Rare Case of First Permanent Molar Primary Failure of Eruption with Agenesis of Premolars.

Primary failure of eruption (PFE) is a rare non-syndromic condition involving total or partial non-eruption of posterior teeth in the absence of mechanical obstruction. This paper presents the case of a healthy girl referred at age 4 for asymmetry of the upper arch. Clinical examination confirmed a slight shift of the upper midline to the left, with no erupted teeth distal to the upper left canine and a left posterior open bite. Panoramic X-rays showed delayed intraosseous development of the lateral left upper teeth compared to the right side. Clinic and radiographic follow-up during the next 9 years showed that 26 had not erupted by almost 13 years of age, 27 had delayed development and an unusual shape, and there was an agenesis in 24 and 25. Genetic analysis using the PTH1R single-gene sequencing method did not detect any known disease-causing or rare pathogenic variants that could explain the patient's phenotype. Even when detected early, PFE raises difficult problems with regard to diagnosis and ortho-surgical treatment planning due to the impossibility of accurately predicting its evolution. Tooth agenesis on the same arch worsens the prognosis and adds challenges to planning the treatment. Close long-term follow-up and timely adjustment of the treatment plan in accordance with the evolution of the case are needed.

[Aesthetic rehabilitation of a case of maxillary fibrous dysplasia in a child]. / Réhabilitation esthétique d'un cas de dysplasie fibreuse maxillaire chez l'enfant.

Fibrous dysplasia (FD) is a rare, congenital, benign bone disorder in which healthy bone tissue is replaced by abnormal scar-like (fibrous) connective tissue. The lesions may affect one or more bones, including the jawbones. A 13-year-old girl visited the dentist for failed eruption of her left maxillary permanent teeth and facial asymmetry. Radiological analysis revealed impactions of the permanent teeth in hypertrophic, hyperdense, weakly trabeculated bone tissue. To restore the aesthetics of the smile, a treatment combining decoronation and bonded restorations was performed. FD enlargement would slow down after puberty, allowing for long-term therapies. But there is no information about implantology in this type of bone lesion. The aesthetic and functional consequences of a maxillary FD should be managed as soon as possible. Treatment involves a multidisciplinary team and follow-up care into adulthood.

Influence of Child's Temperament on Behaviour Management Problems in the Dental Office: A Literature Review.

BACKGROUND: A child's temperament could have an influence on his/her behaviour in the dental environment. This review aims to present the main temperament surveys and their clinical use and to discuss the relationship between certain temperament dimensions and Dental Behaviour Management Problems (DBMP). METHODS: A literature search was conducted in Medline/PubMed, ScienceDirect, Wiley Online Library and Cochrane library electronic databases for publications, up to June 2022, investigating the link between child's temperament and DBMP. RESULTS: From 733 potentially eligible studies, 12 were included in qualitative synthesis. CONCLUSION: According to studies using the Child Behaviour Questionnaire (CBQ) scale, the most impactful dimensions are activity, extraversion and surgency, high-intensity pleasure and attention control. For those using the Emotionality-Activity-Sociability (EAS) scale, emotionality and shyness have a statistically significant positive linear correlation with dental anxiety and DBMP. It has yet to be determined whether the use and interpretation of these questionnaires can be carried out in a daily clinical situation as an aid to sharpen the indications for the several levels of sedation.

[Representation of the oral sphere in medical comics, the child's perception]. / Représentation de la sphère buccale dans la bande dessinée médicale, la perception de l'enfant.

Medical comics are a suitable educational tool for paediatric populations. The emotions conveyed by the characters should not evoke negative feelings, which could then be associated with care or caregivers. The eyes and mouth are the first areas of the face to be analysed. One study attempted to assess the ability of children to perceive the emotions of one of the protagonists through the representation of their mouth.

Mechanistic Illustration: How Newly-Formed Blood Vessels Stopped by the Mineral Blocks of Bone Substitutes Can Be Avoided by Using Innovative Combined Therapeutics.

