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Regeneration of orofacial tissues is hampered by the lack of adequate vascular supply. Implantation of in vitro engineered, prevascularized constructs has emerged as a strategy to allow the rapid vascularization of the entire graft. Given the angiogenic properties of dental pulp stem cells, we hereby established a preclinical model of prevascularized constructs loaded with stem cells from human exfoliating deciduous teeth (SHED) in a 3-dimensional-printed material and provided a functional analysis of their in vivo angiogenesis, vascular perfusion, and permeability. Three different cell-loaded collagen hydrogels (SHED–human umbilical vein endothelial cell [HUVEC], HUVEC with SHED-conditioned medium, and SHED alone) were cast in polylactic acid (PLA) grids and ectopically implanted in athymic mice. At day 10, in vivo positron emission tomography (PETscan) revealed a significantly increased uptake of radiotracer targeting activated endothelial cells in the SHED-HUVEC group compared to the other groups. At day 30, ex vivo micro–computed tomography imaging confirmed that SHED-HUVEC constructs had a significantly increased vascular volume compared to the other ones. Injection of species-specific lectins analyzed by 2-photon microscopy demonstrated blood perfusion of the engineered human vessels in both prevascularized groups. However, in vivo quantification showed increased vessel density in the SHED-HUVEC group. In addition, coinjection of fluorescent lectin and dextran revealed that prevascularization with SHED prevented vascular leakage, demonstrating the active role of SHED in the maturation of human-engineered microvascular networks. This preclinical study introduces a novel PLA prevascularized and implantable construct, along with an array of imaging techniques, to validate the ability of SHED to promote functional human-engineered vessels, further highlighting the interest of SHED for orofacial tissue engineering. Furthermore, this study validates the use of PETscan for the early detection of in vivo angiogenesis, which may be applied in the clinic to monitor the performance of prevascularized grafts. [ABSTRACT FROM AUTHOR] more...

Assessing the possible biological effects of exposure to low doses of ionizing radiation (IR) is one of the prime challenges in radiation protection, especially in medical imaging. Today, radiobiological data on cone beam CT (CBCT) related biological effects are scarce. In children and adults, the induction of DNA double strand breaks (DSBs) in buccal mucosa cells and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) and antioxidant capacity in saliva samples after CBCT examination were examined. No DNA DSBs induction was observed in children nor adults. In children only, an increase in 8-oxo-dG levels was observed 30 minutes after CBCT. At the same time an increase in antioxidant capacity was observed in children, whereas a decrease was observed in adults. Our data indicate that children and adults react differently to IR doses associated with CBCT. Fully understanding these differences could lead to an optimal use of CBCT in different age categories as well as improved radiation protection guidelines. [ABSTRACT FROM AUTHOR] more...

X-linked hypophosphatemia (XLH) is a skeletal disease caused by inactivating mutations in the PHEX gene. Mutated or absent PHEX protein/enzyme leads to a decreased serum phosphate level, which cause mineralization defects in the skeleton and teeth (osteomalacia/odontomalacia). It is not yet altogether clear whether these manifestations are caused solely by insufficient circulating phosphate availability for mineralization or also by a direct, local intrinsic effect caused by impaired PHEX activity. Here, we evaluated the local role of PHEX in a 3-dimensional model of extracellular matrix (ECM) mineralization. Dense collagen hydrogels were seeded either with human dental pulp cells from patients with characterized PHEX mutations or with sex- and age-matched healthy controls and cultured up to 24 d using osteogenic medium with standard phosphate concentration. Calcium quantification, micro-computed tomography, and histology with von Kossa staining for mineral showed significantly lower mineralization in XLH cell-seeded scaffolds, using nonparametric statistical tests. While apatitic mineralization was observed along collagen fibrils by electron microscopy in both groups, Raman microspectrometry indicated that XLH cells harboring the PHEX mutation produced less mineralized scaffolds having impaired mineral quality with less carbonate substitution and lower crystallinity. In the XLH cultures, immunoblotting revealed more abundant osteopontin (OPN), dentin matrix protein 1 (DMP1), and matrix extracellular phosphoglycoprotein (MEPE) than controls, as well as the presence of fragments of these proteins not found in controls, suggesting a role for PHEX in SIBLING protein degradation. Immunohistochemistry revealed altered OPN and DMP1 associated with an increased alkaline phosphatase staining in the XLH cultures. These results are consistent with impaired PHEX activity having local ECM effects in XLH. Future treatments for XLH should target both systemic and local manifestations. [ABSTRACT FROM AUTHOR] more...

