Tissue-Specific Decellularization Methods: Rationale and Strategies to Achieve Regenerative Compounds

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Abstract

The extracellular matrix (ECM) is a complex network with multiple functions, including specific functions during tissue regeneration. Precisely, the properties of the ECM have been thoroughly used in tissue engineering and regenerative medicine research, aiming to restore the function of damaged or dysfunctional tissues. Tissue decellularization is gaining momentum as a technique to obtain potentially implantable decellularized extracellular matrix (dECM) with well-preserved key components. Interestingly, the tissue-specific dECM is becoming a feasible option to carry out regenerative medicine research, with multiple advantages compared to other approaches. This review provides an overview of the most common methods used to obtain the dECM and summarizes the strategies adopted to decellularize specific tissues, aiming to provide a helpful guide for future research development.

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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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B Chan, K Leong (2008)

Scaffolds represent important components for tissue engineering. However, researchers often encounter an enormous variety of choices when selecting scaffolds for tissue engineering. This paper aims to review the functions of scaffolds and the major scaffolding approaches as important guidelines for selecting scaffolds and discuss the tissue-specific considerations for scaffolding, using intervertebral disc as an example.

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Structure of the tendon connective tissue.

P Kannus (2000)

Tendons consist of collagen (mostly type I collagen) and elastin embedded in a proteoglycan-water matrix with collagen accounting for 65-80% and elastin approximately 1-2% of the dry mass of the tendon. These elements are produced by tenoblasts and tenocytes, which are the elongated fibroblasts and fibrocytes that lie between the collagen fibers, and are organized in a complex hierarchical scheme to form the tendon proper. Soluble tropocollagen molecules form cross-links to create insoluble collagen molecules which then aggregate progressively into microfibrils and then into electronmicroscopically clearly visible units, the collagen fibrils. A bunch of collagen fibrils forms a collagen fiber, which is the basic unit of a tendon. A fine sheath of connective tissue called endotenon invests each collagen fiber and binds fibers together. A bunch of collagen fibers forms a primary fiber bundle, and a group of primary fiber bundles forms a secondary fiber bundle. A group of secondary fiber bundles, in turn, forms a tertiary bundle, and the tertiary bundles make up the tendon. The entire tendon is surrounded by a fine connective tissue sheath called epitenon. The three-dimensional ultrastructure of tendon fibers and fiber bundles is complex. Within one collagen fiber, the fibrils are oriented not only longitudinally but also transversely and horizontally. The longitudinal fibers do not run only parallel but also cross each other, forming spirals. Some of the individual fibrils and fibril groups form spiral-type plaits. The basic function of the tendon is to transmit the force created by the muscle to the bone, and, in this way, make joint movement possible. The complex macro- and microstructure of tendons and tendon fibers make this possible. During various phases of movements, the tendons are exposed not only to longitudinal but also to transversal and rotational forces. In addition, they must be prepared to withstand direct contusions and pressures. The above-described three-dimensional internal structure of the fibers forms a buffer medium against forces of various directions, thus preventing damage and disconnection of the fibers.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 30 July 2020

Publication date Collection: August 2020

Volume: 21

Issue: 15

Electronic Location Identifier: 5447

Affiliations

[1 ]Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia-San Sebastian, Spain; umendibil@ 123456cicbiomagune.es (U.M.); rruiz@ 123456cicbiomagune.es (R.R.-H.); sretegi@ 123456cicbiomagune.es (S.R.-C.)

[2 ]TECNALIA, Basque Research and Technology Alliance (BRTA), 20009 Donostia-San Sebastian, Spain; nerea.garcia@ 123456tecnalia.com (N.G.-U.); beatriz.olalde@ 123456tecnalia.com (B.O.-G.)

[3 ]Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain

Author notes

[* ]Correspondence: aabarrategi@ 123456cicbiomagune.es

[†]

These authors contribute equally to the work.

Author information

Raquel Ruiz-Hernandez https://orcid.org/0000-0001-6166-380X

Sugoi Retegi-Carrion https://orcid.org/0000-0002-0320-133X

Beatriz Olalde-Graells https://orcid.org/0000-0003-4523-0849

Ander Abarrategi https://orcid.org/0000-0002-6510-2337

Article

Publisher ID: ijms-21-05447

DOI: 10.3390/ijms21155447

PMC ID: 7432490

PubMed ID: 32751654

SO-VID: aaaefd58-4ebb-477a-ba2c-3adb1ff5d18f

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Tissue-Specific Decellularization Methods: Rationale and Strategies to Achieve Regenerative Compounds

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Abstract

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Entomologia Generalis

Most cited references 158

An overview of tissue and whole organ decellularization processes.

Scaffolding in tissue engineering: general approaches and tissue-specific considerations.

Structure of the tendon connective tissue.

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