scholarly journals Bioactive coating for tissue-engineered smalldiameter vascular grafts

2021 ◽  
Vol 23 (4) ◽  
pp. 119-131
Author(s):  
V. A. Surguchenko ◽  
E. A. Nemets ◽  
V. Yu. Belov ◽  
V. I. Sevastianov
Keyword(s):  
Vascular Grafts ◽  
Small Diameter ◽  
Internal Surface ◽  
Internal Diameter ◽  
Bioactive Coating ◽  
Human Endothelial Cell Line ◽  
Copolymer Poly ◽  
Biopolymer Scaffolds

Objective: to develop a method for modifying composite small-diameter porous tubular biopolymer scaffolds based on bacterial copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and gelatin modified with a double-layered bioactive coating based on heparin (Hp) and platelet lysate (PL) that promote adhesion and proliferation of cell cultures.Materials and methods. Composite porous tubular biopolymer scaffolds with 4 mm internal diameter were made by electrospinning from a 1 : 2 (by volume) mixture of a 10% solution of poly(3-hydroxybutyrateco- 3-hydroxyvalerate) copolymer, commonly known as PHBV, and a 10% solution of gelatin, respectively, in hexafluoro-2-propanol. The structure of the scaffolds was stabilized with glutaraldehyde vapor. The scaffolds were modified with a bioactive Hp + PL-based coating. The surface morphology of the samples was analyzed using scanning electron microscopy. Biological safety of the modified scaffolds in vitro (hemolysis, cytotoxicity) was evaluated based on the GOST ISO 10993 standard. Interaction with cultures of human endothelial cell line (EA. hy926) and human adipose-derived mesenchymal stem cells (hADMSCs) was studied using vital dyes.Results. We developed a method for modifying small-diameter composite porous tubular biopolymer scaffolds obtained by electrospinning from a mixture of PHBV and gelatin modified with double-layered bioactive coating based on covalently immobilized Hp and human PL. The modified scaffold was shown to have no cytotoxicity and hemolytic activity in vitro. It was also demonstrated that the developed coating promotes hADMSC adhesion and proliferation on the external surface and EA.hy926 on the internal surface of the composite porous tubular biopolymer scaffolds in vitro.Conclusion. The developed coating can be used for the formation of in vivo tissueengineered small-diameter vascular grafts.

scholarly journals BIODEGRADABLE VASCULAR GRAFT MODIFIED BY RGD-PEPTIDES: EXPERIMENTAL RESEARCH

2019 ◽  
Vol 34 (2) ◽  
pp. 129-137
Author(s):  
E. O. Krivkina ◽  
V. N. Silnikov ◽  
A. V. Mironov ◽  
E. A. Velikanova ◽  
E. A. Senokosova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Internal Surface ◽  
Mechanical Tests ◽  
Laboratory Animals ◽  
Rgd Peptides ◽  
Peptide Modification

Research goals. To study the effectiveness of RGD-peptide modification of the small-diameter biodegradable vascular grafts depending on the type of a linker and RGD configuration.Material and Methods. Tubular scaffolds with a diameter of 1.5 and 4.0 mm were produced by electrospinning from polyhydroxybutyrate/valerate (PHBV) and polycaprolactone (PCL). The PHBV/PCL grafts were modified with RGD peptides. In vitro experiments showed the degree of erythrocyte hemolysis and adhesion of the platelets and endothelial cells when in contact with a modified surface. The physico-mechanical properties and the structure of graft surface were studied before and after modification. The PHBV/PCL and PHBV/PCL/RGD vascular grafts were implanted into the abdominal aorta of rats for the periods of 1 and 3 months. Explant samples were studied using confocal microscopy and histological methods.Results. The results of physical and mechanical tests showed a significant decrease in the strength properties of the PHBV/PCL/RGD grafts relative to the unmodified analogs. A significant increase in platelet aggregation was found in the modified grafts. The level of adhesion of the endothelial cells on the modified surfaces was higher than that on the unmodified surfaces. Shortterm implantation of the grafts for 1 and 3 months showed that the modified grafts had higher patency and a less tendency to calcification compared with the unmodified grafts. Immunofluorescence study demonstrated the significant superiority of the modified vascular grafts in terms of stimulating the formation of a mature endothelial monolayer. A longer linker of 4,7,10-trioxa-1,13-tridecane diamine was found to increase the bioavailability of RGD peptides; the use of RGDK and c[RGDFK] for surface modification of the grafts stimulated early endothelialization of the internal surface of the implants and reduced the prosthetic wall calcification tendency, which together increased the patency of the implanted grafts.Conclusion. In short-term implantation of biodegradable vascular grafts modified with RGD peptides, the grafts with RGDK and c[RGDFK], attached to the surface of the prostheses through the 4,7,10-triox-1,13-tridecane diamine linker, showed the best results in terms of endothelial adhesion and maintenance of the viability of the endothelial cells in vitro and endothelialization in vivo; these grafts had high patency after implantation into the bloodstream of small laboratory animals and a less tendency to calcification.

