Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy
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{"title"=>"Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy", "type"=>"journal", "authors"=>[{"first_name"=>"Masamitsu", "last_name"=>"Oshima", "scopus_author_id"=>"45061246900"}, {"first_name"=>"Mitsumasa", "last_name"=>"Mizuno", "scopus_author_id"=>"35726003400"}, {"first_name"=>"Aya", "last_name"=>"Imamura", "scopus_author_id"=>"45061047800"}, {"first_name"=>"Miho", "last_name"=>"Ogawa", "scopus_author_id"=>"16028757000"}, {"first_name"=>"Masato", "last_name"=>"Yasukawa", "scopus_author_id"=>"45061141900"}, {"first_name"=>"Hiromichi", "last_name"=>"Yamazaki", "scopus_author_id"=>"45061152200"}, {"first_name"=>"Ritsuko", "last_name"=>"Morita", "scopus_author_id"=>"16028992100"}, {"first_name"=>"Etsuko", "last_name"=>"Ikeda", "scopus_author_id"=>"23397538900"}, {"first_name"=>"Kazuhisa", "last_name"=>"Nakao", "scopus_author_id"=>"16022622600"}, {"first_name"=>"Teruko", "last_name"=>"Takano-Yamamoto", "scopus_author_id"=>"55666401900"}, {"first_name"=>"Shohei", "last_name"=>"Kasugai", "scopus_author_id"=>"16181183100"}, {"first_name"=>"Masahiro", "last_name"=>"Saito", "scopus_author_id"=>"55727980600"}, {"first_name"=>"Takashi", "last_name"=>"Tsuji", "scopus_author_id"=>"35403158700"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"21765896", "doi"=>"10.1371/journal.pone.0021531", "sgr"=>"79960184179", "isbn"=>"1932-6203", "scopus"=>"2-s2.0-79960184179", "issn"=>"19326203", "pui"=>"362118218"}, "id"=>"2150cc8a-8135-35db-a5fd-588e50e615b1", "abstract"=>"Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy.", "link"=>"http://www.mendeley.com/research/functional-tooth-regeneration-using-bioengineered-tooth-unit-mature-organ-replacement-regenerative-t", "reader_count"=>151, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>8, "Researcher"=>24, "Student > Doctoral Student"=>10, "Student > Ph. D. Student"=>27, "Student > Postgraduate"=>14, "Student > Master"=>24, "Other"=>11, "Student > Bachelor"=>19, "Lecturer"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>8, "Researcher"=>24, "Student > Doctoral Student"=>10, "Student > Ph. D. Student"=>27, "Student > Postgraduate"=>14, "Student > Master"=>24, "Other"=>11, "Student > Bachelor"=>19, "Lecturer"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Engineering"=>11, "Unspecified"=>9, "Biochemistry, Genetics and Molecular Biology"=>10, "Materials Science"=>4, "Agricultural and Biological Sciences"=>50, "Medicine and Dentistry"=>58, "Arts and Humanities"=>1, "Business, Management and Accounting"=>1, "Physics and Astronomy"=>2, "Chemistry"=>1, "Social Sciences"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>11}, "Materials Science"=>{"Materials Science"=>4}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>58}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>50}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>10}, "Unspecified"=>{"Unspecified"=>9}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Sweden"=>1, "United States"=>1, "Japan"=>1, "Mexico"=>1, "France"=>1, "Peru"=>1, "Portugal"=>1, "Switzerland"=>1, "India"=>1}, "group_count"=>5}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/757909"], "description"=>"<p>(A) Schematic representation of a murine extensive bone defect model and the transplantation of a bioengineered tooth unit (arrowhead). (B) Micro-CT images of the vertical alveolar bone regeneration processes in a no transplantation control (<i>upper</i>) and following the transplantation of a bioengineered tooth unit (arrowhead, <i>lower</i>) in a murine extensive bone defect model. Vertical bone formation was observed from the marginal bone of the recipient (arrow). Scale bar, 500 µm. (C) Three-dimensional