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      Bioprinting of three-dimensional dentin–pulp complex with local differentiation of human dental pulp stem cells

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          Abstract

          Numerous approaches have been introduced to regenerate artificial dental tissues. However, conventional approaches are limited when producing a construct with three-dimensional patient-specific shapes and compositions of heterogeneous dental tissue. In this research, bioprinting technology was applied to produce a three-dimensional dentin–pulp complex with patient-specific shapes by inducing localized differentiation of human dental pulp stem cells within a single structure. A fibrin-based bio-ink was designed for bioprinting with the human dental pulp stem cells. The effects of fibrinogen concentration within the bio-ink were investigated in terms of printability, human dental pulp stem cell compatibility, and differentiation. The results show that micro-patterns with human dental pulp stem cells could be achieved with more than 88% viability. Its odontogenic differentiation was also regulated according to the fibrinogen concentration. Based on these results, a dentin–pulp complex having patient-specific shape was produced by co-printing the human dental pulp stem cell–laden bio-inks with polycaprolactone, which is a bio-thermoplastic used for producing the overall shape. After culturing with differentiation medium for 15 days, localized differentiation of human dental pulp stem cells in the outer region of the three-dimensional cellular construct was successfully achieved with localized mineralization. This result demonstrates the possibility to produce patient-specific composite tissues for tooth tissue engineering using three-dimensional bioprinting technology.

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          Most cited references35

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          The development of a bioengineered organ germ method.

          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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            Prevalence of malocclusion and orthodontic treatment need in children and adolescents in Bogota, Colombia. An epidemiological study related to different stages of dental development.

            The aim of the study was to assess the prevalence of malocclusion in a population of Bogotanian children and adolescents in terms of different degrees of severity in relation to sex and specific stages of dental development, in order to evaluate the need for orthodontic treatment in this part of Colombia. A sample of 4724 children (5-17 years of age) was randomly selected from a population that attended the Dental Health Service; none had been orthodontically treated. Based on their dental stages the subjects were grouped into deciduous, early mixed, late mixed and permanent dentition. The registrations were performed according to a method by Björk et al. (1964). The need for orthodontic treatment was evaluated according to an index used by the Swedish National Board of Health. The results showed that 88 per cent of the subjects had some type of anomaly, from mild to severe, half of them recorded as occlusal anomalies, one-third as space discrepancies, and one-fifth as dental anomalies. No clear sex differences were noted, except for maxillary overjet, spacing, tooth size (all more frequent in boys), and crowding (more frequent in girls). Occlusal anomalies and space discrepancies varied in the different dental developmental periods, as did tipped and rotated teeth. Little need for orthodontic treatment was found in 35 per cent and moderate need in 30 per cent. A great need was estimated in 20 per cent, comprising children with prenormal occlusion, maxillary overjet, or overbite (> 6 mm), posterior unilateral crossbite with midline deviation (> 2 mm), severe crowding or spacing, congenitally missing maxillary incisors, impacted maxillary canines or anterior open bite (> 3 mm in the permanent dentition). Urgent need for treatment was estimated to be 3 per cent, comprising subjects with extreme post- and pre-normal occlusion, impacted maxillary incisors or extensive aplasia.
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              Human dental pulp stem cells: Applications in future regenerative medicine.

              Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine.
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                Author and article information

                Journal
                J Tissue Eng
                J Tissue Eng
                TEJ
                sptej
                Journal of Tissue Engineering
                SAGE Publications (Sage UK: London, England )
                2041-7314
                19 May 2019
                Jan-Dec 2019
                : 10
                : 2041731419845849
                Affiliations
                [1 ]Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea
                [2 ]Department of Oral Biochemistry, School of Dentistry, Pusan National University, Yangsan, South Korea
                [3 ]Institute of Translational Dental Sciences, School of Dentistry, Pusan National University, Yangsan, South Korea
                [4 ]Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, South Korea
                [5 ]College of Dentistry, Dankook University, Cheonan, South Korea
                Author notes
                [*]Hyung-Ryong Kim, Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, South Korea. Email: hrkimdp@ 123456gmail.com
                [*]Hyun-Wook Kang, Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), 50, UNIST-gil, Ulsan 44919, South Korea. Email: hkang@ 123456unist.ac.kr
                Author information
                https://orcid.org/0000-0002-6710-6964
                Article
                10.1177_2041731419845849
                10.1177/2041731419845849
                6535759
                31205671
                fbd1b69b-8e0a-4703-88f7-a8c95bd67d30
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 19 March 2019
                : 2 April 2019
                Funding
                Funded by: Ministry of Science, ICT and Future Planning, FundRef https://doi.org/10.13039/501100003621;
                Award ID: NRF-2017M3A9E4047243
                Categories
                Original Article
                Custom metadata
                January-December 2019

                Biomedical engineering
                bioprinting,stem cells,cell differentiation,dentin,dental pulp,tissue engineering

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