One major limitation for the vascularization of bone substitutes used for filling is the presence of mineral blocks. The newly-formed blood vessels are stopped or have to circumvent the mineral blocks, resulting in inefficient delivery of oxygen and nutrients to the implant. This leads to necrosis within the implant and to poor engraftment of the bone substitute. The aim of the present study is to provide a bone substitute currently used in the clinic with suitably guided vascularization properties. This therapeutic hybrid bone filling, containing a mineral and a polymeric component, is fortified with pro-angiogenic smart nano-therapeutics that allow the release of angiogenic molecules. Our data showed that the improved vasculature within the implant promoted new bone formation and that the newly-formed bone swapped the mineral blocks of the bone substitutes much more efficiently than in non-functionalized bone substitutes. Therefore, we demonstrated that our therapeutic bone substitute is an advanced therapeutical medicinal product, with great potential to recuperate and guide vascularization that is stopped by mineral blocks, and can improve the regeneration of critical-sized bone defects. We have also elucidated the mechanism to understand how the newly-formed vessels can no longer encounter mineral blocks and pursue their course of vasculature, giving our advanced therapeutical bone filling great potential to be used in many applications, by combining filling and nano-regenerative medicine that currently fall short because of problems related to the lack of oxygen and nutrients.

Eruption of Bioengineered Teeth: A New Approach Based on a Polycaprolactone Biomembrane.

Obtaining a functional tooth is the ultimate goal of tooth engineering. However, the implantation of bioengineered teeth in the jawbone of adult animals never allows for spontaneous eruption due mainly to ankylosis within the bone crypt. The objective of this study was to develop an innovative approach allowing eruption of implanted bioengineered teeth through the isolation of the germ from the bone crypt using a polycaprolactone membrane (PCL). The germs of the first lower molars were harvested on the 14th day of embryonic development, cultured in vitro, and then implanted in the recipient site drilled in the maxillary bone of adult mice. To prevent the ankylosis of the dental germ, a PCL membrane synthesized by electrospinning was placed between the germ and the bone. After 10 weeks of follow-up, microtomography, and histology of the implantation site were performed. In control mice where germs were directly placed in contact with the bone, a spontaneous eruption of bioengineered teeth was only observed in 3.3% of the cases versus 19.2% in the test group where PCL biomembrane was used as a barrier (p < 0.1). This preliminary study is the first to describe an innovative method allowing the eruption of bioengineered tooth implanted directly in the jawbone of mice. This new approach is a hope for the field of tooth regeneration, especially in children with oligodontia in whom titanium implants are not an optimal solution.

A New Polycaprolactone-Based Biomembrane Functionalized with BMP-2 and Stem Cells Improves Maxillary Bone Regeneration.

Oral diseases have an impact on the general condition and quality of life of patients. After a dento-alveolar trauma, a tooth extraction, or, in the case of some genetic skeletal diseases, a maxillary bone defect, can be observed, leading to the impossibility of placing a dental implant for the restoration of masticatory function. Recently, bone neoformation was demonstrated after in vivo implantation of polycaprolactone (PCL) biomembranes functionalized with bone morphogenic protein 2 (BMP-2) and ibuprofen in a mouse maxillary bone lesion. In the present study, human bone marrow derived mesenchymal stem cells (hBM-MSCs) were added on BMP-2 functionalized PCL biomembranes and implanted in a maxillary bone lesion. Viability of hBM-MSCs on the biomembranes has been observed using the "LIVE/DEAD" viability test and scanning electron microscopy (SEM). Maxillary bone regeneration was observed for periods ranging from 90 to 150 days after implantation. Various imaging methods (histology, micro-CT) have demonstrated bone remodeling and filling of the lesion by neoformed bone tissue. The presence of mesenchymal stem cells and BMP-2 allows the acceleration of the bone remodeling process. These results are encouraging for the effectiveness and the clinical use of this new technology combining growth factors and mesenchymal stem cells derived from bone marrow in a bioresorbable membrane.

Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss.

Secreted extracellular matrix components which regulate craniofacial development could be reactivated and play roles in adult wound healing. We report a patient with a loss-of-function of the secreted matricellular protein SMOC2 (SPARC related modular calcium binding 2) presenting severe oligodontia, microdontia, tooth root deficiencies, alveolar bone hypoplasia, and a range of skeletal malformations. Turning to a mouse model, Smoc2-GFP reporter expression indicates SMOC2 dynamically marks a range of dental and bone progenitors. While germline Smoc2 homozygous mutants are viable, tooth number anomalies, reduced tooth size, altered enamel prism patterning, and spontaneous age-induced periodontal bone and root loss are observed in this mouse model. Whole-genome RNA-sequencing analysis of embryonic day (E) 14.5 cap stage molars revealed reductions in early expressed enamel matrix components (Odontogenic ameloblast-associated protein) and dentin dysplasia targets (Dentin matrix acidic phosphoprotein 1). We tested if like other matricellular proteins SMOC2 was required for regenerative repair. We found that the Smoc2-GFP reporter was reactivated in adjacent periodontal tissues 4 days after tooth avulsion injury. Following maxillary tooth injury, Smoc2-/- mutants had increased osteoclast activity and bone resorption surrounding the extracted molar. Interestingly, a 10-day treatment with the cyclooxygenase 2 (COX2) inhibitor ibuprofen (30 mg/kg body weight) blocked tooth injury-induced bone loss in Smoc2-/- mutants, reducing matrix metalloprotease (Mmp)9. Collectively, our results indicate that endogenous SMOC2 blocks injury-induced jaw bone osteonecrosis and offsets age-induced periodontal decay.

