Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis.

Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1+/- mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.

PIN1 is a new therapeutic target of craniosynostosis.

Gain-of-function mutations in fibroblast growth factor receptors (FGFRs) cause congenital skeletal anomalies, including craniosynostosis (CS), which is characterized by the premature closure of craniofacial sutures. Apert syndrome (AS) is one of the severest forms of CS, and the only treatment is surgical expansion of prematurely fused sutures in infants. Previously, we demonstrated that the prolyl isomerase peptidyl-prolyl cis-trans isomerase interacting 1 (PIN1) plays a critical role in mediating FGFR signaling and that Pin1+/- mice exhibit delayed closure of cranial sutures. In this study, using both genetic and pharmacological approaches, we tested whether PIN1 modulation could be used as a therapeutic regimen against AS. In the genetic approach, we crossbred Fgfr2S252W/+, a mouse model of AS, and Pin1+/- mice. Downregulation of Pin1 gene dosage attenuated premature cranial suture closure and other phenotypes of AS in Fgfr2S252W/+ mutant mice. In the pharmacological approach, we intraperitoneally administered juglone, a PIN1 enzyme inhibitor, to pregnant Fgfr2S252W/+ mutant mice and found that this treatment successfully interrupted fetal development of AS phenotypes. Primary cultured osteoblasts from Fgfr2S252W/+ mutant mice expressed high levels of FGFR2 downstream target genes, but this phenotype was attenuated by PIN1 inhibition. Post-translational stabilization and activation of Runt-related transcription factor 2 (RUNX2) in Fgfr2S252W/+ osteoblasts were also attenuated by PIN1 inhibition. Based on these observations, we conclude that PIN1 enzyme activity is important for FGFR2-induced RUNX2 activation and craniofacial suture morphogenesis. Moreover, these findings highlight that juglone or other PIN1 inhibitors represent viable alternatives to surgical intervention for treatment of CS and other hyperostotic diseases.

Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency.

BACKGROUND: The pathophysiology of nonsyndromic craniosynostosis remains poorly understood. The authors seek to understand the cause of this condition with a specific focus on how osteoclasts may contribute to craniosynostosis. Here, the authors characterize proteins differentially expressed in patent and fused cranial sutures by comparing their respective proteomes. METHODS: Fused and patent suture samples were obtained from craniosynostotic patients undergoing surgery at a single academic medical center. Extracted protein from samples was interrogated using mass spectrometry. Differential protein expression was determined using maximum likelihood-based G-test with a q-value cutoffs of 0.5 after correction for multiple hypothesis testing. Immunolocalization of lead protein candidates was performed to validate proteomic findings. In addition, quantitative polymerase chain reaction analysis of corresponding gene expression of proteins of interest was performed. RESULTS: Proteins differentially expressed in patent versus fused sutures included collagen 6A1 (Col6A1), fibromodulin, periostin, aggrecan, adipocyte enhancer-binding protein 1, and osteomodulin (OMD). Maximum likelihood-based G-test suggested that Col6A1, fibromodulin, and adipocyte enhancer-binding protein 1 are highly expressed in patent sutures compared with fused sutures, whereas OMD is up-regulated in fused sutures compared with patent sutures. These results were corroborated by immunohistochemistry. Quantitative polymerase chain reaction data point to an inverse relationship in proteins of interest to RNA transcript levels, in prematurely fused and patent sutures that potentially describes a feedback loop mechanism. CONCLUSIONS: Proteome analysis validated by immunohistochemistry may provide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required.

Stress and displacement patterns in the craniofacial skeleton with rapid maxillary expansion-a finite element method study.