X-linked hypophosphatemia (XLH) is a rare genetic skeletal disease where increased phosphate wasting in the kidney leads to hypophosphatemia and prevents normal mineralization of bone and dentin. Here, we examined the periodontal status of 34 adults with XLH and separated them according to the treatment they received for hypophosphatemia. We observed that periodontitis frequency and severity were increased in adults with XLH and that the severity varied according to the hypophosphatemia treatment. Patients who benefited from an early and continuous vitamin D and phosphate supplementation during their childhood presented less periodontal attachment loss than patients with late or incomplete supplementation. Continued hypophosphatemia treatment during adulthood further improved the periodontal health. Extracted teeth from patients with late or incomplete supplementation showed a strong acellular cementum hypoplasia when compared with age-matched healthy controls. These results show that XLH disturbs not only bone and dentin formation but also cementum and that the constitutional defect of the attachment apparatus is associated with attachment loss. [ABSTRACT FROM AUTHOR] more...

Familial hypophosphatemic vitamin D-resistant rickets is a hereditary disease generally transmitted as an X-linked dominant trait and characterized by distinctive general clinical signs. Dental features include spontaneous dental abscesses that occur in the absence of a history of trauma or dental decay. The challenge for the dentist is to prevent and treat these lesions. This report describes the case of a young hypophosphatemic boy with abscesses. In this case, the application of fluid resin composites with a self-etching primer bonding system to all primary teeth prevented abscess formation for more than 1 year and thus avoided endodontic treatment or extraction. This constitutes a new approach to the prevention of spontaneous abscesses on primary teeth in children with familial hypophosphatemic rickets. [ABSTRACT FROM AUTHOR] more...

Background: An International Working Group (IWG) developed new guidelines on the diagnosis, evaluation, management, and monitoring of X-linked hypophosphatemia (XLH) in children. Over the past 5 years, important advances have occurred in our understanding of the presentation, complications and treatment of XLH., Methods: A group of 50 international experts in XLH from Canada, the United States, Europe, Asia and South America, along with methodology experts and patient partners, held 18 teleconference meetings in 2023-2024. These meetings addressed key issues regarding diagnosing, evaluating, managing, and monitoring XLH in children. Two systematic reviews were conducted to examine the impact of burosumab compared to conventional therapy (phosphate salts and active vitamin D) or no therapy, and to assess the impact of conventional therapy versus no therapy on patient-important outcomes. The certainty of evidence was evaluated using the GRADE methodology. Additionally, narrative reviews were completed on XLH diagnosis and the role of genetic testing, and an expert clinical practice survey informed the monitoring recommendations., Outcomes: An approach to establishing the diagnosis of XLH is presented. GRADEd recommendations were developed on treatment strategies for XLH in children. Monitoring recommendations, GRADEd as weak with very low certainty, were based on clinical practice survey of the IWG experts. The guidelines also addressed dental complications and proposed potential strategies to mitigate them., Conclusion: These clinical practice guidelines provide an update of the current evidence on the diagnosis and management of XLH and provide a comprehensive guidance for multidisciplinary healthcare professionals involved in the care of children with XLH., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.) more...

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert. Historically, these patients were treated with frequent doses of oral phosphate supplements and active vitamin D, which was of limited efficiency and associated with adverse effects. However, the management of XLH has evolved in the past few years owing to the availability of burosumab, a fully humanized monoclonal antibody that neutralizes circulating FGF23. Here, we provide updated clinical practice recommendations for the diagnosis and management of XLH to improve outcomes and quality of life in these patients., Competing Interests: Competing interests: J.B. and L.S. receive support for research and consultancy from Kyowa Kirin. A.L., M.B.D., L.R. and C.C. receive research support from Kyowa Kirin. D.H. receives research support and speaker and consultant fees from Kyowa Kirin. The institution of A.L. (AP-HP) receives her speaker and consultant fees from Kyowa Kirin. G.A. receives speaker and consultant fees from Kyowa Kirin. F.E., E.L., P.K., K.B., D.S., M.L.B. and K.B. receive consultation fees from Kyowa Kirin. All other authors declare no competing interests., (© 2025. Springer Nature Limited.) more...