scholarly journals Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts

2021 ◽  
Vol 11 (10) ◽  
pp. 4563
Author(s):  
Yuichi Matsuzaki ◽  
Anudari Ulziibayar ◽  
Toshihiro Shoji ◽  
Toshiharu Shinoka
Keyword(s):  
Cardiovascular Surgery ◽  
Thrombus Formation ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Clinical Applications ◽  
Biodegradable Materials ◽  
Large Animal ◽  
Arterial Grafts ◽  
Large Animal Models

The creation of small-diameter tissue-engineered vascular grafts using biodegradable materials has the potential to change the quality of cardiovascular surgery in the future. The implantation of these tissue-engineered arterial grafts has yet to reach clinical application. One of the reasons for this is thrombus occlusion of the graft in the acute phase. In this paper, we first describe the causes of accelerated thrombus formation and discuss the drugs that are thought to inhibit thrombus formation. We then review the latest research on methods to locally bind the anticoagulant heparin to biodegradable materials and methods to extend the duration of sustained heparin release. We also discuss the results of studies using large animal models and the challenges that need to be overcome for future clinical applications.

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

Cells ◽  
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.

scholarly journals Therapeutic Resevoirs: Implantable Therapeutic Reservoir Systems for Diverse Clinical Applications in Large Animal Models (Adv. Healthcare Mater. 11/2020)

2020 ◽  
Vol 9 (11) ◽  
pp. 2070035
Author(s):  
Garry P. Duffy ◽  
Scott T. Robinson ◽  
Raymond O'Connor ◽  
Robert Wylie ◽  
Ciaran Mauerhofer ◽  
...  
Keyword(s):  
Animal Models ◽  
Clinical Applications ◽  
Large Animal ◽  
Large Animal Models ◽  
Reservoir Systems

scholarly journals Implantable Therapeutic Reservoir Systems for Diverse Clinical Applications in Large Animal Models

2020 ◽  
Vol 9 (11) ◽  
pp. 2000305 ◽  
Author(s):  
Garry P. Duffy ◽  
Scott T. Robinson ◽  
Raymond O'Connor ◽  
Robert Wylie ◽  
Ciaran Mauerhofer ◽  
...  
Keyword(s):  
Animal Models ◽  
Clinical Applications ◽  
Large Animal ◽  
Large Animal Models ◽  
Reservoir Systems

Different degradation rates of nanofiber vascular grafts in small and large animal models

2020 ◽  
Vol 14 (2) ◽  
pp. 203-214
Author(s):  
Takuma Fukunishi ◽  
Chin Siang Ong ◽  
Pooja Yesantharao ◽  
Cameron A. Best ◽  
Tai Yi ◽  
...  
Keyword(s):  
Animal Models ◽  
Vascular Grafts ◽  
Large Animal ◽  
Large Animal Models ◽  
Degradation Rates

scholarly journals IL-1 in osteoarthritis: time for a critical review of the literature

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 934 ◽  
Author(s):  
Tonia L. Vincent
Keyword(s):  
Interleukin 1 ◽  
Cartilage Degradation ◽  
Large Animal ◽  
Therapeutic Approaches ◽  
Double Blind ◽  
Potent Inducer ◽  
Large Animal Models ◽  
Randomised Controlled

The concept of interleukin-1 (IL-1) as a target in osteoarthritis (OA) has been an attractive one for many years. It is a highly potent inducer of cartilage degradation, causing the induction of mRNA and controlling the bioavailability of disease-relevant proteases such as ADAMTS5 and MMP13. It drives synovitis and can induce other disease-relevant genes such as nerve growth factor, a key pain sensitiser in OA. However, the quality of evidence for its involvement in disease is modest. Descriptive studies have demonstrated expression of IL-1α and β in OA cartilage and elevated levels in the synovial fluid of some patients. Agnostic transcriptomic and genomic analyses do not identify IL-1 as a key pathway.In vivomodels show a conflicting role for this molecule; early studies using therapeutic approaches in large animal models show a benefit, but most murine studies fail to demonstrate protection where the ligands (IL-1α/β), the cytokine activator (IL-1–converting enzyme), or the receptor (IL-1R) have been knocked out. Recently, a number of large double-blind randomised controlled clinical studies targeting IL-1 have failed. Enthusiasm for IL-1 as a target in OA is rapidly dwindling.

