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      Decellularized human periodontal ligament for periodontium regeneration

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          Abstract

          Regenerating the periodontal ligament (PDL) is a crucial factor for periodontal tissue regeneration in the presence of traumatized and periodontally damaged teeth. Various methods have been applied for periodontal regeneration, including tissue substitutes, bioactive materials, and synthetic scaffolds. However, all of these treatments have had limited success in structural and functional periodontal tissue regeneration. To achieve the goal of complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized scaffolds fabricated via tissue engineering. The aim of this study was to fabricate a decellularized periodontal scaffold of human tooth slices and determine its regeneration potential. We evaluated two different protocols applied to tooth slices obtained from human healthy third molars. The extracellular matrix scaffold decellularized using sodium dodecyl sulfate and Triton X-100, which are effective in removing nuclear components, was demonstrated to preserve an intact structure and composition. Furthermore, the decellularized scaffold could support repopulation of PDL stem cells near the cementum and expressed cementum and periodontal-ligament-related genes. These results show that decellularized PDL scaffolds of human teeth are capable of inducing the proliferation and differentiation of mesenchymal stem cells, thus having regeneration potential for use in future periodontal regenerative tissue engineering.

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          Most cited references31

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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.
          Article 0 comments Cited 988 times – based on 0 reviews     Review now
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            Decellularization of tissues and organs.

            Thomas Gilbert, Tiffany Sellaro, Stephen Badylak (2006)
            Decellularized tissues and organs have been successfully used in a variety of tissue engineering/regenerative medicine applications, and the decellularization methods used vary as widely as the tissues and organs of interest. The efficiency of cell removal from a tissue is dependent on the origin of the tissue and the specific physical, chemical, and enzymatic methods that are used. Each of these treatments affect the biochemical composition, tissue ultrastructure, and mechanical behavior of the remaining extracellular matrix (ECM) scaffold, which in turn, affect the host response to the material. Herein, the most commonly used decellularization methods are described, and consideration give to the effects of these methods upon the biologic scaffold material.
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              Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds.

              Stephen F Badylak, Doris Taylor, Korkut Uygun (2011)
              The definitive treatment for end-stage organ failure is orthotopic transplantation. However, the demand for transplantation far exceeds the number of available donor organs. A promising tissue-engineering/regenerative-medicine approach for functional organ replacement has emerged in recent years. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. However, significant challenges for three-dimensional organ engineering approach remain. This manuscript describes the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding bioreactor design to support this approach. Critical challenges and future directions are also discussed.
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                Author and article information

                Contributors
                Hyoju Son: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Mijeong Jeon: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Hyung-Jun Choi: Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Hyo-Seol Lee: Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Ik-Hwan Kim: Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Chung-Min Kang: Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Je Seon Song:
                ORCID: http://orcid.org/0000-0001-8620-5629
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Gianpaolo Papaccio: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 15 August 2019
                Publication date Collection: 2019
                Volume: 14
                Issue: 8
                Electronic Location Identifier: e0221236
                Affiliations
                [1 ] Department of Pediatric Dentistry, College of Dentistry, Yonsei University, Seoul, Republic of Korea
                [2 ] Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Republic of Korea
                [3 ] Department of Pediatric Dentistry, College of Dentistry, Kyunghee University, Seoul, Republic of Korea
                Università degli Studi della Campania, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-8620-5629
                Article
                Publisher ID: PONE-D-19-13453
                DOI: 10.1371/journal.pone.0221236
                PMC ID: 6695143
                PubMed ID: 31415652
                SO-VID: e7389d6d-90db-4e86-bac7-e3665483f29f
                Copyright © © 2019 Son et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 12 May 2019
                Date accepted : 1 August 2019
                Page count
                Figures: 4, Tables: 2, Pages: 12
                Funding
                Funded by: National Research Foundation of Korea (NRF) funded by the Ministry of Education
                Award ID: NRF-2018R1D1A1B07041657
                Award Recipient :
                ORCID: http://orcid.org/0000-0001-8620-5629
                Funded by: National Research Foundation of Korea (NRF) funded by the Ministry of Education
                Award ID: NRF-2018R1D1A1B07046163
                Award Recipient :
                This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education ( https://ernd.nrf.re.kr/index.do) grant NRF-2018R1D1A1B07041657 to JSS and grant NRF-2018R1D1A1B07046163 to HJC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Digestive System
                Subject: Teeth
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Digestive System
                Subject: Teeth
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Head
                Subject: Jaw
                Subject: Teeth
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Head
                Subject: Jaw
                Subject: Teeth
                Subject: Biology and Life Sciences
                Subject: Developmental Biology
                Subject: Morphogenesis
                Subject: Regeneration
                Subject: Tooth Regeneration
                Subject: Biology and Life Sciences
                Subject: Developmental Biology
                Subject: Organism Development
                Subject: Regeneration
                Subject: Tooth Regeneration
                Subject: Biology and Life Sciences
                Subject: Molecular Biology
                Subject: Molecular Biology Techniques
                Subject: Artificial Gene Amplification and Extension
                Subject: Polymerase Chain Reaction
                Subject: Research and Analysis Methods
                Subject: Molecular Biology Techniques
                Subject: Artificial Gene Amplification and Extension
                Subject: Polymerase Chain Reaction
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Stem Cells
                Subject: Biology and Life Sciences
                Subject: Developmental Biology
                Subject: Cell Differentiation
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Proteins
                Subject: Collagens
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Digestive Physiology
                Subject: Dentition
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Digestive Physiology
                Subject: Dentition
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Stem Cells
                Subject: Mesenchymal Stem Cells
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                Data Availability All relevant data are within the manuscript.

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