Search Results (160)

Aim: Pacifiers play a critical role in the early stages of craniofacial and palate development during infancy. While they provide comfort and aid in soothing, their use can also have significant impacts on the growth and function of the oral cavity. This study aimed to simulate and predict the behavior of six different types of pacifiers and their functional interaction with the tongue and palate, with the goal of understanding their potential effects on orofacial growth and development. Materials and Methods: Biomechanical analysis using Finite Element Analysis (FEA) mathematical models was employed to evaluate the behavior of six different commercial pacifiers in contact with the palate and tongue. Three-dimensional solid models of the palate and tongue were based on the mathematical framework from a 2007 publication. This allowed for a detailed investigation into how various pacifier designs interact with soft and hard oral tissues, particularly the implications on dental and skeletal development. Results: The findings of this study demonstrate that pacifiers exhibit different interactions with the oral cavity depending on their geometry. Anatomical–functional pacifiers, for instance, tend to exert lateral compressions near the palatine vault, which can influence the hard palate and contribute to changes in craniofacial growth. In contrast, other pacifiers apply compressive forces primarily in the anterior region of the palate, particularly in the premaxilla area. Furthermore, the deformation of the tongue varied significantly across different pacifier types: while some pacifiers caused the tongue to flatten, others allowed it to adapt more favorably by assuming a concave shape. These variations highlight the importance of selecting a pacifier that aligns with the natural development of both soft and hard oral tissues. Conclusions: The results of this study underscore the crucial role of pacifier geometry in shaping both the palate and the tongue. These findings suggest that pacifiers have a significant influence not only on facial bone growth but also on the stimulation of oral functions such as suction and feeding. The geometry of the pacifier affects the soft tissues (tongue and muscles) and hard tissues (palate and jaw) differently, which emphasizes the need for careful selection of pacifiers during infancy. Choosing the right pacifier is essential to avoid potential negative effects on craniofacial development and to ensure that the benefits of proper oral function are maintained. Therefore, healthcare professionals and parents should consider these biomechanical factors when introducing pacifiers to newborns. Full article

Background/Objectives: Anterior dental trauma in adolescents presents complex restorative challenges due to ongoing craniofacial development and high aesthetic expectations. This study evaluated the long-term clinical performance of feldspathic ceramic veneers and lithium disilicate crowns used in the anterior region following dental trauma in adolescents. Methods: A total of 209 restorations were placed in 85 adolescents (50 females, 35 males), aged 11.1–17.9 years (mean age: 15.1 years). Of these, 144 were lithium disilicate crowns, and 65 were feldspathic ceramic veneers. All restorations were fabricated using minimally invasive protocols and followed up for periods ranging from 3 to 60 months. Outcomes were assessed based on standardized clinical criteria for success and failure. Results: Lithium disilicate crowns exhibited superior long-term performance, with the majority of failures occurring in feldspathic veneers (p < 0.001), primarily due to chipping or structural fracture. Age and gender had no statistically significant influence on failure rates. Conclusions: Both feldspathic and lithium disilicate ceramic restorations represent viable treatment options for anterior dental trauma in adolescents. However, lithium disilicate demonstrates greater mechanical reliability, particularly in teeth with significant hard tissue loss. These results support the use of durable ceramic materials in adolescent restorative protocols involving dental trauma. Full article

Craniofacial development is a complex, highly conserved process involving multiple tissue types and molecular pathways, with perturbations resulting in congenital defects that often require invasive surgical interventions to correct. Remarkably, some species, such as Xenopus laevis, can correct some craniofacial abnormalities during pre-metamorphic stages through thyroid hormone-independent mechanisms. However, the full scope of factors mediating remodeling initiation and coordination remain unclear. This study explores the differential remodeling responses of craniofacial defects by comparing the effects of two pharmacological agents, thioridazine-hydrochloride (thio) and ivermectin (IVM), on craniofacial morphology in X. laevis. Thio-exposure reliably induces a craniofacial defect that can remodel in pre-metamorphic animals, while IVM induces a permanent, non-correcting phenotype. We examined developmental changes from feeding stages to hindlimb bud stages and mapped the effects of each agent on the patterning of craniofacial tissue types including: cartilage, muscle, and nerves. Our findings reveal that thio-induced craniofacial defects exhibit significant consistent remodeling, particularly in muscle, with gene expression analysis revealing upregulation of key remodeling genes, matrix metalloproteinases 1 and 13, as well as their regulator, prolactin.2. In contrast, IVM-induced defects show no significant remodeling, highlighting the importance of specific molecular and cellular factors in pre-metamorphic craniofacial correction. Additionally, unique neuronal profiles suggest a previously underappreciated role for the nervous system in tissue remodeling. This study provides novel insights into the molecular and cellular mechanisms underlying craniofacial defect remodeling and lays the groundwork for future investigations into tissue repair in vertebrates. Full article

