Cell-Derived Extracellular Matrix for Tissue Engineering and Regenerative Medicine

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Abstract

Cell-derived extracellular matrices (CD-ECMs) captured increasing attention since the first studies in the 1980s. The biological resemblance of CD-ECMs to their in vivo counterparts and natural complexity provide them with a prevailing bioactivity. CD-ECMs offer the opportunity to produce microenvironments with costumizable biological and biophysical properties in a controlled setting. As a result, CD-ECMs can improve cellular functions such as stemness or be employed as a platform to study cellular niches in health and disease. Either on their own or integrated with other materials, CD-ECMs can also be utilized as biomaterials to engineer tissues de novo or facilitate endogenous healing and regeneration. This review provides a brief overview over the methodologies used to facilitate CD-ECM deposition and manufacturing. It explores the versatile uses of CD-ECM in fundamental research and therapeutic approaches, while highlighting innovative strategies. Furthermore, current challenges are identified and it is accentuated that advancements in methodologies, as well as innovative interdisciplinary approaches are needed to take CD-ECM-based research to the next level.

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Most cited references 116

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An overview of tissue and whole organ decellularization processes.

Peter M Crapo, Thomas W Gilbert, Stephen F Badylak (2011)

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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Extracellular matrix structure.

Achilleas Theocharis, Spyros Skandalis, Chrysostomi Gialeli … (2016)

Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented.

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Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization.

George Davis, Donald Senger (2005)

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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Author and article information

Contributors

Marisa Assunção: URI : http://loop.frontiersin.org/people/1083954/overview

Dorsa Dehghan-Baniani: URI : http://loop.frontiersin.org/people/1146991/overview

Chi Him Kendrick Yiu: URI : http://loop.frontiersin.org/people/1076630/overview

Thomas Später: URI : http://loop.frontiersin.org/people/1036786/overview

Sebastian Beyer: URI : http://loop.frontiersin.org/people/938015/overview

Anna Blocki: URI : http://loop.frontiersin.org/people/1076529/overview

Journal

Journal ID (nlm-ta): Front Bioeng Biotechnol

Journal ID (iso-abbrev): Front Bioeng Biotechnol

Journal ID (publisher-id): Front. Bioeng. Biotechnol.

Title: Frontiers in Bioengineering and Biotechnology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2296-4185

Publication date (Electronic): 03 December 2020

Publication date Collection: 2020

Volume: 8

Electronic Location Identifier: 602009

Affiliations

[1] ¹School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong , Shatin, Hong Kong

[2] ²Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong , Shatin, Hong Kong

[3] ³Institute for Clinical and Experimental Surgery, University of Saarland , Saarbrücken, Germany

[4] ⁴Department of Biomedical Engineering, Faculty of Engineering, The Chinese University of Hong Kong , Shatin, Hong Kong

[5] ⁵Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong , Shatin, Hong Kong

Author notes

Edited by: Xin Zhao, Hong Kong Polytechnic University, Hong Kong

Reviewed by: Masoud Mozafari, University of Toronto, Canada; Katiucia Batista Silva Paiva, University of São Paulo, Brazil

*Correspondence: Anna Blocki, anna.blocki@ 123456cuhk.edu.hk

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

Article

DOI: 10.3389/fbioe.2020.602009

PMC ID: 7744374

PubMed ID: 33344434

SO-VID: 456dc8c9-d0b5-4d4a-b5ac-4f5e56994668

License:

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

Date received : 02 September 2020

Date accepted : 10 November 2020

Page count

Figures: 2, Tables: 0, Equations: 0, References: 116, Pages: 10, Words: 0

Funding

Funded by: Innovation and Technology Commission - Hong Kong 10.13039/501100007156

Cell-Derived Extracellular Matrix for Tissue Engineering and Regenerative Medicine

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Abstract

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Most cited references 116

An overview of tissue and whole organ decellularization processes.

Extracellular matrix structure.

Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization.

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