Essence of diagnosis and management of sleep bruxism


Identification of microRNA signatures in peripheral blood of young women as potential biomarkers for metal allergy

MicroRNA (miRNA) is a short (19-24 nucleotide) endogenous non-protein RNA that exists in the body and controls the translation process from genes to proteins. It has become useful as a diagnostic tool and a potential treatment target in cancer research. To explore the function of miRNA in contact dermatitis, female participants with a positive metal allergy diagnosis ( = 3) were enrolled along with additional female participants with no medical history of metal allergy ( = 3). A patch test was performed on each participant. Peripheral blood was collected from all the participants before the patch test and at days 3 and 7 after starting the patch test. After total RNA was obtained from peripheral blood leukocytes and cDNA was generated, microarray analysis was performed to analyze the large-scale circulating miRNA profile. Real-time polymerase chain reaction (RT-PCR) was then used to clarify the overall target miRNA expression. Downregulation of hsa-let-7d-5p, hsa-miR-24-3p, hsa-miR-23b-3p, hsa-miR-26b-5p, and hsa-miR-150-5p was found on day 7. Certain miRNAs were confirmed using RT-PCR. These peripheral blood miRNAs could be diagnostic biomarkers for metal allergies.


Analgesic effect of tranilast in an animal model of neuropathic pain and its role in the regulation of tetrahydrobiopterin synthesis

International Journal of Molecular Sciences


Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model


A case of fixed prosthodontic treatment through tooth preservation with occlusal traumatic symptoms

咬合性外傷による重度動揺歯に対して歯の保存を行い固定性補綴装置にて機能回復を行った症例

Patient: A 64-year-old female patient complained of masticatory dysfunction caused by mobility of a maxillary right fixed bridge. The maxillary right canine with occlusal traumatic symptoms had been diagnosed by her previous dentist as indicated for extraction, but it was fixed with a provisional bridge to determine whether the tooth could recover. After this traumatic tooth was allowed to recover, the fabricated fixed bridge was finally attached after a follow-up observation by temporary cementation.

Discussion: There are no clear criteria for tooth preservation of occlusal traumatic teeth depending on bone resorption or tooth mobility. Therefore, it is important to plan a step-by-step prosthodontic treatment in which the availability of abutment teeth is determined after the acute traumatic symptoms have resolved.

Conclusion: A careful and step-by-step prosthodontic treatment for an occlusal traumatic tooth resulted in tooth preservation, restoration of masticatory function, and improvement of patient satisfaction.

症例の概要:患者は64歳女性．上顎右側ブリッジの動揺による咀嚼困難を主訴に来院した．咬合性外傷症状が認められた上顎右側犬歯に対して，暫間補綴装置による固定と咬合力の分散にて症状改善を図り，製作した固定性補綴装置を仮着して経過観察を行った後に装着した．

考察:咬合性外傷を有する歯の保存可否を判断するためには，適切な原因除去と急性症状の消退が得られたのちに，支台歯として利用が可能かを見極める段階的な補綴治療計画が重要であると考えられた．

結論:他院にて抜歯適応と診断された歯の保存可否を適切に判断した後に，固定性補綴装置を装着することにより，支台歯への利用と咀嚼機能の回復，患者満足度の改善に貢献できた．


Dentin-pulp complex tissue regeneration via three-dimensional cell sheet layering