Temporomandibular joint damage in K/BxN arthritic mice.

Rheumatoid arthritis (RA) is an autoimmune disease affecting 1% of the world population and is characterized by chronic inflammation of the joints sometimes accompanied by extra-articular manifestations. K/BxN mice, originally described in 1996 as a model of polyarthritis, exhibit knee joint alterations. The aim of this study was to describe temporomandibular joint (TMJ) inflammation and damage in these mice. We used relevant imaging modalities, such as micro-magnetic resonance imaging (µMRI) and micro-computed tomography (µCT), as well as histology and immunofluorescence techniques to detect TMJ alterations in this mouse model. Histology and immunofluorescence for Col-I, Col-II, and aggrecan showed cartilage damage in the TMJ of K/BxN animals, which was also evidenced by µCT but was less pronounced than that seen in the knee joints. µMRI observations suggested an increased volume of the upper articular cavity, an indicator of an inflammatory process. Fibroblast-like synoviocytes (FLSs) isolated from the TMJ of K/BxN mice secreted inflammatory cytokines (IL-6 and IL-1ß) and expressed degradative mediators such as matrix metalloproteinases (MMPs). K/BxN mice represent an attractive model for describing and investigating spontaneous damage to the TMJ, a painful disorder in humans with an etiology that is still poorly understood.

Application of Chitosan in Bone and Dental Engineering.

Chitosan is a deacetylated polysaccharide from chitin, the natural biopolymer primarily found in shells of marine crustaceans and fungi cell walls. Upon deacetylation, the protonation of free amino groups of the d-glucosamine residues of chitosan turns it into a polycation, which can easily interact with DNA, proteins, lipids, or negatively charged synthetic polymers. This positive-charged characteristic of chitosan not only increases its solubility, biodegradability, and biocompatibility, but also directly contributes to the muco-adhesion, hemostasis, and antimicrobial properties of chitosan. Combined with its low-cost and economic nature, chitosan has been extensively studied and widely used in biopharmaceutical and biomedical applications for several decades. In this review, we summarize the current chitosan-based applications for bone and dental engineering. Combining chitosan-based scaffolds with other nature or synthetic polymers and biomaterials induces their mechanical properties and bioactivities, as well as promoting osteogenesis. Incorporating the bioactive molecules into these biocomposite scaffolds accelerates new bone regeneration and enhances neovascularization in vivo.

Elements of morphology: Standard terminology for the teeth and classifying genetic dental disorders.

Dental anomalies occur frequently in a number of genetic disorders and act as major signs in diagnosing these disorders. We present definitions of the most common dental signs and propose a classification usable as a diagnostic tool by dentists, clinical geneticists, and other health care providers. The definitions are part of the series Elements of Morphology and have been established after careful discussions within an international group of experienced dentists and geneticists. The classification system was elaborated in the French collaborative network "TÊTECOU" and the affiliated O-Rares reference/competence centers. The classification includes isolated and syndromic disorders with oral and dental anomalies, to which causative genes and main extraoral signs and symptoms are added. A systematic literature analysis yielded 408 entities of which a causal gene has been identified in 79%. We classified dental disorders in eight groups: dental agenesis, supernumerary teeth, dental size and/or shape, enamel, dentin, dental eruption, periodontal and gingival, and tumor-like anomalies. We aim the classification to act as a shared reference for clinical and epidemiological studies. We welcome critical evaluations of the definitions and classification and will regularly update the classification for newly recognized conditions.

Polymer-Based Instructive Scaffolds for Endodontic Regeneration.

