Biomechanical Properties of Self-Assembly Tissue Engineered Blood Vessels: Insights Into Assembly Techniques

Author(s):  
Michael T. Zaucha ◽  
Rudolph Gleason

Coronary artery disease remains to be the leading cause of morbidity and mortality in industrialized nations. Current treatments for small diameter grafts are limited by the availability of suitable autologous vessels and high thrombogenic potential of synthetic grafts. There is a clinical need to development of tissue engineered blood vessels (TEBV) suitable for vascular by pass grafting.

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Maxime Y. Tondreau ◽  
Véronique Laterreur ◽  
Karine Vallières ◽  
Robert Gauvin ◽  
Jean-Michel Bourget ◽  
...  

There is a clinical need for tissue-engineered small-diameter (<6 mm) vascular grafts since clinical applications are halted by the limited suitability of autologous or synthetic grafts. This study uses the self-assembly approach to produce a fibroblast-derived decellularized vascular scaffold (FDVS) that can be available off-the-shelf. Briefly, extracellular matrix scaffolds were produced using human dermal fibroblasts sheets rolled around a mandrel, maintained in culture to allow for the formation of cohesive and three-dimensional tubular constructs, and decellularized by immersion in deionized water. The FDVSs were implanted as an aortic interpositional graft in six Sprague-Dawley rats for 6 months. Five out of the six implants were still patent 6 months after the surgery. Histological analysis showed the infiltration of cells on both abluminal and luminal sides, and immunofluorescence analysis suggested the formation of neomedia comprised of smooth muscle cells and lined underneath with an endothelium. Furthermore, to verify the feasibility of producing tissue-engineered blood vessels of clinically relevant length and diameter, scaffolds with a 4.6 mm inner diameter and 17 cm in length were fabricated with success and stored for an extended period of time, while maintaining suitable properties following the storage period. This novel demonstration of the potential of the FDVS could accelerate the clinical availability of tissue-engineered blood vessels and warrants further preclinical studies.


2010 ◽  
Vol 8 (55) ◽  
pp. 244-256 ◽  
Author(s):  
Michael T. Zaucha ◽  
Robert Gauvin ◽  
Francois A. Auger ◽  
Lucie Germain ◽  
Rudolph L. Gleason

Along with insights into the potential for graft success, knowledge of biomechanical properties of small diameter tissue-engineered blood vessel (TEBV) will enable designers to tailor the vessels' mechanical response to closer resemble that of native tissue. Composed of two layers that closely mimic the native media and adventitia, a tissue-engineered vascular adventitia (TEVA) is wrapped around a tissue-engineered vascular media (TEVM) to produce a self-assembled tissue-engineered media/adventia (TEVMA). The current study was undertaken to characterize the biaxial biomechanical properties of TEVM, TEVA and TEVMA under physiological pressures as well as characterize the stress-free reference configuration. It was shown that the TEVA had the greatest compliance over the physiological loading range while the TEVM had the lowest compliance. As expected, compliance of the SA-TEBV fell in between with an average compliance of 2.73 MPa −1 . Data were used to identify material parameters for a microstructurally motivated constitutive model. Identified material parameters for the TEVA and TEVM provided a good fit to experimental data with an average coefficient of determination of 0.918 and 0.868, respectively. These material parameters were used to develop a two-layer predictive model for the response of a TEVMA which fit well with experimental data.


Author(s):  
Krishna Madhavan ◽  
Walter Bonani ◽  
Craig Lanning ◽  
Wei Tan

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.


2008 ◽  
Vol 57 ◽  
pp. 226-234 ◽  
Author(s):  
Rudolph L. Gleason ◽  
William Wan

There is a great unmet clinical need to develop small diameter tissue engineered blood vessels (TEBV) with low thrombogenicity and immune response and suitable mechanical properties. In this paper we describe experimental and computational frameworks to characterize the use of mechanical stimuli to improve the mechanical properties of TEBVs. We model the TEBV as a constrained mixture and track the production, degradation, mechanical state, and organization of each structural constituent. Specifically, we assume that individual load bearing constituents can co-exist within each neighborhood and, although they are constrained to deform together, each constituent within this neighborhood may have different natural (i.e., stress-free) configurations. Motivated by this theoretical framework, we have designed a bioreactor and biomechanical testing device for TEBVs. This device is designed to provide precise and independent control of mean and cyclic luminal flow rate, transmural pressure, and axial load over weeks and months in culture and perform intermittent biaxial biomechanical tests. This device also fits under a two-photon laser scanning microscope for 3-dimenstional imaging of the content and organization of cells and matrix constituents. These data directly support our theoretical model.