Background/Objectives: Temporomandibular disorders (TMDs) are a group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and related anatomical structures. Although magnetic resonance imaging (MRI) is considered a noninvasive and highly informative imaging modality for assessing TMJ soft tissues, few studies have examined how TMJ structural features observed on MRI findings relate to oral function and craniofacial morphology in female patients with malocclusion. To investigate the associations among TMJ structural features, oral function, and craniofacial morphology in female patients with malocclusion, using MRI findings interpreted in conjunction with a preliminary assessment based on selected components of the DC/TMDs Axis I protocol. Methods: A total of 120 female patients (mean age: 27.3 ± 10.9 years) underwent clinical examination based on DC/TMDs Axis I and MRI-based structural characterization of the TMJ. Based on the structural features identified by MRI, patients were classified into four groups for comparison: osteoarthritis (OA), bilateral disk displacement (BDD), unilateral disk displacement (UDD), and a group with Osseous Change/Disk Displacement negative (OC/DD (−)). Occlusal contact area, occlusal force, masticatory efficiency, tongue pressure, and lip pressure were measured. Lateral cephalometric analysis assessed skeletal and dental patterns. Results: OA group exhibited significantly reduced occlusal contact area (p < 0.0083, η² = 0.12) and occlusal force (p < 0.0083, η² = 0.14) compared to the OC/DD (−) group. Cephalometric analysis revealed that both OA and BDD groups had significantly larger ANB angles (OA: 5.7°, BDD: 5.2°, OC/DD (−): 3.7°; p < 0.0083, η² = 0.21) and FMA angles (OA: 32.4°, BDD: 31.8°, OC/DD (−): 29.0°; p < 0.0083, η² = 0.17) compared to the OC/DD (−) group. No significant differences were observed in masticatory efficiency, tongue pressure, or lip pressure. Conclusions: TMJ structural abnormalities detected via MRI, especially osteoarthritis, are associated with diminished oral function and skeletal Class II and high-angle features in female patients with malocclusion. Although orthodontic treatment is not intended to manage TMDs, MRI-based structural characterization—when clinically appropriate—may aid in treatment planning by identifying underlying joint conditions. Full article

Background/Objectives: Craniofacial microsomia (CFM), previously known as hemifacial microsomia, is a congenital condition involving structures derived from the first and second pharyngeal arches. CFM is characterized by asymmetrical craniofacial growth, affecting the mandible, ear, orbit, soft tissues, and facial nerve. Functional therapy is among the treatment options for mild to moderate cases. This study aimed to assess the effect of functional therapy on mandibular growth in patients with CFM by comparing mandibular and condylar height on the affected and unaffected sides, using pre- and post-treatment panoramic radiographs. Methods: A retrospective longitudinal study was conducted on 14 patients treated with functional therapy with the Asymmetrical Functional Activator (AFA) appliance. Mandibular ramus height (Co-Go) and condylar height (Co-Is) were measured bilaterally on pre- (T0) and post-treatment (T1) panoramic radiographs. Growth differences and rates were analyzed using descriptive and inferential statistics. Results: A significant increase in the mandibular ramus height (Co-Go) and in condylar height (Co-Is) was observed on the affected side from T0 to T1. The increase in mandibular ramus height was significantly greater on the affected side compared to the unaffected side (p = 0.0016). Although condylar height increased significantly on both sides over time, the difference in growth rate between sides was not statistically significant (p = 0.7148). Conclusions: Functional therapy may contribute to reducing mandibular asymmetry in CFM patients by enhancing the growth of the affected mandibular ramus, but the asymmetry may still be present at the end of treatment. These findings support its use in the early management of mild to moderate CFM. Full article