Engineering blood vessels and vascularized tissues: technology trends and potential clinical applications

2019 ◽  
Vol 133 (9) ◽  
pp. 1115-1135 ◽  
Author(s):  
Prafulla Chandra ◽  
Anthony Atala
Keyword(s):  
Tissue Engineering ◽  
Vascular Tissue ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Clinical Applications ◽  
Angiogenic Factors ◽  
Vascular Tissue Engineering ◽  
Technology Trends

Abstract Vascular tissue engineering has the potential to make a significant impact on the treatment of a wide variety of medical conditions, including providing in vitro generated vascularized tissue and organ constructs for transplantation. Since the first report on the construction of a biological blood vessel, significant research and technological advances have led to the generation of clinically relevant large and small diameter tissue engineered vascular grafts (TEVGs). However, developing a biocompatible blood-contacting surface is still a major challenge. Researchers are using biomimicry to generate functional vascular grafts and vascular networks. A multi-disciplinary approach is being used that includes biomaterials, cells, pro-angiogenic factors and microfabrication technologies. Techniques to achieve spatiotemporal control of vascularization include use of topographical engineering and controlled-release of growth/pro-angiogenic factors. Use of decellularized natural scaffolds has gained popularity for engineering complex vascularized organs for potential clinical use. Pre-vascularization of constructs prior to implantation has also been shown to enhance its anastomosis after implantation. Host-implant anastomosis is a phenomenon that is still not fully understood. However, it will be a critical factor in determining the in vivo success of a TEVGs or bioengineered organ. Many clinical studies have been conducted using TEVGs, but vascularized tissue/organ constructs are still in the research & development stage. In addition to technical challenges, there are commercialization and regulatory challenges that need to be addressed. In this review we examine recent advances in the field of vascular tissue engineering, with a focus on technology trends, challenges and potential clinical applications.

Basic Mechanisms of Arterial and Venous Thrombosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-1-SCI-1
Author(s):  
Thomas Renné
Keyword(s):  
Conflicts Of Interest ◽  
Thrombus Formation ◽  
Contact System ◽  
Large Animal ◽  
Inflammatory Disorder ◽  
Factor Xii ◽  
Kinin System ◽  
Large Animal Models

Abstract Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. Factor XII (FXII, Hageman factor) is a plasma protease that initiates the contact system. This system starts a cascade of procoagulant and proinflammatory reactions via the intrinsic pathway of coagulation, and the bradykinin producing kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood, however its in vivo functions are just beginning to emerge. This presentation will summarize roles of the FXII-driven contact system in vivo. Genetically altered mice and large animal models have shown that FXII is essential for thrombus formation while being dispensable for hemostatic processes that terminate blood loss. Challenging the dogma of a coagulation balance, targeting FXII protected from cerebral ischemia without interfering with hemostasis. In contrast, excess FXII activity is associated with a life threatening inflammatory disorder, hereditary angioedema. Platelet polyphosphate (an inorganic polymer), neutrophil extracellular traps (NETs) and mast cell heparin activate FXII with implications on the initiation of thrombosis and edema. A key aspect of the talk will be the analysis of common principles, interactions and cross-talk between coagulation and inflammation, and the use of the novel FXII blocking antibody 3F7 in cardiopulmonary bypass system. Elucidating the FXII-driven contact system offers the exciting opportunity to develop strategies for safe interference with both thrombotic and inflammatory diseases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Approaches to antithrombotic modification of vascular implants

2020 ◽  
Vol 101 (2) ◽  
pp. 232-242
Author(s):  
V V Sevostyanova ◽  
E O Krivkina ◽  
L V Antonova
Keyword(s):  
Blood Vessel ◽  
New Technologies ◽  
Vascular Tissue ◽  
Thrombus Formation ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Biologically Active ◽  
Implant Surface ◽  
Endovascular Stents ◽  
Wide Range

Vascular implants in contact with blood must have high thrombotic resistance. However, in some cases, their implantation is associated with thrombosis and subsequent impaired patency of the blood vessel. Most often, this problem affects implants intended for reconstruction of small diameter vessels, which is associated with hemodynamic features in this part of the bloodstream. These include blood vessel prostheses, tissue-engineered vascular grafts, and endovascular stents. The features of the implant material are of great importance when choosing a method for its modification in order to improve biocompatibility and thromboresistance. The review analyzes current experience in using various methods of immobilizing drugs to the surface of vascular prostheses and endovascular stents made from stable and biodegradable polymers. The prospects of creating thromboresistant vascular grafts and stents by joint immobilization on the surface of the polymer material of drugs with antithrombogenic activity and biologically active molecules that regulate the reaction to a foreign body and implant remodeling were evaluated. Numerous studies in the review demonstrating a wide range of ways to modify blood vessel prostheses, tissue-engineered vascular grafts, and endovascular stents with antithrombotic drugs to increase their thrombosis resistance. The main approaches of antithrombotic modification include conjugation of drugs and biologically active molecules on the implant surface. At the same time, new technologies are aimed not only at inhibiting the process of thrombus formation, but also at reducing the intensity of the inflammation process and stimulating the reparation of vascular tissue.

Sign in / Sign up

Export Citation Format

Share Document