2021 ◽  
Vol 26 (12) ◽  
pp. 4746
Author(s):  
A. N. Maltseva ◽  
A. V. Mochula ◽  
K. V. Kopyeva ◽  
E. V. Grakova ◽  
K. V. Zavadovsky

Non-obstructive coronary artery disease is generally considered as a favorable type of pathology, however, a number of studies indicate that in non-obstructive atherosclerosis, the risk of such cardiovascular events as myocardial infarction, ischemic stroke, sudden cardiac death and decompensated heart failure cannot be completely ruled out. This may be due to microvascular dysfunction. However, due to the small diameter of vessels, none of the imaging techniques used in clinical practice makes it possible to assess microvascular morphology. To date, the most well-established methods for assessing myocardial perfusion are single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The ability to quantify myocardial blood flow and coronary flow reserve allows SPECT and PET to be the methods of choice for non-invasive diagnosis of microvascular dysfunction. This review is devoted to current data on the clinical significance of radionuclide diagnosis of microvascular dysfunction in patients with non-obstructive coronary artery disease.


Vascular ◽  
2011 ◽  
Vol 19 (4) ◽  
pp. 206-213 ◽  
Author(s):  
Jian-De Dong ◽  
Jin-Hong Huang ◽  
Feng Gao ◽  
Zhao-Hui Zhu ◽  
Jian Zhang

The aim of the study was to construct small-diameter vascular grafts using canine mesenchymal stem cells (cMSCs) and a pulsatile flow bioreactor. cMSCs were isolated from canine bone marrow and expanded ex vivo. cMSCs were then seeded onto the luminal surface of decellularized arterial matrices, which were further cultured in a pulsatile flow bioreactor for four days. Immunohistochemical staining and scanning electron microscopy was performed to characterize the tissue-engineered blood vessels. cMSCs were successfully seeded onto the luminal surface of porcine decellularized matrices. After four-day culture in the pulsatile flow bioreactor, the cells were highly elongated and oriented to the flow direction. Immunohistochemistry demonstrated that the cells cultured under pulsatile flow expressed Von Willebrand factor, an endothelial cell marker. In conclusion, cMSCs seeded onto decellularized arterial matrices could differentiate into endothelial lineage after culturing in a pulsatile flow bioreactor, which provides a novel approach for tissue engineering of small-diameter blood vessels.


2014 ◽  
Author(s):  
◽  
Ashkan Shafiee

Tissue engineering and regenerative medicine may help to save people’s lives by fabricating new organs. Towards this goal our objective is to optimize the conditions for cells to self assemble into functional structures, such as tissues and eventually organoids. To facilitate self-assembly we employ the technology of bioprinting. To maintain the extended cellular assemblies, they need to be vascularized. Thus we first concentrated on the fabrication of blood vessels. We prepared convenient bioink particles, multicellular units composed of the relevant cell types and we deposited them into a configuration, consistent with the shape of the vessel. Self-assembly and the maturation of the construct takes place post-printing in special-purpose bioreactors by the fusion of the bioink units and the rearrangement of the cells within them. The time to achieve near physiological biomechanical properties has so far been found by trial and error. We report the experimental part of an experimental-theoretical-computational framework to optimize the postprinting maturation process, in particular the fusion of the bioink units. The connection between experiments and computer simulations were guided by theory. Here we report the results of extended fusion experiments and on their comparison with predictions of the theory. The excellent agreement we found, on one hand, provided a verification of the theoretical component of the formalism, and, on the other hand, the input for the computational component of the formalism. Specifically, our experiments, together with the theory, allowed the calibration of the basic simulation parameters, which in turn allows the full implementation of the computational component of the formalism to optimize the fabrication of blood vessels through the bioprinting process.


2021 ◽  
Vol 2145 (1) ◽  
pp. 012037
Author(s):  
A Sukchanta ◽  
P Kummanee ◽  
W Nuansing

Abstract The small diameter artificial blood vessel is synthesized with a diameter less than or equal to 6 millimetres. This technique has been used in coronary artery bypass grafting to treat coronary artery disease. Currently, the problem of coronary artery disease is still common, in addition to aortic aneurysm caused by the incompatibility of mechanical properties between the artificial blood vessel and the local blood vessel in the patient’s body. This research aims to solve the aforementioned problems using electrospinning and 3D printing technologies, as many types of materials are supported, all parameters are easy to change, and the cost is low. In this report, we describe a design for a small diameter polylactic acid (PLA) vascular graft fabricated by electrospinning with solutions of PLA in AC/DMF (1:1) 10, 12 and 15% w/v at 4 mm. The electrospun PLA nanofibers are tested for their morphology, contact angle, and seam strength. As the results, the fibres are still no same direction alignment due to insufficient rotation speed. The filament holding force is in the range of 1.90-2.71 N and the contact angles are greater than 90° because the samples are not wettable and have hydrophobic property. Further on, we will investigate other required properties, such as cell culture and other mechanical properties. Furthermore, we will compare the results with 3D printed artificial blood vessels with small diameter.


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