Background/Objectives: Chronic craniofacial inflammation is recognized as a factor in anxiety-like behaviors, yet effective therapeutic options remain limited. Agmatine, a dietary bioactive compound found in fermented foods such as sake lees, exhibits modulatory effects on neural functions, alleviating psychological distress like anxiety associated with local inflammation. Methods: We investigated both the therapeutic and preventive effects of agmatine on anxiety-like behaviors and the related neural basis in a mouse model of persistent craniofacial inflammation induced by complete Freund’s adjuvant (CFA). Results: Comprehensive behavioral assessments, including the elevated plus maze, open field, dark–light box, social interaction, and novel object recognition tests, revealed that therapeutic agmatine administration (1.0 and 30 mg/kg) significantly reduced CFA-induced anxiety-like behaviors, with the higher dose showing more robust and sustained effects across multiple time points. These behavioral improvements were paralleled by reductions in acetylated histone H3, FosB, and c-Fos expression in key anxiety-related brain regions, suggesting a reversal of craniofacial inflammation-associated neural changes. In contrast, preventive agmatine treatment exerted modest and time-dependent behavioral benefits with minimal molecular normalization. Notably, preventive agmatine did not affect general locomotor activity (indicated by total movement distance), indicating that its anxiolytic effects were not confounded by altered locomotor activity. Metabolomic analysis confirmed the presence of agmatine in sake lees (~0.37 mM), supporting the hypothesis that fermented food products might offer dietary routes to emotional resilience. Conclusions: These findings underscore agmatine’s promise as a context-specific epigenetic modulator capable of mitigating anxiety-like behaviors by normalizing inflammation-driven molecular dysregulation in the brain. Full article

Aim: This systematic review aims to evaluate the use of mesenchymal stem cells, particularly those derived from bone marrow, adipose tissue, and dental pulp in maxillofacial and oral surgery, focusing on their regenerative potential, clinical applications, and integration with biomaterials. Introduction: Mesenchymal stem cells are multipotent stem cells known for their immunomodulatory and regenerative abilities. Their low immunogenicity and differentiation capacity make them ideal for treating craniofacial defects and enhancing soft tissue repair. Materials and Methods: The review followed PRISMA guidelines and was registered in PROSPERO. The literature was searched across PubMed, Scopus, and Web of Science from 2009 to 2024. Twelve studies met the inclusion criteria and were analyzed for clinical efficacy and methodological quality. Results: Clinical trials demonstrated the safety and regenerative benefits of mesenchymal stem cell in bone and soft tissue reconstruction. Adipose-derived stem cell and dental pulp stem cell showed favorable outcomes in angiogenesis and healing, while bone marrow’s cell proved effective in bone regeneration, particularly when combined with scaffolds. Discussion and Conclusions: Although results are promising, limitations remain in consistency and long-term outcomes. Optimizing scaffold integration, preservation methods, and delivery techniques is crucial. Mesenchymal stem cell-based therapies represent a powerful, minimally invasive alternative to traditional grafting in oral and maxillofacial surgery. Full article

The Arhgap29 gene encodes Rho-GTPase-activating protein 29 (Arhgap29), which plays a crucial role in embryonic tissue development. Mutations in the Arhgap29 gene are significantly associated with non-syndromic cleft lip and palate (NSCL/P). Our study demonstrated that the deletion of Arhgap29 leads to syndromic cleft lip and palate (SCL/P) characteristics in mice, where, in addition to cleft palate, the mice exhibit craniofacial and systemic skeletal abnormalities. However, the mechanisms underlying these skeletal abnormalities remain unclear. Through micro-CT imaging, histological analysis, and transcriptomic methods, we discovered that the knockout of Arhgap29 delays the fusion of Meckel’s cartilage, widens cranial sutures, reduces bone quality, and alters the expression of osteoblasts and osteoclasts in the mandible. Digit defects, including ectrodactyly and impaired endochondral ossification, were also observed. Immunohistochemical analysis demonstrated the expression of Arhgap29 in both osteoblasts and osteoclasts, indicating its dual role in maintaining matrix homeostasis and regulating bone resorption equilibrium. Transcriptomic analysis revealed disrupted calcium and MAPK signaling pathways, while in vitro studies demonstrated impaired osteogenesis in Arhgap29-deficient calvarial cells, mirroring the in vivo defects. Furthermore, spatial transcriptomics linked the loss of Arhgap29 to defective bone differentiation and protein synthesis. Our findings underscore the critical role of Arhgap29 in the development of the mandible and digits, suggesting its potential as a pathogenic gene associated with syndromic cleft lip and palate (SCL/P). Full article