superposition of micro-CT images of natural dentition (gray, double dotted line), a transplanted bioengineered tooth unit (<i>lower</i>) and a no transplantation control (<i>upper</i>) at day 0 in an extensive bone defect (red, straight line), and at 45 days after transplantation (green, dotted line). The superior edges of the recipient alveolar bone are indicated by each line. (D) Regenerative bone volume of the buccal area following the transplantation of a bioengineered tooth unit (transplant) and no transplantation (control) at day 45 in an extensive bone defect. Error bars show the standard deviation (<i>n</i> = 4). *<i>P</i><0.01 (<i>t</i>-test).</p>", "links"=>[], "tags"=>["regeneration", "transplantation", "bioengineered"], "article_id"=>428264, "categories"=>["Medicine", "Biotechnology", "Developmental Biology"], "users"=>["Masamitsu Oshima", "Mitsumasa Mizuno", "Aya Imamura", "Miho Ogawa", "Masato Yasukawa", "Hiromichi Yamazaki", "Ritsuko Morita", "Etsuko Ikeda", "Kazuhisa Nakao", "Teruko Takano-Yamamoto", "Shohei Kasugai", "Masahiro Saito", "Takashi Tsuji"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021531.g004", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alveolar_bone_regeneration_following_the_transplantation_of_a_bioengineered_tooth_unit_/428264", "title"=>"Alveolar bone regeneration following the transplantation of a bioengineered tooth unit.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-12 02:17:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/757716"], "description"=>"<p>(A) Sections of natural and bioengineered teeth were analyzed by TRAP-staining and <i>in situ</i> hybridization analysis of <i>Ocn</i> mRNA at day 6 of orthodontic treatment. TRAP-positive cells (arrow) and <i>Ocn</i> mRNA-positive cells (arrowhead) are indicated. Scale bar, 100 µm. (B) Nerve fibers and blood vessels in the pulp and PDL of a natural tooth (<i>top</i>), a bioengineered tooth unit in an SRC (<i>middle</i>), and a bioengineered tooth at 40 days after transplantation (<i>bottom</i>) were analyzed immunohistochemically using specific antibodies for neurofilament (NF; green) and von Willebrand Factor (vWF; red). Scale bar, 50 µm. D, dentin; P, pulp; AB, alveolar bone; PDL, periodontal ligament. (C) Analysis of c-Fos immunoreactive neurons in the medullary dorsal horns of mice after 0 hours (no stimulation, control; <i>top</i>), 2 hours of stimulation by orthodontic force (<i>middle</i>) and pulp exposure (<i>bottom</i>). C-Fos (arrowhead) was detectable after these stimulations in both natural (<i>left</i>) and bioengineered teeth at 40 days post-transplantation (<i>right</i>). Scale bar, 100 µm. T, spinal trigeminal tract.</p>", "links"=>[], "tags"=>["surgery", "biotechnology", "developmental biology"], "article_id"=>428076, "categories"=>["Medicine", "Biotechnology", "Developmental Biology"], "users"=>["Masamitsu Oshima", "Mitsumasa Mizuno", "Aya Imamura", "Miho Ogawa", "Masato Yasukawa", "Hiromichi Yamazaki", "Ritsuko Morita", "Etsuko Ikeda", "Kazuhisa Nakao", "Teruko Takano-Yamamoto", "Shohei Kasugai", "Masahiro Saito", "Takashi Tsuji"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021531.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experimental_tooth_movement_and_pain_response_to_mechanical_stress_/428076", "title"=>"Experimental tooth movement and pain response to mechanical stress.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-12 02:14:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/381125", "https://ndownloader.figshare.com/files/381131", "https://ndownloader.figshare.com/files/381147", "https://ndownloader.figshare.com/files/381163"], "description"=>"<div><p>Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging <em>in vivo</em>. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy.