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      Decellularization in Tissue Engineering and Regenerative Medicine: Evaluation, Modification, and Application Methods

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          Abstract

          Reproduction of different tissues using scaffolds and materials is a major element in regenerative medicine. The regeneration of whole organs with decellularized extracellular matrix (dECM) has remained a goal despite the use of these materials for different purposes. Recently, decellularization techniques have been widely used in producing scaffolds that are appropriate for regenerating damaged organs and may be able to overcome the shortage of donor organs. Decellularized ECM offers several advantages over synthetic compounds, including the preserved natural microenvironment features. Different decellularization methods have been developed, each of which is appropriate for removing cells from specific tissues under certain conditions. A variety of methods have been advanced for evaluating the decellularization process in terms of cell removal efficiency, tissue ultrastructure preservation, toxicity, biocompatibility, biodegradability, and mechanical resistance in order to enhance the efficacy of decellularization methods. Modification techniques improve the characteristics of decellularized scaffolds, making them available for the regeneration of damaged tissues. Moreover, modification of scaffolds makes them appropriate options for drug delivery, disease modeling, and improving stem cells growth and proliferation. However, considering different challenges in the way of decellularization methods and application of decellularized scaffolds, this field is constantly developing and progressively moving forward. This review has outlined recent decellularization and sterilization strategies, evaluation tests for efficient decellularization, materials processing, application, and challenges and future outlooks of decellularization in regenerative medicine and tissue engineering.

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          Most cited references216

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          Matrix elasticity directs stem cell lineage specification.

          Microenvironments appear important in stem cell lineage specification but can be difficult to adequately characterize or control with soft tissues. Naive mesenchymal stem cells (MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. Soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. During the initial week in culture, reprogramming of these lineages is possible with addition of soluble induction factors, but after several weeks in culture, the cells commit to the lineage specified by matrix elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types. Inhibition of nonmuscle myosin II blocks all elasticity-directed lineage specification-without strongly perturbing many other aspects of cell function and shape. The results have significant implications for understanding physical effects of the in vivo microenvironment and also for therapeutic uses of stem cells.
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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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              The extracellular matrix at a glance.

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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
                25 April 2022
                2022
                : 10
                : 805299
                Affiliations
                [1] 1 Pediatric Urology and Regenerative Medicine Research Center , Children’s Medical Center , Pediatric Center of Excellence , Tehran University of Medical Science , Tehran, Iran
                [2] 2 Students’ Scientific Research Center , Tehran University of Medical Sciences , Tehran, Iran
                [3] 3 Department of Physiology , Faculty of Medicine , Tabriz Medical Sciences, Islamic Azad University , Tabriz, Iran
                Author notes

                Edited by: Kamal Hany Hussein, Assiut University, Egypt

                Reviewed by: Renata Kelly Da Palma, Universidad Francisco de Vitoria, Spain

                Chiara Magliaro, University of Pisa, Italy

                Xiaojun Yu, Stevens Institute of Technology, United States

                *Correspondence: Masoumeh Majidi Zolbin, Masoumeh.majidizolbin@ 123456gmail.com ; Abdol-Mohammad Kajbafzadeh, kajbafzd@ 123456tums.ac.ir
                [ † ]

                These authors share first authorship

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

                Article
                805299
                10.3389/fbioe.2022.805299
                9081537
                35547166
                8d43fd03-9fd3-456e-b14c-bb5905d0db85
                Copyright © 2022 Neishabouri, Soltani Khaboushan, Daghigh, Kajbafzadeh and Majidi Zolbin.

                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
                : 30 October 2021
                : 04 April 2022
                Categories
                Bioengineering and Biotechnology
                Review

                extracellular matrix,recellularization,regenerative medicine,decellularizalion,tissue engineering

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