The dentin-pulp complex is a unique structure in teeth that contains both hard and soft tissues. Generally, deep caries and trauma cause damage to the dentin-pulp complex, and if left untreated, this damage will progress to irreversible pulpitis. The aim of this study was to fabricate a layered cell sheet composed of rat dental pulp (DP) cells and odontogenic differentiation of pulp (OD) cells and to investigate the ability to regenerate the dentin-pulp complex in a scaffold tooth. We fabricated two single cell sheets composed of DP cells (DP cell sheet) or OD cells (OD cell sheet) and a layered cell sheet made by layering both cells. The characteristics of the fabricated cell sheets were analyzed using light microscopy, scanning electron microscope (SEM), hematoxylin-eosin (HE) staining, and immunohistochemistry (IHC). Furthermore, the cell sheets were transplanted into the subrenal capsule of immunocompromised mice for 8 weeks. After this, the regenerative capacity to form dentin-like tissue was evaluated using micro-computed tomography (micro-CT), HE staining, and IHC. The findings of SEM and IHC confirmed that layered cell sheets fabricated by stacking OD cells and DP cells maintained their cytological characteristics. Micro-CT of layered cell sheet transplants revealed a mineralized capping of the access cavity in the crown area, similar to that of natural dentin. In contrast, the OD cell sheet group demonstrated the formation of irregular fragments of mineralized tissue in the pulp cavity, and the DP cell sheet did not develop any hard tissue. Moreover, bone volume/tissue volume (BV/TV) showed a significant increase in hard tissue formation in the layered cell sheet group compared with that in the single cell sheet group ( < 0.05). HE staining also showed a combination of soft and hard tissue formation in the layered cell sheet group. Furthermore, IHC confirmed that the dentin-like tissue generated from the layered cell sheet expressed characteristic markers of dentin but not bone equivalent to that of a natural tooth. In conclusion, this study demonstrates the feasibility of regenerating dentin-pulp complex using a bioengineered tissue designed to simulate the anatomical structure. Impact statement The dentin-pulp complex can be destroyed by deep caries and trauma, which may cause pulpitis and progress to irreversible pulpitis, apical periodontitis, and even tooth loss. Current treatments cannot maintain pulp health, and teeth can become brittle. We developed a three-dimensional (3D) layered cell sheet using dental pulp cells and odontogenic differentiation of pulp cells for dentin-pulp complex regeneration. Our layered cell sheet enables the regeneration of an organized 3D dentin-pulp-like structure comparable with that of natural teeth. This layered cell sheet technology may contribute to dentin-pulp complex regeneration and provide a novel method for complex tissue engineering.


Longitudinal comparison between flipped classroom and team-based learning in a prosthodontic class

Active learning is a concept that allows students to study and learn actively by themselves to get knowledge. There are several methods of active learning, including flipped classroom (FC) and team-based learning (TBL). In FC, students are required to study before classes. In TBL, students also study before class, take individual readiness assurance test (iRAT) and team readiness assurance test (tRAT), then discuss group assignment projects (GAPs) during class. The purpose of this study was to compare the effectiveness between FC and TBL.
 The effectiveness of FC and TBL was assessed from the results of the term-end examinations, questionnaires and practice examinations. To check the difficulty of the term-end examinations, control dentists took the same examinations and we calculated the equating score with item response theory.
 Statistical analysis showed that the correct answer rate in term-end examinations was significantly different in comparison with the time of the trial, and for the participants (students and dentists). The term-end examination score of FC and TBL did not show a statistical difference. The student questionnaire showed that TBL had higher scores than FC on various factors such as student positive attitude, preparation, ingenuity of teacher and achieving the class goals. The crown & bridge score from the practice examination of 6th-year students who had FC + TBL were constantly higher than the Japanese national average score. The identification index of FC and TBL did not show the statistical difference and there was no statistical difference on item response theory between FC and TBL.


Risk factors for tooth loss in patients with 25 remaining teeth undergoing mid-long-term

International Journal of Environmental Research and Public Health


Mechanical homeostasis of liver sinusoid is involved in the initiation and termination of liver regeneration

Organogenesis and regeneration are fundamental for developmental progress and are associated with morphogenesis, size control and functional properties for whole-body homeostasis. The liver plays an essential role in maintaining homeostasis of the entire body through various functions, including metabolic functions, detoxification, and production of bile, via the three-dimensional spatial arrangement of hepatic lobules and has high regenerative capacity. The regeneration occurs as hypertrophy, which strictly controls the size and lobule structure. In this study, we established a three-dimensional sinusoidal network analysis method and determined valuable parameters after partial hepatectomy by comparison to the static phase of the liver. We found that mechanical homeostasis, which is crucial for organ morphogenesis and functions in various phenomena, plays essential roles in liver regeneration for both initiation and termination of liver regeneration, which is regulated by cytokine networks. Mechanical homeostasis plays critical roles in the initiation and termination of organogenesis, tissue repair and organ regeneration in coordination with cytokine networks.