The challenge of endodontic regeneration is modulated by clinical conditions which determine five kinds of tissue requirements: pulp connective-tissue formation, dentin formation, revascularization, reinnervation and radicular edification. Polymer scaffolds constitute keystone of the different endodontic regenerative strategies. Indeed, scaffolds are crucial for carrying active molecules and competent cells which optimize the regeneration. Hydrogels are very beneficial for controlling viscosity and porosity of endodontic scaffolds. The nanofibrous and microporous scaffolds mimicking extracellular matrix are also of great interest for promoting dentin-pulp formation. Two main types of polymer scaffolds are highlighted: collagen and fibrin. Collagen scaffolds which are similar to native pulp tissue, are adequate for pulp connective tissue formation. Functionnalization by active biomolecules as BMP, SDF-1, G-CSF enhances their properties. Fibrin or PRF scaffolds present the advantage of promoting stem cell differentiation and concomitant revascularisation. The choice of the type of polymers (polypeptide, PCL, chitosan) can depend on its ability to deliver the active biomolecule or to build as suitable hydrogel as possible. Since 2010s, proposals to associate different types of polymers in a same scaffold have emerged for adding advantages or for offsetting a disadvantage of a polymer. Further works would study the synergetic effects of different innovative polymers composition.

Periodontal Tissues, Maxillary Jaw Bone, and Tooth Regeneration Approaches: From Animal Models Analyses to Clinical Applications.

This review encompasses different pre-clinical bioengineering approaches for periodontal tissues, maxillary jaw bone, and the entire tooth. Moreover, it sheds light on their potential clinical therapeutic applications in the field of regenerative medicine. Herein, the electrospinning method for the synthesis of polycaprolactone (PCL) membranes, that are capable of mimicking the extracellular matrix (ECM), has been described. Furthermore, their functionalization with cyclosporine A (CsA), bone morphogenetic protein-2 (BMP-2), or anti-inflammatory drugs' nanoreservoirs has been demonstrated to induce a localized and targeted action of these molecules after implantation in the maxillary jaw bone. Firstly, periodontal wound healing has been studied in an induced periodontal lesion in mice using an ibuprofen-functionalized PCL membrane. Thereafter, the kinetics of maxillary bone regeneration in a pre-clinical mouse model of surgical bone lesion treated with BMP-2 or BMP-2/Ibuprofen functionalized PCL membranes have been analyzed by histology, immunology, and micro-computed tomography (micro-CT). Furthermore, the achievement of innervation in bioengineered teeth has also been demonstrated after the co-implantation of cultured dental cell reassociations with a trigeminal ganglia (TG) and the cyclosporine A (CsA)-loaded poly(lactic-co-glycolic acid) (PLGA) scaffold in the jaw bone. The prospective clinical applications of these different tissue engineering approaches could be instrumental in the treatment of various periodontal diseases, congenital dental or cranio-facial bone anomalies, and post-surgical complications.

Maxillary Bone Regeneration Based on Nanoreservoirs Functionalized ε-Polycaprolactone Biomembranes in a Mouse Model of Jaw Bone Lesion.

Current approaches of regenerative therapies constitute strategies for bone tissue reparation and engineering, especially in the context of genetical diseases with skeletal defects. Bone regeneration using electrospun nanofibers' implant has the following objectives: bone neoformation induction with rapid healing, reduced postoperative complications, and improvement of bone tissue quality. In vivo implantation of polycaprolactone (PCL) biomembrane functionalized with BMP-2/Ibuprofen in mouse maxillary defects was followed by bone neoformation kinetics evaluation using microcomputed tomography. Wild-Type (WT) and Tabby (Ta) mice were used to compare effects on a normal phenotype and on a mutant model of ectodermal dysplasia (ED). After 21 days, no effect on bone neoformation was observed in Ta treated lesion (4% neoformation compared to 13% in the control lesion). Between the 21st and the 30th days, the use of biomembrane functionalized with BMP-2/Ibuprofen in maxillary bone lesions allowed a significant increase in bone neoformation peaks (resp., +8% in mutant Ta and +13% in WT). Histological analyses revealed a neoformed bone with regular trabecular structure, areas of mineralized bone inside the membrane, and an improved neovascularization in the treated lesion with bifunctionalized membrane. In conclusion, PCL functionalized biomembrane promoted bone neoformation, this effect being modulated by the Ta bone phenotype responsible for an alteration of bone response.

Temporomandibular Joint Regenerative Medicine.

The temporomandibular joint (TMJ) is an articulation formed between the temporal bone and the mandibular condyle which is commonly affected. These affections are often so painful during fundamental oral activities that patients have lower quality of life. Limitations of therapeutics for severe TMJ diseases have led to increased interest in regenerative strategies combining stem cells, implantable scaffolds and well-targeting bioactive molecules. To succeed in functional and structural regeneration of TMJ is very challenging. Innovative strategies and biomaterials are absolutely crucial because TMJ can be considered as one of the most difficult tissues to regenerate due to its limited healing capacity, its unique histological and structural properties and the necessity for long-term prevention of its ossified or fibrous adhesions. The ideal approach for TMJ regeneration is a unique scaffold functionalized with an osteochondral molecular gradient containing a single stem cell population able to undergo osteogenic and chondrogenic differentiation such as BMSCs, ADSCs or DPSCs. The key for this complex regeneration is the functionalization with active molecules such as IGF-1, TGF-ß1 or bFGF. This regeneration can be optimized by nano/micro-assisted functionalization and by spatiotemporal drug delivery systems orchestrating the 3D formation of TMJ tissues.