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.

Insight on the endothelialization of small silk-based tissue-engineered vascular grafts

2020 ◽  
Vol 43 (10) ◽  
pp. 631-644 ◽  
Author(s):  
Justine Cordelle ◽  
Sara Mantero
Keyword(s):  
Cell Adhesion ◽  
Vascular Tissue ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Graft Patency ◽  
Ongoing Research ◽  
The Right ◽  
And Behavior

Along with an increased incidence of cardiovascular diseases, there is a strong need for small-diameter vascular grafts. Silk has been investigated as a biomaterial to develop such grafts thanks to different processing options. Endothelialization was shown to be extremely important to ensure graft patency and there is ongoing research on the development and behavior of endothelial cells on vascular tissue-engineered scaffolds. This article reviews the endothelialization of silk-based scaffolds processed throughout the years as silk non-woven nets, films, gel spun, electrospun, or woven scaffolds. Encouraging results were reported with these scaffolds both in vitro and in vivo when implanted in small- to middle-sized animals. The use of coatings and heparin or sulfur to enhance, respectively, cell adhesion and scaffold hemocompatibility is further presented. Bioreactors also showed their interest to improve cell adhesion and thus promoting in vitro pre-endothelialization of grafts even though they are still not systematically used. Finally, the importance of the animal models used to study the right mechanism of endothelialization is discussed.

scholarly journals Controllable synthesis of biomimetic nano/submicro-fibrous tubes for potential small-diameter vascular grafts

2020 ◽  
Vol 8 (26) ◽  
pp. 5694-5706
Author(s):  
Yizao Wan ◽  
Shanshan Yang ◽  
Mengxia Peng ◽  
Miguel Gama ◽  
Zhiwei Yang ◽  
...  
Keyword(s):  
Cellulose Acetate ◽  
Bacterial Cellulose ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Controllable Synthesis ◽  
Small Diameter Vascular Grafts

A novel small-diameter graft consisting of nanofibrous bacterial cellulose and submicrofibrous cellulose acetate was prepared and evaluated in vitro and in vivo.

scholarly journals In Vivo Performance of Decellularized Vascular Grafts: A Review Article

2018 ◽  
Vol 19 (7) ◽  
pp. 2101 ◽  
Author(s):  
Chih-Hsun Lin ◽  
Kai Hsia ◽  
Hsu Ma ◽  
Hsinyu Lee ◽  
Jen-Her Lu
Keyword(s):  
Vascular Grafts ◽  
Small Diameter ◽  
Vascular Wall ◽  
Current Status ◽  
Preclinical Studies ◽  
Engineering Research ◽  
Cellular Inflammation ◽  
Surface Modified

Due to poor vessel quality in patients with cardiovascular diseases, there has been an increased demand for small-diameter tissue-engineered blood vessels that can be used as replacement grafts in bypass surgery. Decellularization techniques to minimize cellular inflammation have been applied in tissue engineering research for the development of small-diameter vascular grafts. The biocompatibility of allogenic or xenogenic decellularized matrices has been evaluated in vitro and in vivo. Both short-term and long-term preclinical studies are crucial for evaluation of the in vivo performance of decellularized vascular grafts. This review offers insight into the various preclinical studies that have been performed using decellularized vascular grafts. Different strategies, such as surface-modified, recellularized, or hybrid vascular grafts, used to improve neoendothelialization and vascular wall remodeling, are also highlighted. This review provides information on the current status and the future development of decellularized vascular grafts.

scholarly journals Design and Characterization of a Fluidic Device for the Evaluation of SIS-Based Vascular Grafts

Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1198
Author(s):  
Alejandra Riveros ◽  
Monica Cuellar ◽  
Paolo F. Sánchez ◽  
Carolina Muñoz-Camargo ◽  
Juan C. Cruz ◽  
...  
Keyword(s):  
Flow Regime ◽  
In Silico ◽  
Umbilical Vein ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Clinical Implementation ◽  
Cfd Validation ◽  
Pulsatile Pressure