インドネシアの歯学部における学部教育

インドネシアの歯学部における学部教育

The Journal of Japan Association of Oral Rehabilitation

日本口腔リハビリテーション学会雑誌


Immediate Effect of Masticatory Muscle Activity with Transcutaneous Electrical Nerve Stimulation in Muscle Pain of Temporomandibular Disorders Patients

Transcutaneous electrical nerve stimulation (TENS) is a non-invasive treatment modality for acute and chronic pain. However, little information for muscle activity is available on the immediate effects of TENS in masticatory muscle pain related to temporomandibular disorders (TMDs). The present study aimed to evaluate the immediate effects of TENS treatment on TMD-related muscle pain. Thirty-six patients with TMD-related muscle pain and 39 healthy subjects served as TMD and control groups, respectively. For objective evaluations, maximum mouth opening, and maximum bite force were measured before and after TENS. The pain intensity was assessed according to a 100-mm visual analog scale (VAS). TENS was applied to painful muscles for 20 min with frequencies of 100-200 Hz. The treatment outcome was evaluated using Global Rating of Change (GRC) scales. In the TMD group, VAS values significantly decreased after TENS. Although there was significant increase in the maximum mouth opening after TENS for only TMD group, the maximum bite force of both groups was significantly greater after TENS. According to GRC scales, one patient with TMD-related muscle pain expressed negative feelings after TENS. Conclusively, TENS treatment might quickly relieve pain in masticatory muscles and improve masticatory functions in patients with TMD-related muscle pain.


Risk factors for tooth loss in patients undergoing mid long-term maintenance: A retrospective study

In this retrospective study, we identified risk factors for tooth loss in patients undergoing mid-long-term maintenance therapy. We surveyed 674 maintenance patients for ≥5 years after active treatment who visited a dental clinic between January 2015 and December 2016. Of these, 265 were men (mean age 54.6 ± 8.0 years old) and 409 were women (mean age 54.0 ± 7.9 years old). Study variables included patient compliance, sex, number of teeth lost, cause of tooth loss (dental caries, periodontal disease, root fracture, others, vital or non-vital teeth), age at start of maintenance, number of remaining teeth at start of maintenance, smoking, use of salivary secretion inhibitors, presence of diabetes mellitus, condition of periodontal bone loss, and use of a removable denture. Most lost teeth were non-vital teeth (91.7% of all cases) and the most common cause of tooth loss was tooth fracture (62.1% of all cases). A statistically significant risk factors for tooth loss was number of remaining teeth at the start of maintenance ( = 0.003).


Role of CGRP in neuroimmune interaction via NFkB signalling genes in glial cells of trigeminal ganglia

Activation of the trigeminal system causes the release of various neuropeptides, cytokines, and other immune mediators. Calcitonin gene-related peptide (CGRP), which is a potent algogenic mediator, is expressed in the peripheral sensory neurons of trigeminal ganglion (TG). It affects the inflammatory responses and pain sensitivity by modulating the activity of glial cells. The primary aim of this study was to use array analysis to investigate the effect of CGRP on the glial cells of TG in regulating nuclear factor kappa B (NF-κB) signaling genes and to further check if CGRP in the TG can affect neuron-glia activation in the spinal trigeminal nucleus caudalis. The glial cells of TG were stimulated with CGRP or Minocycline (Min) + CGRP. The effect on various genes involved in NF-κB signaling pathway was analyzed compared to no treatment control condition using a PCR array analysis. CGRP, Min + CGRP or saline was directly injected inside the TG and the effect on gene expression of , and and protein expression of cleaved Caspase3 (cleav Casp3) in the TG, and c-Fos and glial fibrillary acidic protein (GFAP) in the spinal section containing trigeminal nucleus caudalis was analyzed. Results showed that CGRP stimulation resulted in the modulation of several genes involved in the interleukin 1 signaling pathway and some genes of the tumor necrosis factor pathway. Minocycline pre-treatment resulted in the modulation of several genes in the glial cells, including anti-inflammatory genes, and neuronal activation markers. A mild increase in cleav Casp3 expression in TG and c-Fos and GFAP in the spinal trigeminal nucleus of CGRP injected animals was observed. These data provide evidence that glial cells can participate in neuroimmune interaction due to CGRP in the TG via NF-κB signaling pathway.