[Preventive and therapeutic advantages of sugar-free chewing gums in orthodontics. A study conducted on practitioners and patients]. / Intérêt prophylactique et thérapeutique des chewing-gums sans sucre en orthodontie. Une étude menée auprès de professionnels de santé et de patients.

OBJECTIVE: The objective of this study is to assess the level of knowledge in a cohort of oral health professionals and patients about preventive and therapeutic actions of sugar-free chewing gums. MATERIALS AND METHODS: A forward-looking monocentric study of perception regarding the level of information about the effects of sugar-free chewing gums consumption was conducted on 135 young patients, from 11 to 17 years old, carriers of fixed orthodontic appliances and treated in the Department of Orthodontics in the Oral Medicine and Surgery Center of the University Hospitals of Strasbourg. Besides, 34 practitioners in the Department of Orthodontics and Pediatric Dentistry were also included. Data were collected between May 2016 and July 2016. A specific questionnaire, using the adapted terminology and dealing with the same items was developed for each studied population. RESULTS: The majority of the individuals of both studied populations believe that the consumption of sugar-free chewing gum leads to a greater risk of orthodontic device unsticking or fracture and that it is not associated to a decrease of the orthodontic pain. DISCUSSION: Our results confirm the fact that the knowledge, mainly acquired in an empirical way, is against the data of the current literature. The evaluation of the level of knowledge demonstrated that there is a real lack of information about the preventive interests of the consumption of sugar-free chewing gums during orthodontic treatment. CONCLUSIONS: This study highlights the need for information campaigns and oral prevention in general population, as well as in healthcare professionals, concerning the preventive and analgesic interests of sugar-free chewing gums during orthodontic treatments.

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.

Angiotensin-converting enzyme inhibition prevents myocardial infarction-induced increase in renal cortical cGMP and cAMP phosphodiesterase activities.

We investigated whether myocardial infarction (MI) enhances renal phosphodiesterases (PDE) activities, investigating particularly the relative contribution of PDE1-5 isozymes in total PDE activity involved in both cGMP and cAMP pathways, and whether angiotensin-converting enzyme inhibition (ACEi) decreases such renal PDE hyperactivities. We also investigated whether ACEi might thereby improve atrial natriuretic peptide (ANP) efficiency. We studied renal cortical PDE1-5 isozyme activities in sham (SH)-operated, MI rats and in MI rats treated with perindopril (ACEi) 1 month after coronary artery ligation. Circulating atrial natriuretic peptide (ANP), its second intracellular messenger cyclic guanosine monophosphate (cGMP) and cGMP/ANP ratio were also determined. Cortical cGMP-PDE2 (80.3 vs. 65.1 pmol/min/mg) and cGMP-PDE1 (50.7 vs. 30.1 pmol/min/mg), and cAMP-PDE2 (161 vs. 104.1 pmol/min/mg) and cAMP-PDE4 (307.5 vs. 197.2 pmol/min/mg) activities were higher in MI than in SH rats. Despite increased ANP plasma level, ANP efficiency tended to be decreased in MI compared to SH rats. Perindopril restored PDE activities and tended to improve ANP efficiency in MI rats. One month after coronary ligation, perindopril treatment of MI rats prevents the increase in renal cortical PDE activities. This may contribute to increase renal ANP efficiency in MI rats.

Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta.

Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder.

Nanostructured thick 3D nanofibrous scaffold can induce bone.

Designing unique nanostructured biomimetic materials is a new challenge in modern regenerative medicine. In order to develop functional substitutes for damaged organs or tissues, several methods have been used to create implants able to regenerate robust and durable bone. Electrospinning produces nonwoven scaffolds based on polymer nanofibers mimicking the fibrillar organization of bone extracellular matrix. Here, we describe a biomimetic 3D thick nanofibrous scaffold obtained by electrospinning of the biodegradable, bioresorbable and FDA-approved polymer, poly(ε-caprolactone). Such scaffold presents a thickness reaching one centimeter. We report here the demonstration that the designed nanostructured implant is able to induce in vivo bone regeneration.