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      Tooth Formation: Are the Hardest Tissues of Human Body Hard to Regenerate?

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          Abstract

          With increasing life expectancy, demands for dental tissue and whole-tooth regeneration are becoming more significant. Despite great progress in medicine, including regenerative therapies, the complex structure of dental tissues introduces several challenges to the field of regenerative dentistry. Interdisciplinary efforts from cellular biologists, material scientists, and clinical odontologists are being made to establish strategies and find the solutions for dental tissue regeneration and/or whole-tooth regeneration. In recent years, many significant discoveries were done regarding signaling pathways and factors shaping calcified tissue genesis, including those of tooth. Novel biocompatible scaffolds and polymer-based drug release systems are under development and may soon result in clinically applicable biomaterials with the potential to modulate signaling cascades involved in dental tissue genesis and regeneration. Approaches for whole-tooth regeneration utilizing adult stem cells, induced pluripotent stem cells, or tooth germ cells transplantation are emerging as promising alternatives to overcome existing in vitro tissue generation hurdles. In this interdisciplinary review, most recent advances in cellular signaling guiding dental tissue genesis, novel functionalized scaffolds and drug release material, various odontogenic cell sources, and methods for tooth regeneration are discussed thus providing a multi-faceted, up-to-date, and illustrative overview on the tooth regeneration matter, alongside hints for future directions in the challenging field of regenerative dentistry.

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          Designing hydrogels for controlled drug delivery

          David Mooney, Jianyu Li (2016)
          Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
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            The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems--a review.

            Susanne Fredenberg, Marie Wahlgren, Mats Reslow … (2011)
            Poly(D,L-lactic-co-glycolic acid) (PLGA) is the most frequently used biodegradable polymer in the controlled release of encapsulated drugs. Understanding the release mechanisms, as well as which factors that affect drug release, is important in order to be able to modify drug release. Drug release from PLGA-based drug delivery systems is however complex. This review focuses on release mechanisms, and provides a survey and analysis of the processes determining the release rate, which may be helpful in elucidating this complex picture. The term release mechanism and the various techniques that have been used to study release mechanisms are discussed. The physico-chemical processes that influence the rate of drug release and the various mechanisms of drug release that have been reported in the literature are analyzed in this review, and practical examples are given. The complexity of drug release from PLGA-based drug delivery systems can make the generalization of results and predictions of drug release difficult. However, this complexity also provides many possible ways of solving problems and modifying drug release. Basic, generally applicable and mechanistic research provides pieces of the puzzle, which is useful in the development of controlled-release pharmaceuticals. Copyright © 2011 Elsevier B.V. All rights reserved.
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              The development of a bioengineered organ germ method.

              Kazuhisa Nakao, Ritsuko Morita, Yasumitsu Saji … (2007)
              To bioengineer ectodermal organs such as teeth and whisker follicles, we developed a three-dimensional organ-germ culture method. The bioengineered tooth germ generated a structurally correct tooth, after both in vitro organ culture as well as transplantation under a tooth cavity in vivo, showing penetration of blood vessels and nerve fibers. Our method provides a substantial advance in the development of bioengineered organ replacement strategies and regenerative therapies.
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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): 04 June 2020
                Publication date Collection: June 2020
                Volume: 21
                Issue: 11
                Electronic Location Identifier: 4031
                Affiliations
                [1 ]Department of Biochemistry, Institute of Chemistry, University of São Paulo, Avenida Professor Lineu Prestes 748, Vila Universitária, São Paulo 05508-000, Brazil; jbaranova@ 123456usp.br
                [2 ]Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Straße 20, 53359 Rheinbach, NRW, Germany; dominik.buechner@ 123456h-brs.de (D.B.); margit.schulze@ 123456h-brs.de (M.S.)
                [3 ]Oral Biology Laboratory, Department of Orthodontics, Dental Hospital of the University of Bonn, Welschnonnenstraße 17, 53111 Bonn, NRW, Germany; wgoetz@ 123456uni-bonn.de
                Author notes
                [* ]Correspondence: edda.tobiasch@ 123456h-brs.de ; Tel.: +49-2241-865-576
                Author information
                https://orcid.org/0000-0002-8975-1753
                Article
                Publisher ID: ijms-21-04031
                DOI: 10.3390/ijms21114031
                PMC ID: 7312198
                PubMed ID: 32512908
                SO-VID: ea01a6bc-c306-4db0-bc43-4d20d0babc7a
                Copyright © © 2020 by the authors.
                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/).

                History
                Date received : 29 April 2020
                Date accepted : 03 June 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: dentogenesis,amelogenesis,dentinogenesis,cementogenesis,drug release materials,scaffolds,odontogenic cells,stem cells,whole-tooth regeneration
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: dentogenesis, amelogenesis, dentinogenesis, cementogenesis, drug release materials, scaffolds, odontogenic cells, stem cells, whole-tooth regeneration

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