International Journal of Molecular Sciences


Three-dimensional periodontal tissue regeneration using a bone-ligament complex cell sheet

Periodontal tissue is a distinctive tissue structure composed three-dimensionally of cementum, periodontal ligament (PDL) and alveolar bone. Severe periodontal diseases cause fundamental problems for oral function and general health, and conventional dental treatments are insufficient for healing to healthy periodontal tissue. Cell sheet technology has been used in many tissue regenerations, including periodontal tissue, to transplant appropriate stem/progenitor cells for tissue regeneration of a target site as a uniform tissue. However, it is still difficult to construct a three-dimensional structure of complex tissue composed of multiple types of cells, and the transplantation of a single cell sheet cannot sufficiently regenerate a large-scale tissue injury. Here, we fabricated a three-dimensional complex cell sheet composed of a bone-ligament structure by layering PDL cells and osteoblast-like cells on a temperature responsive culture dish. Following ectopic and orthotopic transplantation, only the complex cell sheet group was demonstrated to anatomically regenerate the bone-ligament structure along with the functional connection of PDL-like fibers to the tooth root and alveolar bone. This study represents successful three-dimensional tissue regeneration of a large-scale tissue injury using a bioengineered tissue designed to simulate the anatomical structure.


The role of chemical transmitters in neuron-glia interaction and pain in sensory ganglion

Neuropathic pain (NP) develops because of damage to the peripheral or central nervous system. It results in the hyperalgesia and allodynia. In the recent years, various researchers have studied the involvement of neuro-immune system in causing persistence of pain. The absence of synaptic contacts in the sensory ganglion makes them distinctive in terms of pain related signalling. In sensory ganglia, the neurotransmitters or the other modulators such as inflammatory substances produced by the ganglion cells, because of an injury, are responsible for the cross-excitation between neurons and neuron-glial interaction, thus affecting chemical transmission. This chemical transmission is considered mainly responsible for the chronicity and the persistent nature of neuropathic pain. This review examines the pain signalling due to neurotransmitter or cytokine release within the sensory ganglia. The specific areas focused on include: 1) the role of neurotransmitters released from the somata of sensory neurons in pain, 2) neuron-glia interaction and 3) role of cytokines in neuromodulation and pain.


Fibronectin-induced ductal formation in salivary gland self-organization model

Recent advances in tissue regeneration approaches including 3D organoids, were based on various 3D organogenesis models. However, 3D models are generally technique-sensitive and time-consuming. Thus, we utilized an existing model of submandibular salivary gland (SMG) to modify a simple and highly reproducible in vitro 3D culture model of primary SMG cells self-organization into a well-developed cell spheroid inside Matrigel substrate. We used this model to observe the collective multicellular behavior during spheroid formation. Further, we applied various quantitative approaches including real-time live imaging and immune histochemical image analysis to dissect the cellular dynamics during tissue patterning. On a time-scale of hours, we observed marked size and shape transformations in the developed 3D spheroid which resulted in a spatially-controlled growth differential from the canter to the periphery of the formed aggregates. Moreover, we investigated the effect of fibronectin (FN) on SMG cells self-organization using our simplified culture model. Interestingly, we discovered a novel role of FN in inducing duct-like elongation during initial stages of SMG bud formation. This in vitro model provides an excellent tool for analyzing the intercellular dynamics during early SMG tissue development as well as revealing a novel role of FN in SMG ductal expansion.


IL-10 and CXCL2 in trigeminal ganglia in neuropathic pain


Analysis of Bone Marrow-derived Mesenchymal Stem Cell Kinetics after Short-term Stimulation with Tumor Necrosis Factor-α (TNF-α)


Quality of life and job satisfaction among female dentists in Japan


CGRP induces differential regulation of cytokines from satellite glial cells in trigeminal ganglia and orofacial nociception

