by Nanobiomaterials for Vascular Tissue Engineering Applications

Current Medicinal Chemistry ◽

10.2174/0929867325666180914104633 ◽

2020 ◽

Vol 27 (10) ◽

pp. 1634-1646 ◽

Cited By ~ 1

Author(s):

Huey-Shan Hung ◽

Shan-hui Hsu

Keyword(s):

Tissue Engineering ◽

Vascular Tissue ◽

Thrombus Formation ◽

Vascular Grafts ◽

Vascular Tissue Engineering ◽

Great Success ◽

Natural Polymers ◽

Vascular Biomaterials

Treatment of cardiovascular disease has achieved great success using artificial implants, particularly synthetic-polymer made grafts. However, thrombus formation and restenosis are the current clinical problems need to be conquered. New biomaterials, modifying the surface of synthetic vascular grafts, have been created to improve long-term patency for the better hemocompatibility. The vascular biomaterials can be fabricated from synthetic or natural polymers for vascular tissue engineering. Stem cells can be seeded by different techniques into tissue-engineered vascular grafts in vitro and implanted in vivo to repair the vascular tissues. To overcome the thrombogenesis and promote the endothelialization effect, vascular biomaterials employing nanotopography are more bio-mimic to the native tissue made and have been engineered by various approaches such as prepared as a simple surface coating on the vascular biomaterials. It has now become an important and interesting field to find novel approaches to better endothelization of vascular biomaterials. In this article, we focus to review the techniques with better potential improving endothelization and summarize for vascular biomaterial application. This review article will enable the development of biomaterials with a high degree of originality, innovative research on novel techniques for surface fabrication for vascular biomaterials application.

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Leukocyte Adhesion to the Coronary Microvasculature During Ischemia and Reperfusion in an In Vivo Canine Model

Circulation ◽

10.1161/01.cir.93.10.1784 ◽

1996 ◽

Vol 93 (10) ◽

pp. 1784-1787 ◽

Cited By ~ 55

Author(s):

Frank M. Sheridan ◽

Paul G. Cole ◽

David Ramage

Keyword(s):

Leukocyte Adhesion ◽

Canine Model ◽

Ischemia And Reperfusion

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Electrospun PLGA and PLGA/gelatin scaffolds for tubularized urethral replacement: Studies in vitro and in vivo

Journal of Biomaterials Applications ◽

10.1177/08853282211030904 ◽

2021 ◽

pp. 088532822110309

Author(s):

Jinhua Hu ◽

Bin Ai ◽

Shibo Zhu ◽

Zhen Wang ◽

Huimin Xia ◽

...

Keyword(s):

Tensile Deformation ◽

Canine Model ◽

Urothelial Cells ◽

Acellular Matrix ◽

Urethral Strictures ◽

Acid Copolymer ◽

Hematoxylin Eosin ◽

Collagen Tissue

To investigate the biocompatibility of polylactic acid-glycolic acid copolymer (PLGA) and PLGA/gelatin scaffolds and their suitability for tubular urethral replacement in a canine model. PLGA and PLGA/gelatin scaffolds was constructed by electrospinning. Microstructural differences between the scaffolds was examined by Scanning electron microscopy (SEM) followed by mechanical properties testing. Biocompatibility of the material was evaluated using SEM 4, 8, 12 and 72 h after PLGA and PLGA/gelatin scaffolds co-culture with urothelial cells. And confocal analysis was also used to showed the cell adhesive and growth at 12 h. Approximately 2 cm of the anterior urethra of twelve dogs were removed and replaced with a scaffold. After the surgery for 1 month performed urethrography and for 3 month perform hematoxylin–eosin (H&E) and Masson. The results indicated that PLGA and PLGA/gelatin scaffolds had a void microfilament structure, similar to that of normal acellular matrix tissue. And the tensile strength was decreased whereas the tensile deformation and suture retention strength was increased in PLGA/gelatin scaffolds compared to that in PLGA scaffolds Urothelial cells grew well on both scaffolds. Postoperatively, animals recovered well and urinated spontaneously. However, urethrography showed varying degrees of urethral strictures in the reconstructed urethras. H&E and Masson showed that multilayer urothelial cells were formed in both the proximal and distal segments of the reconstructed urethras but without continuity. There was a small amount of smooth muscle and blood vessels under the epithelium, but regenerative urothelial cells at the midpoint of the reconstructed segment did not continue. Lots of lymphocyte infiltration was observed under the epithelium, some collagen tissue was deposited under the neo-urethral epithelium were observed. In conclusion, PLGA and PLGA/gelatin scaffolds are not suitable for tubularized urethral replacement in the canine model.