Understanding how intricate cellular networks and signaling pathways communicate during the formation of craniofacial tissues like the palate and tooth has been the subject of intense investigation for several decades. Both organ systems undergo patterning morphogenesis and the subsequent terminal differentiation of matrix-producing cells that form biomineralized matrices like bone, enamel, dentin, and cementum. Until recently, gene expression profiles could only be assessed for a select number of cells without the context of the entire milieu of genes expressed by neighboring cells and tissues. Today, the cutting-edge field of spatial transcriptomics offers a remarkable suite of innovative technologies of multiplex gene analyses and imaging that can assess the expression of a vast library of genes that are present in situ during normal and abnormal conditions. In this review, we summarize some key technologies which have in recent years enabled an unprecedented breadth and depth of transcriptomic analyses in craniofacial development. We focus in detail on select methods that our research group has applied to better understand the cellular and molecular events that drive palate and tooth development. Our overall goal is to unravel the complexities of these unique biological systems to provide meaningful biological insights into the cellular and molecular events that drive normal development. As a work-in-progress, we strive for a deeper understanding of the temporal and spatial gene expression profiles within cells and tissues during normal and abnormal palate and tooth development. Such knowledge provides the framework for further studies that can characterize the function of new or novel genes that have the potential of serving as therapeutic targets for correcting disorders like cleft palate and tooth agenesis. Full article

Squid skin decellularized dermal matrix (SADM) is gaining attention in tissue engineering and regenerative medicine due to its mimicking of the extracellular matrix property. Hence, SADM was used to investigate mimicking the microenvironment of cellular growth, inducing cellular infiltration and angiogenesis, and facilitating the repair of acute craniofacial wounds. For this, tissue regeneration membranes from squid skin were prepared by decolorization, degreasing and decellularisation methods. The effect of SADM in guiding bone tissue regeneration was evaluated using the rabbit skull bone defect model. SEM images of SADM had a bilayer membrane architecture characterized by a reticulated porous structure on one side and a dense, non-porous surface on the opposite side. Notably, the water absorption capacity of SADM was approximately eight times higher than its weight, exhibiting a porosity of 58% and a peak average tensile stress of 10.43 MPa. Additionally, simulations of tissue fluid degradation indicated a degradation rate of 70.42% and 88.33% on days 8 and 12, respectively. Following 4 and 8 weeks of animal studies focused on repairing cranial bone defects in rabbits, the findings demonstrated that SADM served as an effective barrier against fibrous connective tissue, promoted the proliferation of osteoblasts, and supported bone regeneration. This was confirmed through micro-CT imaging, and sections were stained with senna solid green. In summary, SADM is capable of directing cell infiltration and bone tissue formation, modulating the expression and secretion of inflammatory and skin repair-related factors, thereby enhancing tissue healing. Full article

Background: Craniofacial malformations lie at the heart of fetal alcohol spectrum disorders (FASDs). While there is growing evidence for a genetic component in FASDs, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. The bone morphogenetic protein (Bmp) signaling pathway-dependent endoderm pouch formation is a key mechanism in facial development. We have previously shown that multiple Bmp mutants are sensitized to ethanol-induced facial defects. However, ethanol does not directly impact Bmp signaling. This suggests that downstream effectors, like nkx2.3, may mediate the impact of ethanol on Bmp mutants. Methods: We use an ethanol exposure paradigm with nkx2.3 knockdown approaches to test if nkx2.3 loss sensitizes Bmp mutants to ethanol-induced facial defects. We combine morphometric approaches with immunofluorescence and a hybridization chain reaction to examine the cellular mechanisms underlying Bmp–ethanol interactions. Results: We show that Bmp–ethanol interactions alter the morphology of the endodermal pouches, independent of nkx2.3 gene expression. Knockdown of nkx2.3 does not sensitize wild-type or Bmp mutants to ethanol-induced facial defects. However, we did observe a significant increase in CNCC apoptosis in ethanol-treated Bmp mutants, suggesting an ethanol sensitive, Bmp-dependent signaling pathway driving tissue interactions at the heart of FASDs. Conclusions: Collectively, our work builds on the mechanistic understanding of ethanol-sensitive genes and lays the groundwork for complex multi-tissue signaling events that have yet to be explored. Ultimately, our work provides a mechanistic paradigm of ethanol-induced facial defects and connects ethanol exposure with complex tissue signaling events that drive development. Full article

Background: Childhood obesity and overweight conditions impact systemic health and craniofacial development. Objectives: This review assessed the influence of elevated body mass index (BMI) on craniofacial morphology, considering age, sex, and ethnicity. Methods: A comprehensive search of Scopus, Web of Science, Embase, Cochrane, PubMed, and OpenGrey was conducted following PRISMA guidelines. Ten cross-sectional studies involving 1383 individuals aged 6 to 18 years were included. The sample comprised 812 females and 571 males, with most studies focusing on adolescents aged 12–18 years of different ethnicities depending on the study. Craniofacial structures were compared between overweight/obese and normal weight groups through cephalometric analysis. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). Results: Overweight and obese individuals showed significant craniofacial changes, including increased anterior cranial base length, maxillary and mandibular dimensions, bimaxillary prognathism, and greater soft tissue thickness. These alterations may be influenced by differences in tissue composition, hormonal fluctuations, fat-to-bone ratio, and metabolic disorders. Variations in skeletal divergence, dental alignment, and airway space were also observed. The methodological quality ranged from moderate to high. Conclusions: Excess weight during growth is linked to distinct craniofacial alterations. Orthodontic diagnostics should integrate metabolic and hormonal considerations to optimize treatment outcomes. These changes should be carefully considered by orthodontists and pediatric dentists. Longitudinal studies are needed to understand the long-term effects of obesity on craniofacial development. Full article