Neuron-glia interactions contribute to pain initiation and sustainment. Intra-ganglionic (IG) secretion of calcitonin gene-related peptide (CGRP) in the trigeminal ganglion (TG) modulates pain transmission through neuron-glia signaling, contributing to various orofacial pain conditions. The present study aimed to investigate the role of satellite glial cells (SGC) in TG in causing cytokine-related orofacial nociception in response to IG administration of CGRP. For that purpose, CGRP alone (10 μL of 10 M), Minocycline (5 μL containing 10 μg) followed by CGRP with one hour gap (Min + CGRP) were administered directly inside the TG in independent experiments. Rats were evaluated for thermal hyperalgesia at 6 and 24 h post-injection using an operant orofacial pain assessment device (OPAD) at three temperatures (37, 45 and 10 °C). Quantitative real-time PCR was performed to evaluate the mRNA expression of IL-1β, IL-6, TNF-α, IL-1 receptor antagonist (IL-1RA), sodium channel 1.7 (NaV 1.7, for assessment of neuronal activation) and glial fibrillary acidic protein (GFAP, a marker of glial activation). The cytokines released in culture media from purified glial cells were evaluated using antibody cytokine array. IG CGRP caused heat hyperalgesia between 6-24 h (paired- test, < 0.05). Between 1 to 6 h the mRNA and protein expressions of GFAP was increased in parallel with an increase in the mRNA expression of pro-inflammatory cytokines IL-1β and anti-inflammatory cytokine IL-1RA and NaV1.7 (one-way ANOVA followed by Dunnett's post hoc test, < 0.05). To investigate whether glial inhibition is useful to prevent nociception symptoms, Minocycline (glial inhibitor) was administered IG 1 h before CGRP injection. Minocycline reversed CGRP-induced thermal nociception, glial activity, and down-regulated IL-1β and IL-6 cytokines significantly at 6 h (-test, < 0.05). Purified glial cells in culture showed an increase in release of 20 cytokines after stimulation with CGRP. Our findings demonstrate that SGCs in the sensory ganglia contribute to the occurrence of pain via cytokine expression and that glial inhibition can effectively control the development of nociception.


Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis

Regenerative therapy to replace missing teeth is a critical area of research. Functional bioengineered teeth have been produced by the organ germ method using mouse tooth germ cells. However, these bioengineered teeth are significantly smaller in size and exhibit an abnormal crown shape when compared with natural teeth. The proper sizes and shapes of teeth contribute to their normal function. Therefore, a method is needed to control the morphology of bioengineered teeth. Here, we investigated whether insulin-like growth factor 1 (IGF1) can regulate the sizes and shapes of bioengineered teeth, and assessed underlying mechanisms of such regulation. IGF1 treatment significantly increased the size of bioengineered tooth germs, while preserving normal tooth histology. IGF1-treated bioengineered teeth, which were developed from bioengineered tooth germs in subrenal capsules and jawbones, showed increased sizes and cusp numbers. IGF1 increased the number of fibroblast growth factor (Fgf4)-expressing enamel knots in bioengineered tooth germs and enhanced the proliferation and differentiation of dental epithelial and mesenchymal cells. This study is the first to reveal that IGF1 increases the sizes and cusp numbers of bioengineered teeth via the induction of enamel knot formation, as well as the proliferation and differentiation of dental epithelial and mesenchymal cells.


Effect of short-term Tumour Necrosis Factor-alpha (TNF-α) -stimulation on the growth and differentiation of MC3T3-E1 osteoblast-like cells


Radiographic investigation of the marginal bone loss on dental implants, a retrospective cohort study

