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      Decellularized blood vessel development: Current state-of-the-art and future directions

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          Abstract

          Vascular diseases contribute to intensive and irreversible damage, and current treatments include medications, rehabilitation, and surgical interventions. Often, these diseases require some form of vascular replacement therapy (VRT) to help patients overcome life-threatening conditions and traumatic injuries annually. Current VRTs rely on harvesting blood vessels from various regions of the body like the arms, legs, chest, and abdomen. However, these procedures also produce further complications like donor site morbidity. Such common comorbidities may lead to substantial pain, infections, decreased function, and additional reconstructive or cosmetic surgeries. Vascular tissue engineering technology promises to reduce or eliminate these issues, and the existing state-of-the-art approach is based on synthetic or natural polymer tubes aiming to mimic various types of blood vessel. Burgeoning decellularization techniques are considered as the most viable tissue engineering strategy to fill these gaps. This review discusses various approaches and the mechanisms behind decellularization techniques and outlines a simplified model for a replacement vascular unit. The current state-of-the-art method used to create decellularized vessel segments is identified. Also, perspectives on future directions to engineer small- (inner diameter >1 mm and <6 mm) to large-caliber (inner diameter >6 mm) vessel substitutes are presented.

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          Most cited references118

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          An overview of tissue and whole organ decellularization processes.

          Biologic scaffold materials composed of extracellular matrix (ECM) are typically derived by processes that involve decellularization of tissues or organs. Preservation of the complex composition and three-dimensional ultrastructure of the ECM is highly desirable but it is recognized that all methods of decellularization result in disruption of the architecture and potential loss of surface structure and composition. Physical methods and chemical and biologic agents are used in combination to lyse cells, followed by rinsing to remove cell remnants. Effective decellularization methodology is dictated by factors such as tissue density and organization, geometric and biologic properties desired for the end product, and the targeted clinical application. Tissue decellularization with preservation of ECM integrity and bioactivity can be optimized by making educated decisions regarding the agents and techniques utilized during processing. An overview of decellularization methods, their effect upon resulting ECM structure and composition, and recently described perfusion techniques for whole organ decellularization techniques are presented herein. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization.

            The extracellular matrix (ECM) is critical for all aspects of vascular biology. In concert with supporting cells, endothelial cells (ECs) assemble a laminin-rich basement membrane matrix that provides structural and organizational stability. During the onset of angiogenesis, this basement membrane matrix is degraded by proteinases, among which membrane-type matrix metalloproteinases (MT-MMPs) are particularly significant. As angiogenesis proceeds, ECM serves essential functions in supporting key signaling events involved in regulating EC migration, invasion, proliferation, and survival. Moreover, the provisional ECM serves as a pliable scaffold wherein mechanical guidance forces are established among distal ECs, thereby providing organizational cues in the absence of cell-cell contact. Finally, through specific integrin-dependent signal transduction pathways, ECM controls the EC cytoskeleton to orchestrate the complex process of vascular morphogenesis by which proliferating ECs organize into multicellular tubes with functional lumens. Thus, the composition of ECM and therefore the regulation of ECM degradation and remodeling serves pivotally in the control of lumen and tube formation and, finally, neovessel stability and maturation.
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              Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart.

              About 3,000 individuals in the United States are awaiting a donor heart; worldwide, 22 million individuals are living with heart failure. A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Generating a bioartificial heart requires engineering of cardiac architecture, appropriate cellular constituents and pump function. We decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent acellular valves and intact chamber geometry. To mimic cardiac cell composition, we reseeded these constructs with cardiac or endothelial cells. To establish function, we maintained eight constructs for up to 28 d by coronary perfusion in a bioreactor that simulated cardiac physiology. By day 4, we observed macroscopic contractions. By day 8, under physiological load and electrical stimulation, constructs could generate pump function (equivalent to about 2% of adult or 25% of 16-week fetal heart function) in a modified working heart preparation.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                08 August 2022
                2022
                : 10
                : 951644
                Affiliations
                [1] 1 Biomedical Engineering and Healthcare Engineering Innovation Center , Khalifa University , Abu Dhabi, United Arab Emirates
                [2] 2 Department of Immunology and Physiology , College of Medicine and Health Sciences , Khalifa University , Abu Dhabi, United Arab Emirates
                [3] 3 Center for Biotechnology , Khalifa University , Abu Dhabi, United Arab Emirates
                Author notes

                Edited by: Kamal Hany Hussein, Assiut University, Egypt

                Reviewed by: Axel Haverich, Hannover Medical School, Germany

                Filippo Naso, Biocompatibility Innovation Srl, Italy

                *Correspondence: Peter R. Corridon, peter.corridon@ 123456ku.ac.ae

                This article was submitted to Biomaterials, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                951644
                10.3389/fbioe.2022.951644
                9394443
                36003539
                0b706a73-8d7f-4e56-bd42-36c1d318d3f4
                Copyright © 2022 Wang, Chan and Corridon.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 May 2022
                : 14 July 2022
                Categories
                Bioengineering and Biotechnology
                Review

                decellularization,recellularization,bioartificial,blood vessel,vascular tissue engineering,vascular replacement therapy

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