Role of Physico-Chemical and Cellular Conditions on the Bone Repair Potential of Plastically Compressed Collagen Hydrogels.

Since their first description nearly 20 years ago, dense collagen hydrogels obtained by plastic compression have become popular scaffolds in tissue engineering. In particular, when seeded with dental pulp stem cells, they have demonstrated a great in vivo potential in cranial bone repair. Here, we investigated how physico-chemical and cell-seeding conditions could influence the formation and in vitro mineralization of these cellularized scaffolds. A qualitative assessment demonstrated that the gel stability before and after compression was highly sensitive to the conditions of fibrillogenesis, especially initial acid acetic and buffer concentrations. Gels with similar rheological properties but different fibrillar structures that exhibited different stabilities when used for the 3D culture of Stem cells from Human Exfoliated Deciduous teeth (SHEDs) could be prepared. Finally, in our optimal physico-chemical conditions, mineralization could be achieved only using human dental pulp stem cells (hDPSCs) at a high cell density. These results highlight the key role of fibrillogenic conditions and cell type/density on the bone repair potential of cell-laden plastically compressed collagen hydrogels.

Combining sclerostin neutralization with tissue engineering: An improved strategy for craniofacial bone repair.

Scaffolds associated with different types of mesenchymal stromal stem cells (MSC) are extensively studied for the development of novel therapies for large bone defects. Moreover, monoclonal antibodies have been recently introduced for the treatment of cancer-associated bone loss and other skeletal pathologies. In particular, antibodies against sclerostin, a key player in bone remodeling regulation, have demonstrated a real benefit for treating osteoporosis but their contribution to bone tissue-engineering remains uncharted. Here, we show that combining implantation of dense collagen hydrogels hosting wild-type (WT) murine dental pulp stem cells (mDPSC) with weekly systemic injections of a sclerostin antibody (Scl-Ab) leads to increased bone regeneration within critical size calvarial defects performed in WT mice. Furthermore, we show that bone formation is equivalent in calvarial defects in WT mice implanted with Sost knock-out (KO) mDPSC and in Sost KO mice, suggesting that the implantation of sclerostin-deficient MSC similarly promotes new bone formation than complete sclerostin deficiency. Altogether, our data demonstrate that an antibody-based therapy can potentialize tissue-engineering strategies for large craniofacial bone defects and urges the need to conduct research for antibody-enabled local inhibition of sclerostin. STATEMENT OF SIGNIFICANCE: The use of monoclonal antibodies is nowadays broadly spread for the treatment of several conditions including skeletal bone diseases. However, their use to potentialize tissue engineering constructs for bone repair remains unmet. Here, we demonstrate that the neutralization of sclerostin, through either a systemic inhibition by a monoclonal antibody or the implantation of sclerostin-deficient mesenchymal stromal stem cells (MSC) directly within the defect, improves the outcome of a tissue engineering approach, combining dense collagen hydrogels and MSC derived from the dental pulp, for the treatment of large craniofacial bone defects.

Dental phenotype in Crouzon syndrome: A controlled radiographic study in 22 patients.

OBJECTIVE: This retrospective radiographic controlled study investigates the dental phenotype in patients with Crouzon syndrome to determine if differences are observed as suggested by the FGFR2C342Y/+ Crouzon mouse models, and whether these models could be of interest to study the role of this mutation in tooth development. DESIGN: We assessed dental phenotype using dedicated linear measurements in 22 children with Crouzon syndrome and compared tooth morphology in both primary and permanent dentitions to an age-matched control group. Descriptive statistics were performed with "Sex" and "Age" as covariates for the permanent tooth models and "Sex" only for the primary tooth models, to take into account potential confounding factors. RESULTS: We showed that permanent but not primary tooth dimensions were globally reduced in Crouzon syndrome, without microdontia. In permanent dentition, crown height, mesiodistal and faciolingual cervical diameters were reduced by 6.3%, 5.7% and 5.5% respectively (p < 0.05). CONCLUSION: Our results underline the implication of Fibroblast Growth Factor Receptor 2 (FGFR2) in dental development of humans and contribute to support FGFR2C342Y/+ Crouzon mouse models as partial replicas of this condition, including in the oral region.

In-house 3D printing: Why, when, and how? Overview of the national French good practice guidelines for in-house 3D-printing in maxillo-facial surgery, stomatology, and oral surgery.

3D-printing is part of the daily practice of maxillo-facial surgeons, stomatologists and oral surgeons. To date, no French health center is producing in-house medical devices according to the new European standards. Based on all the evidence-based data available, a group of experts from the French Society of Stomatology, Maxillo-Facial Surgery and Oral Surgery (Société Française de Chirurgie Maxillofaciale, Stomatologie et Chirurgie Orale, SFSCMFCO), provide good practice guidelines for in-house 3D-printing in maxillo-facial surgery, stomatology, and oral surgery. Briefly, technical considerations related to printers and CAD software, which were the main challenges in the last ten years, are now nearly trivial questions. The central current issues when planning the implementation of an in-house 3D-printing platform are economic and regulatory. Successful in-house 3D platforms rely on close collaborations between health professionals and engineers, backed by regulatory and logistic specialists. Several large-scale academic projects across France will soon provide definitive answers to governance and economical questions related to the use of in-house 3D printing.

Dental consequences of pterygomaxillary dysjunction during fronto-facial monobloc advancement with internal distraction for Crouzon syndrome.

Crouzon syndrome is a syndromic faciocraniosynostosis that can be associated with severe fronto-facial retrusion leading to major functional impairments: extreme exorbitism may be vision-threatening and severe respiration impairment can be life-threatening. The procedure of choice for the primary correction of this retrusion is fronto-facial monobloc advancement (FFMBA) with internal or external distraction. FFMBA involves pterygomaxillary dysjunction (PMD), using either a superior or an intra-oral approach. This step is at risk of damaging the germs of the decidual and permanent molars. Here we considered a series of 15 patients with Crouzon syndrome who benefited from FFMBA performed by the same surgeon, using a superior approach through the infra-temporal fossa for PMD. Based on pre-operative, early post-operative and late post-operative CT-scans, we recorded missing teeth, morphological dental anomalies and the Nolla stage for the first and second permanent maxillary molars. We showed that early FFMBA has significant dental consequences, and that these dental effects are correlated with an early age at surgery. Although the indications of early FFMBA in Crouzon syndrome with severe functional repercussions are not questionable, our results should be compared to dental outcomes of FFMBA performed with an intra-oral PMD.

Bilateral Dislocation of the Temporomandibular Joint in Children.

PURPOSE: Bilateral nontraumatic temporomandibular joint (TMJ) dislocation is an acute situation that can lead to a chronic and recurrent condition. Few pediatric cases have been reported in the literature and no standardized care protocol has been established to date. MATERIALS AND METHODS: Two cases of chronic bilateral dislocation of the TMJ in young children are reported and their medical management is discussed based on data from the literature. RESULTS: A 26 months-old child and a 19-months old child were included. Both had chronic bilateral TMJ dislocation managed using a combination of reduction under nitrous oxide sedation, reduction under general anesthesia, chin-to-vertex bandage and orthodontic headgear. CONCLUSION: TMJ dislocations in children raise specific concerns such as the need for screening for underlying congenital disorders of connective tissues. Furthermore, surgical options in children are very limited. The authors propose a standardized management protocol for recurrent joint dislocation in pediatric populations based on 2 new cases and data from the literature.