</p> </div>", "links"=>[], "tags"=>["regeneration", "bioengineered", "mature", "regenerative"], "article_id"=>135285, "categories"=>["Medicine", "Biotechnology", "Developmental Biology"], "users"=>["Masamitsu Oshima", "Mitsumasa Mizuno", "Aya Imamura", "Miho Ogawa", "Masato Yasukawa", "Hiromichi Yamazaki", "Ritsuko Morita", "Etsuko Ikeda", "Kazuhisa Nakao", "Teruko Takano-Yamamoto", "Shohei Kasugai", "Masahiro Saito", "Takashi Tsuji"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0021531.s001", "https://dx.doi.org/10.1371/journal.pone.0021531.s002", "https://dx.doi.org/10.1371/journal.pone.0021531.s003", "https://dx.doi.org/10.1371/journal.pone.0021531.s004"], "stats"=>{"downloads"=>5, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Functional_Tooth_Regeneration_Using_a_Bioengineered_Tooth_Unit_as_a_Mature_Organ_Replacement_Regenerative_Therapy/135285", "title"=>"Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-07-12 01:28:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/757551"], "description"=>"<p>(A) Schematic representation of the protocol used to transplant a bioengineered tooth unit in a murine tooth loss model. (B) Photograph (<i>Upper</i>) and sectional image (<i>Lower</i>) of a calcein-labeled bioengineered tooth unit at 60 days post transplantation in an SRC. Scale bar, 200 µm. (C) Micro-CT images of a bioengineered tooth unit (arrowhead) in cross section (<i>upper</i>) and frontal section (<i>first and second figures from the lower left</i>) during the processes of bone remodeling and connection between the recipient jaw bone and alveolar bone of the tooth unit. Histological analysis of the engrafted bioengineered tooth unit at 40 days post transplantation was also performed. (Scale bar, 500 µm and 100 µm in the lower and higher magnification figure; <i>third and fourth figure from the lower left</i>). NT, natural tooth; BT, bioengineered tooth; AB, alveolar bone; PDL, periodontal ligament. (D) Sectional images of a calcein-labeled bioengineered tooth unit at 14, 30 and 40 days post-transplantation. The calcein-labeled bone of the bioengineered tooth units (arrowhead) was found to gradually decrease from the outside and finally disappear at 40 days post-transplantation. Scale bar, 500 µm (<i>upper</i>), 50 µm (<i>lower</i>). NT, natural tooth; BT, bioengineered tooth. (E) Oral photographs (<i>upper</i>) and micro-CT (<i>lower</i>) images showing occlusion of natural (<i>left</i>) and bioengineered teeth (<i>right</i>). Scale bar, 500 µm. (F) Assessment of the hardness of a bioengineered tooth. Knoop microhardness values of the enamel (<i>upper</i>) and dentin (<i>lower</i>) of a bioengineered tooth at 60 days post-transplantation in a subrenal capsule (SRC) and at 40 days post-transplantation in jawbone (TP) were compared with those of natural teeth in 11-week-old mice. Error bars show the standard deviation (<i>n</i> = 5). *<i>P</i><0.01 (<i>t</i>-test).</p>", "links"=>[], "tags"=>["occlusion", "bioengineered"], "article_id"=>427910, "categories"=>["Medicine", "Biotechnology", "Developmental Biology"], "users"=>["Masamitsu Oshima", "Mitsumasa Mizuno", "Aya Imamura", "Miho Ogawa", "Masato Yasukawa", "Hiromichi Yamazaki", "Ritsuko Morita", "Etsuko Ikeda", "Kazuhisa Nakao", "Teruko Takano-Yamamoto", "Shohei Kasugai", "Masahiro Saito", "Takashi Tsuji"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021531.