Primary failure of eruption and tooth resorption / Défaut primaire d'éruption et résorption radiculaire externe

Introduction: The number of adult patients who seek an orthodontic treatment is increasing. These Primary failure of eruption (PFE) is defined as the partial or complete failure of eruption of at least one posterior tooth, without any mechanical obstacle. A better understanding of the biological mechanisms involved in PFE would enable to refine the diagnostic and prognostic criteria. This rare disease is currently related to PTHR1 gene variants. This gene codes for a transmembrane receptor involved in bone metabolism. However, there is few evidence associating PFE and bone remodeling abnormalities such as external root resorption. External root resorption is the loss of cementum and dentin tissues, resulting from the activation of clastic cells. Materials and Methods: Human teeth affected by PFE were extracted and histological sections were made after fixation of the tissues in 4% PFA. The observations were correlated with three-dimensional imaging by cone beam computed tomography (CBCT) carried out in the preoperative phase. Results: Histological and radiographic analysis confirm the presence of ankylosis area in patients with no history of orthodontic treatment. Large areas of resorption of external root replacement were detected. Discussion: The results call the causal link between the appearance of ankylosis areas and the establishment of orthodontic traction in patients with PFE into question. The installation of an orthodontic force in this context could be only an aggravating factor, accelerating the processes of ankylosis or triggering them more prematurely. Conclusion: With or without orthodontic treatment, teeth with PFE are likely to progress to ankylosis and resorption of replacement external root.

Introduction: Les défauts primaires d'éruption (DPE) se caractérisent par l'échec total ou partiel de l'éruption d'une ou plusieurs dents postérieures, sans obstacle mécanique. Une meilleure compréhension des mécanismes biologiques impliqués dans les DPE permettrait d'affiner les critères diagnostiques et pronostiques. Cette pathologie rare est actuellement imputée à des variants du gène PTHR1. Ce gène code pour un récepteur transmembranaire impliqué dans le métabolisme osseux. Cependant, on trouve peu de données associant DPE et anomalies du remodelage osseux de type résorption radiculaire externe. La résorption radiculaire externe correspond à la perte de tissus cémentaire et dentinaire résultant de l'activation de cellules clastiques. Matériels et méthodes: Des dents d'origine humaine atteintes de DPE ont été avulsées et des coupes histologiques réalisées après fixation des tissus. Les observations ont été corrélées avec l'imagerie tridimensionnelle par tomographie volumique à faisceau conique (TVFC ou encore CBCT). Résultats: Les analyses histologiques et radiographiques montrent la présence de plage d'ankylose chez des patients sans antécédent de prise en charge orthodontique. De larges zones de résorptions radiculaires externes de remplacement ont été détectées. Discussion: Les résultats remettent en cause le lien de causalité entre l'apparition d'ankylose et la mise en place de traction orthodontique chez les patients atteints de DPE. La mise en place d'une force orthodontique dans ce contexte pourrait n'être qu'un facteur aggravant, accélérant les processus d'ankylose ou les déclenchant plus prématurément. Conclusion: Avec ou sans traitement orthodontique, les dents atteintes de DPE sont susceptibles d'évoluer vers l'ankylose et la résorption radiculaire externe de remplacement.

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.

Semaphorin 3A receptor inhibitor as a novel therapeutic to promote innervation of bioengineered teeth.

The sensory innervation of the dental pulp is essential for tooth function and protection. It is mediated by axons originating from the trigeminal ganglia and is spatio-temporally regulated. We have previously shown that the innervation of bioengineered teeth can be achieved only under immunosuppressive conditions. The aim of this study was to develop a model to determine the role of Semaphorin 3A (Sema3A) in the innervation of bioengineered teeth. We first analysed innervation of the dental pulp of mandibular first molars in newborn (postnatal day 0: PN0) mice deficient for Sema3A (Sema3A-/- ), a strong inhibitor of axon growth. While at PN0, axons detected by immunostaining for peripherin and NF200 were restricted to the peridental mesenchyme in Sema3A+/+ mice, they entered the dental pulp in Sema3A-/- mice. Then, we have implanted cultured teeth obtained from embryonic day-14 (E14) molar germs of Sema3A-/- mice together with trigeminal ganglia. The dental pulps of E14 cultured and implanted Sema3A-/- teeth were innervated, whereas the axons did not enter the pulp of E14 Sema3A+/+ cultured and implanted teeth. A "Membrane Targeting Peptide NRP1," suppressing the inhibitory effect of Sema3A, has been previously identified. The injection of this peptide at the site of implantation allowed the innervation of the dental pulp of bioengineered teeth obtained from E14 dental dissociated mesenchymal and epithelial cells reassociations of ICR mice. In conclusion, these data show that inhibition of only one axon repellent molecule, Sema3A, allows for pulp innervation of bioengineered teeth.

Combining 2D angiogenesis and 3D osteosarcoma microtissues to improve vascularization.

Angiogenesis is now well known for being involved in tumor progression, aggressiveness, emergence of metastases, and also resistance to cancer therapies. In this study, to better mimic tumor angiogenesis encountered in vivo, we used 3D culture of osteosarcoma cells (MG-63) that we deposited on 2D endothelial cells (HUVEC) grown in monolayer. We report that endothelial cells combined with tumor cells were able to form a well-organized network, and that tubule-like structures corresponding to new vessels infiltrate tumor spheroids. These vessels presented a lumen and expressed specific markers as CD31 and collagen IV. The combination of 2D endothelial cells and 3D microtissues of tumor cells also increased expression of angiogenic factors as VEGF, CXCR4 and ICAM1. The cell environment is the key point to develop tumor vascularization in vitro and to be closer to tumor encountered in vivo.

Hybrid collagen sponge and stem cells as a new combined scaffold able to induce the re-organization of endothelial cells into clustered networks.

The time needed to obtain functional regenerated bone tissue depends on the existence of a reliable vascular support. Current techniques used in clinic, for example after tooth extraction, do not allow regaining or preserving the same bone volume. Our aim is to develop a cellularized active implant of the third generation, equipped with human mesenchymal stem cells to improve the quality of implant vascularization. We seeded a commercialized collagen implant with human mesenchymal stem cells (hMSCs) and then with human umbilical vein endothelial cells (HUVECs). We analyzed the biocompatibility and the behavior of endothelial cells with this implant. We observed a biocompatibility of the active implant, and a re-organization of endothelial cells into clustered networks. This work shows the possibility to develop an implant of the third generation supporting vascularization, improving the medical care of patients.