Background: During functional loading, the design of the dental implant may have an effect on the response of marginal bone.
Objectives: The purpose of this study was to report the prevalence of peri-implantitis, and to compare radiographic parameters around Brånemark and Replace Select dental implants and evaluate whether disparities in the morphologic features of these two indistinct implant systems, particularly their abutment-implant attachment, had an influence on the health of surrounding tissues and marginal bone loss (MBL).
Materials and Methods: Collection of data was done at the Department of Fixed Prosthodontics, the Department of Maxillo-Facial Prosthodontics, and Oral Implant Center of Tokushima University Hospital, in Tokushima, Japan; between March 2003 and followed until January 2017. Patients who have been treated with the Replace Select internal type implant and the Brånemark variety were selected as cohort. Marginal bone level measurements were evaluated via periapical and panoramic radiographs taken at regular follow-up visit. These dimensions were calculated, starting from the orientation mark at the implant abutment interface to the bottommost perceived contact area of marginal bone with the aforementioned implant system. The change in the level of bone was estimated by calculating the variation involving an initial reference value and the follow-up values.
Results: An average loss of bone at 0.65 ± 1.51 mm (range 0.36 to 7.89 mm) in the Replace Select group was observed, while in the Brånemark group 0.7 ± 1.32 mm (range 0.62 to 8.64 mm) was observed. Spearman rank correlation exhibited a statistically significant positive correlation between progress of bone loss around implant body and interval from implantation in the Brånemark group, whereas in the Replace Select group it was not significant. The Brånemark group exhibited significant (P = 0.0269) negative correlation of MBL and its diameters, whereas the Replace Select group did not exhibit such correlation.
Conclusion: Within the limits of this study, it can be concluded that deviations in the morphologic attributes of these two diverse implant systems had an influence on the health of surrounding tissues and MBL. The Brånemark implants showed a significant increase in MBL (> 1.8mm) as the time of placement elapses. This marked MBL was greater in females than males, in posterior than in anterior, and in the narrow platform implants than the regular platform implants or the wide platform implants. On the other hand, results suggested that this bone loss was greater in the mandible than the maxilla, in single-unit implant crowns than multiple implant restorations in the Replace Select group.

Background: During functional loading, the design of the dental implant may have an effect on the response of marginal bone.Objectives: The purpose of this study was to report the prevalence of peri-implantitis, and to compare radiographic parameters around Brånemark and Replace Select dental implants and evaluate whether disparities in the morphologic features of these two indistinct implant systems, particularly their abutment-implant attachment, had an influence on the health of surrounding tissues and marginal bone loss (MBL).Materials and Methods: Collection of data was done at the Department of Fixed Prosthodontics, the Department of Maxillo-Facial Prosthodontics, and Oral Implant Center of Tokushima University Hospital, in Tokushima, Japan; between March 2003 and followed until January 2017. Patients who have been treated with the Replace Select internal type implant and the Brånemark variety were selected as cohort. Marginal bone level measurements were evaluated via periapical and panoramic radiographs taken at regular follow-up visit. These dimensions were calculated, starting from the orientation mark at the implant abutment interface to the bottommost perceived contact area of marginal bone with the aforementioned implant system. The change in the level of bone was estimated by calculating the variation involving an initial reference value and the follow-up values.Results: An average loss of bone at 0.65 ± 1.51 mm (range 0.36 to 7.89 mm) in the Replace Select group was observed, while in the Brånemark group 0.7 ± 1.32 mm (range 0.62 to 8.64 mm) was observed. Spearman rank correlation exhibited a statistically significant positive correlation between progress of bone loss around implant body and interval from implantation in the Brånemark group, whereas in the Replace Select group it was not significant. The Brånemark group exhibited significant (P = 0.0269) negative correlation of MBL and its diameters, whereas the Replace Select group did not exhibit such correlation.Conclusion: Within the limits of this study, it can be concluded that deviations in the morphologic attributes of these two diverse implant systems had an influence on the health of surrounding tissues and MBL. The Brånemark implants showed a significant increase in MBL (> 1.8mm) as the time of placement elapses. This marked MBL was greater in females than males, in posterior than in anterior, and in the narrow platform implants than the regular platform implants or the wide platform implants. On the other hand, results suggested that this bone loss was greater in the mandible than the maxilla, in single-unit implant crowns than multiple implant restorations in the Replace Select group.


咬合違和感の診断と対処法

咬合違和感の診断と対処法


Regeneration of complex oral organs using 3D cell organization technology

The development of organoid techniques for regenerative therapy has progressed remarkably with the use of tissue-derived stem cells and pluripotent stem cells based on stem cell biology and tissue engineering technology. To realize whole-organ replacement therapy as next-generation regenerative medicine, it is expected that fully functional bioengineered organs can be reconstructed using an in vitro three-dimensional (3D) bioengineered organ germ and organoids by stem cell manipulation and self-organization. In this mini-review, we focused on substantial advances of 3D bioengineering technologies for the regeneration of complex oral organs with the reconstruction of 3D bioengineered organ germ using organ-inductive potential embryo-derived epithelial and mesenchymal cells. These bioengineering technologies have the potential for realization of future organ replacement therapy.


Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model.

Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine.


Challenges for stem cell-based "regenerative prosthodontics".