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Engraftment_and_occlusion_of_a_bioengineered_tooth_unit_in_a_tooth_loss_model_/427910", "title"=>"Engraftment and occlusion of a bioengineered tooth unit in a tooth loss model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-12 02:11:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/757405"], "description"=>"<p>(A) Schematic representation of the generative technology of bioengineered tooth unit. (B) Phase construct imagery of a bioengineered tooth germ on day 1 (<i>left</i>) and 5 (<i>center</i>) and HE staining (<i>right</i>) of an organ culture on day 5. Scale bar, 200 µm. E, epithelium; M, mesenchyme. (C) Photographs (<i>upper</i>) and micro-CT images of the external surface area (<i>middle</i>) and cross section (<i>lower</i>) of a bioengineered tooth unit. Images were captured at 20 days (<i>left</i>), 30 days (<i>center</i>) and 60 days (<i>right</i>) after subrenal capsule transplantation (SRC). Scale bar, 200 µm. C, tooth crown side; R, tooth root side. (D) Histological analysis of the bioengineered tooth unit on day 30 after SRC transplantation (<i>left</i>). (Scale bar, 500 µm). Higher magnification images of crown area (<i>upper right</i>) and the periodontal tissue area (<i>lower right</i>) are also shown. Scale bar, 50 µm. E, enamel; D, dentin; AB, alveolar bone; PDL, periodontal ligament. (E) Photographs of the developmental processes occurring in bioengineered tooth germ in a subrenal capsule (SRC) using a size-control device. Images were captured of bioengineered tooth germ orientated in the device (<i>top left</i>), transplantation into the SRC (<i>top right</i>), and the bioengineered tooth at 50–60 days after transplantation in the SRC (middle). Micro-CT images of the external surface area (<i>bottom left</i>) and cross section (<i>bottom left</i>) are also show. The dotted lines indicate the outlines of the device. Scale bar, 500 µm. (F) Micro-CT images of a bioengineered tooth unit transplanted into the SRC for 30 days with (<i>lower column</i>) or without (<i>upper column</i>) the size-control device at an external (<i>left</i>), axial (<i>center</i>) or cross section (<i>right</i>) view. Scale bar, 500 µm. x, x-axis of the crown; y, y-axis of the crown. (G) X-axis versus y-axis ratios (x/y) of the crowns of bioengineered tooth units at 30 days post transplantation into an SRC, and also of natural first, second and third molars from 9-week-old mice. Transplantations were performed with or without the 1.3 mm thickness size-control device. Error bars show the standard deviation (<i>n</i> = 5). *<i>P</i><0.001 (<i>t</i>-test). (H) The lengths of the bioengineered tooth units generated using size-control devices, which were of a 1.3 mm (φ1.3 mm) or 1.8 mm (φ1.8 mm) inner diameter, at 30 and 60 days post transplantation into an SRC were compared with or without the devices. Error bars show the standard deviation (<i>n</i> = 5). *<i>P</i><0.01 and **<i>P</i><0.001 (<i>t</i>-test). (I) Photograph (<i>first figure from the left</i>) and micro-CT images showing external (<i>second figure</i>), axial (<i>third figure</i>) and cross section (<i>fourth figure</i>) views of a multiple bioengineered tooth units, in which four teeth were contained in one alveolar bone, after 60 days transplantation into the SRC. Scale bar, 500 µm.</p>", "links"=>[], "tags"=>["bioengineered"], "article_id"=>427759, "categories"=>["Medicine", "Biotechnology", "Developmental Biology"], "users"=>["Masamitsu Oshima", "Mitsumasa Mizuno", "Aya Imamura", "Miho Ogawa", "Masato Yasukawa", "Hiromichi Yamazaki", "Ritsuko Morita", "Etsuko Ikeda", "Kazuhisa Nakao", "Teruko Takano-Yamamoto", "Shohei Kasugai", "Masahiro Saito", "Takashi Tsuji"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021531.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_a_bioengineered_tooth_unit_/427759", "title"=>"Generation of a bioengineered tooth unit.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-12 02:09:19"}

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Relative Metric

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