Background/Objectives: In contrast to endochondral bone healing, the process of intramembranous bone regeneration is poorly understood. This limits our ability to repair and regenerate the craniofacial skeleton to either correct deformity or optimally heal tissues following injury. While there are several preclinical models of intramembranous regeneration within the craniofacial skeleton, some are not load bearing and others are technically challenging. The goal of this pilot study is therefore to describe a simple method for induction of cortical defects within the mandible that does not involve compounding injury to the surrounding tissues. Methods: Single cortex defects were generated in the mandible body of 8-week-old male and female mice. The extent of bone regeneration within the defect was characterized at days 0, 3, 14, and 28 following defect generation via micro-computed tomography and histology. Conclusions: Observed healing was predictable and reproducible and resulted in intramembranous bone formation. This model will help aid the understanding of intramembranous bone healing in load bearing bones (e.g., mandible) within the craniofacial skeleton Full article

Background: The characterization of facial sexual dimorphic patterns in healthy populations serves as valuable normative data to tailor functionally effective surgical treatments and predict their aesthetic outcomes and to identify dysmorphic facial traits related to hormonal disorders and genetic syndromes. Although the analysis of facial sexual differences in juveniles of different ages has already been investigated, few studies have approached this topic with three-dimensional (3D) geometric morphometric (GMM) analysis, whose interpretation may add important clinical insight to the current understanding. This study aims to investigate the location and extent of facial sexual variations in juveniles through a spatially dense GMM analysis. Methods: We investigated 3D stereophotogrammetric facial scans of 304 healthy Italians aged 3 to 18 years old (149 males, 155 females) and categorized into four different age groups: early childhood (3–6 years), late childhood (7–12 years), puberty (13–15 years), and adolescence (16–18 years). Geometric morphometric analyses of facial shape (allometry, general Procrustes analysis, Principal Component Analysis, Procrustes distance, and Partial Least Square Regression) were conducted to detail sexually dimorphic traits in each age group. Results: The findings confirmed that males have larger faces than females of the same age, and significant differences in facial shape between the two sexes exist in all age groups. Juveniles start to express sexual dimorphism from 3 years, even though biological sex becomes a predictor of facial soft tissue morphology from the 7th year of life, with males displaying more protrusive medial facial features and females showing more outwardly placed cheeks and eyes. Conclusions: We provided a detailed characterization of facial change trajectories in the two sexes along four age classes, and the provided data can be valuable for several clinical disciplines dealing with the craniofacial region. Our results may serve as comparative data in the early diagnosis of craniofacial abnormalities and alterations, as a reference in the planning of personalized surgical and orthodontic treatments and their outcomes evaluation, as well as in several forensic applications such as the prediction of the face of missing juveniles. Full article

Background/Objectives: Facial soft tissue thickness (FSTT) data are extensively utilized in forensic and medical sciences, serving as a foundational element for craniofacial reconstruction and identification methods. This study aims to analyze the differences in FSTT measurements between upright and supine positions in living subjects. Methods: The study sample consisted of 121 participants aged 20 to 86 years from Slovakia. Biological sex and age data were collected. FSTT measurements were taken at eight medial facial line landmarks and eight bilateral landmarks using a non-invasive General Electric LOGIQe R7 ultrasound device. Results: The results indicate that the head position significantly influenced more than half of the landmarks, with mean differences not exceeding 1.31 mm. Most FSTT values were higher in the horizontal position. Younger males and females exhibited significant differences in FSTT across various regions, including the eye, cheek, nose and mouth, with discrepancies in the forehead, chin, and cheek regions among younger males. In older males, only the gonion region showed a significant position-related difference, while older females demonstrated substantial FSTT changes at five landmarks, with the largest difference (1.31 mm) observed at the mandible, accounting for 15.74% of the mean FSTT. Compared to younger groups, older females exhibited higher FSTT values in the upright position. Conclusions: These findings suggest that measurements in an upright position may be more suitable for facial reconstruction, as positional changes in FSTT can occur in both positive and negative directions. Full article