Currently available small diameter vascular conduits present several long-term limitations, which has prevented their full clinical implementation. Commercially available vascular grafts show no regenerative capabilities and eventually require surgical replacement; therefore, it is of great interest to develop alternative regenerative vascular grafts (RVG). Decellularized Small Intestinal Submucosa (SIS) is an attractive material for RVG, however, the evaluation of the performance of these grafts is challenging due to the absence of devices that mimic the conditions found in vivo. Thereby, the objective of this study is to design, manufacture and validate in silico and in vitro, a novel fluidic system for the evaluation of human umbilical vein endothelial cells (HUVECs) proliferation on SIS-based RVG under dynamical conditions. Our perfusion and rotational fluidic system was designed in Autodesk Inventor 2018. In silico Computational Fluid Dynamics (CFD) validation of the system was carried out using Ansys Fluent software from ANSYS, Inc for dynamical conditions of a pulsatile pressure function measured experimentally over a rigid wall model. Mechanical and biological parameters such as flow regime, pressure gradient, wall shear stress (WSS), sterility and indirect cell viability (MTT assay) were also evaluated. Cell adhesion was confirmed by SEM imaging. The fluid flow regime within the system remains laminar. The system maintained sterility and showed low cytotoxicity levels. HUVECs were successfully cultured on SIS-based RVG under both perfusion and rotation conditions. In silico analysis agreed well with our experimental and theoretical results, and with recent in vitro and in vivo reports for WSS. The system presented is a tool for evaluating RVG and represents an alternative to develop new methods and protocols for a more comprehensive study of regenerative cardiovascular devices.

scholarly journals Acellular Small-Diameter Tissue-Engineered Vascular Grafts

2019 ◽  
Vol 9 (14) ◽  
pp. 2864 ◽  
Author(s):  
Zhen Li ◽  
Xinda Li ◽  
Tao Xu ◽  
Lei Zhang
Keyword(s):  
Effective Means ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Test Results ◽  
In Vivo Test ◽  
Current State

Tissue-engineered vascular grafts (TEVGs) are considered one of the most effective means of fabricating vascular grafts. However, for small-diameter TEVGs, there are ongoing issues regarding long-term patency and limitations related to long-term in vitro culture and immune reactions. The use of acellular TEVG is a more convincing method, which can achieve in situ blood vessel regeneration and better meet clinical needs. This review focuses on the current state of acellular TEVGs based on scaffolds and gives a summary of the methodologies and in vitro/in vivo test results related to acellular TEVGs obtained in recent years. Various strategies for improving the properties of acellular TEVGs are also discussed.

scholarly journals Biocompatibility of Small-Diameter Vascular Grafts in Different Modes of RGD Modification

Polymers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 174 ◽  
Author(s):  
Larisa Antonova ◽  
Vladimir Silnikov ◽  
Victoria Sevostyanova ◽  
Arseniy Yuzhalin ◽  
Lyudmila Koroleva ◽  
...  
Keyword(s):  
Vascular Grafts ◽  
Small Diameter ◽  
Primary Patency ◽  
Rgd Peptides ◽  
Vascular Prostheses ◽  
Sequence Composition ◽  
Rgd Sequence ◽  
Linker Group

Modification with Arg-Gly-Asp (RGD) peptides is a promising approach to improve biocompatibility of small-calibre vascular grafts but it is unknown how different RGD sequence composition impacts graft performance. Here we manufactured 1.5 mm poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) grafts modified by distinct linear or cyclic RGD peptides immobilized by short or long amine linker arms. Modified vascular prostheses were tested in vitro to assess their mechanical properties, hemocompatibility, thrombogenicity and endothelialisation. We also implanted these grafts into rat abdominal aortas with the following histological examination at 1 and 3 months to evaluate their primary patency, cellular composition and detect possible calcification. Our results demonstrated that all modes of RGD modification reduce ultimate tensile strength of the grafts. Modification of prostheses does not cause haemolysis upon the contact with modified grafts, yet all the RGD-treated grafts display a tendency to promote platelet aggregation in comparison with unmodified counterparts. In vivo findings identify that cyclic Arg-Gly-Asp-Phe-Lys peptide in combination with trioxa-1,13-tridecanediamine linker group substantially improve graft biocompatibility. To conclude, here we for the first time compared synthetic small-diameter vascular prostheses with different modes of RGD modification. We suggest our graft modification regimen as enhancing graft performance and thus recommend it for future use in tissue engineering.

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.

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