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Assessment of Electrospun Pellethane-Based Scaffolds for Vascular Tissue Engineering

Materials ◽

10.3390/ma14133678 ◽

2021 ◽

Vol 14 (13) ◽

pp. 3678

Author(s):

Vera Chernonosova ◽

Alexandr Gostev ◽

Ivan Murashov ◽

Boris Chelobanov ◽

Andrey Karpenko ◽

...

Keyword(s):

Vascular Tissue ◽

Ex Vivo ◽

Vascular Grafts ◽

Wistar Rat ◽

Graft Occlusion ◽

Suitable Candidate ◽

Large Animals ◽

Cell Adhesion And Proliferation

We examined the physicochemical properties and the biocompatibility and hemocompatibility of electrospun 3D matrices produced using polyurethane Pellethane 2363-80A (Pel-80A) blends Pel-80A with gelatin or/and bivalirudin. Two layers of vascular grafts of 1.8 mm in diameter were manufactured and studied for hemocompatibility ex vivo and functioning in the infrarenal position of Wistar rat abdominal aorta in vivo (n = 18). Expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar diameter were implanted as a control (n = 18). Scaffolds produced from Pel-80A with Gel showed high stiffness with a long proportional limit and limited influence of wetting on mechanical characteristics. The electrospun matrices with gelatin have moderate capacity to support cell adhesion and proliferation (~30–47%), whereas vascular grafts with bivalirudin in the inner layer have good hemocompatibility ex vivo. The introduction of bivalirudin into grafts inhibited platelet adhesion and does not lead to a change hemolysis and D-dimers concentration. Study in vivo indicates the advantages of Pel-80A grafts over ePTFE in terms of graft occlusion, calcification level, and blood velocity after 6 months of implantation. The thickness of neointima in Pel-80A–based grafts stabilizes after three months (41.84 ± 20.21 µm) and does not increase until six months, demonstrating potential for long-term functioning without stenosis and as a suitable candidate for subsequent preclinical studies in large animals.

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Review: Tissue Engineering of Small-Diameter Vascular Grafts and Their In Vivo Evaluation in Large Animals and Humans

Cells ◽

10.3390/cells10030713 ◽

2021 ◽

Vol 10 (3) ◽

pp. 713

Author(s):

Shu Fang ◽

Ditte Gry Ellman ◽

Ditte Caroline Andersen

Keyword(s):

Animal Models ◽

Vascular Grafts ◽

Small Diameter ◽

Large Animal ◽

Large Animal Models ◽

Graft Outcome ◽

Limited Success ◽

Large Animals

To date, a wide range of materials, from synthetic to natural or a mixture of these, has been explored, modified, and examined as small-diameter tissue-engineered vascular grafts (SD-TEVGs) for tissue regeneration either in vitro or in vivo. However, very limited success has been achieved due to mechanical failure, thrombogenicity or intimal hyperplasia, and improvements of the SD-TEVG design are thus required. Here, in vivo studies investigating novel and relative long (10 times of the inner diameter) SD-TEVGs in large animal models and humans are identified and discussed, with emphasis on graft outcome based on model- and graft-related conditions. Only a few types of synthetic polymer-based SD-TEVGs have been evaluated in large-animal models and reflect limited success. However, some polymers, such as polycaprolactone (PCL), show favorable biocompatibility and potential to be further modified and improved in the form of hybrid grafts. Natural polymer- and cell-secreted extracellular matrix (ECM)-based SD-TEVGs tested in large animals still fail due to a weak strength or thrombogenicity. Similarly, native ECM-based SD-TEVGs and in-vitro-developed hybrid SD-TEVGs that contain xenogeneic molecules or matrix seem related to a harmful graft outcome. In contrast, allogeneic native ECM-based SD-TEVGs, in-vitro-developed hybrid SD-TEVGs with allogeneic banked human cells or isolated autologous stem cells, and in-body tissue architecture (IBTA)-based SD-TEVGs seem to be promising for the future, since they are suitable in dimension, mechanical strength, biocompatibility, and availability.

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