BACKGROUND: Rapid maxillary expansion (RME), indicated in the treatment of maxillary deficiency directs high forces to maxillary basal bone and to other adjacent skeletal bones. The aim of this study is to (i) evaluate stress distribution along craniofacial sutures and (ii) study the displacement of various craniofacial structures with rapid maxillary expansion therapy by using a Finite Element model. METHODS: An analytical model was developed from a dried human skull of a 12 year old male. CT scan images of the skull were taken in axial direction parallel to the F-H plane at 1 mm interval, processed using Mimics software, required portion of the skull was exported into stereo-lithography model. ANSYS software was used to solve the mathematical equation. Contour plots of the displacement and stresses were obtained from the results of the analysis performed. RESULTS: At Node 47005, maximum X-displacement was 5.073 mm corresponding to the incisal edge of the upper central incisor. At Node 3971, maximum negative Y-displacement was -0.86 mm which corresponds to the anterior zygomatic arch, indicating posterior movement of craniofacial complex. At Node 32324, maximum negative Z-displacement was -0.92 mm representing the anterior and deepest convex portion of the nasal septum; indicating downward displacement of structures medial to the area of force application. CONCLUSIONS: Pyramidal displacement of maxilla was evident. Apex of pyramid faced the nasal bone and base was located on the oral side. Posterosuperior part of nasal cavity moved minimally in lateral direction and width of nasal cavity at the floor of the nose increased, there was downward and forward movement of maxilla with a tendency toward posterior rotation. Maximum von Mises stresses were found along midpalatal, pterygomaxillary, nasomaxillary and frontomaxillary sutures.

Genetic advances in craniosynostosis.

Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one in 2,500 live births. In most cases, it occurs as an isolated congenital anomaly, that is, nonsyndromic craniosynostosis (NCS), the genetic, and environmental causes of which remain largely unknown. Recent data suggest that, at least some of the midline NCS cases may be explained by two loci inheritance. In approximately 25-30% of patients, craniosynostosis presents as a feature of a genetic syndrome due to chromosomal defects or mutations in genes within interconnected signaling pathways. The aim of this review is to provide a detailed and comprehensive update on the genetic and environmental factors associated with NCS, integrating the scientific findings achieved during the last decade. Focus on the neurodevelopmental, imaging, and treatment aspects of NCS is also provided.

Comparison and evaluation of stresses generated by rapid maxillary expansion and the implant-supported rapid maxillary expansion on the craniofacial structures using finite element method of stress analysis.

BACKGROUND: The study aimed to evaluate and compare the stress distribution and 3-dimensional displacements along the craniofacial sutures in between the Rapid maxillary Expansion (RME) and Implant supported RME (I-RME). METHODS: Finite element model of the skull and the implants were created using ANSYS software. The finite element model thus built composed of 537692 elements and 115694 nodes in RME model & 543078 elements and 117948 nodes with implants model. The forces were applied on the palatal surface of the posterior teeth to cause 5mm of transverse displacement on either side of the palatal halves, making it a total of 10mm. The stresses and the displacement values were obtained and interpreted. RESULTS: Varying pattern of stress and the displacements with both positive and negative values were seen. The maximum displacement was seen in the case of plain RME model and that too at Pterygomaxillary suture and Mid-palatal suture in descending order. In the case of I-RME maximum displacement was seen at Zygomaticomaxillary suture followed by Pterygomaxillary suture. The displacements produced in all the three planes of space for the plain RME model were greater in comparison to the Implant Supported RME model. And the stresses remained high for all the sutures in case of an I-RME. CONCLUSIONS: There is a definite difference in the stress and the displacement pattern produced by RME and I-RME model and each can be used according to the need of the patient. The stresses generated in case of conventional RME were considerably less than that of the I-RME for all the sutures.

Stress and displacement pattern evaluation using two different palatal expanders in unilateral cleft lip and palate: a three-dimensional finite element analysis.

BACKGROUND: In this finite element (FE) study, the stress distribution and displacement pattern was evaluated in the mid-palatal area and around circum-maxillary sutures exerted by bone-borne palatal expander (BBPE) in comparison with conventional HYRAX rapid palatal expander in unilateral cleft lip and palate. METHODS: Computed tomography scan images of a patient with unilateral cleft palate was used to create a FE model of the maxillary bone along with circum-maxillary sutures. A three-dimensional model of the conventional HYRAX (Hygienic Rapid Expander) expander and custom-made BBPE was created by laser scanning and programmed into the FE model. RESULTS: With the BBPE, the maximum stress was observed at the implant insertion site, whereas with the conventional HYRAX expander, it was at the dentition level. Among the circum-maxillary sutures, the zygomaticomaxillary suture experienced maximum stress followed by the zygomaticotemporal and nasomaxillary sutures. Displacement in the X-axis (transverse) was highest on the cleft side, and in the Y-axis (antero-posterior), it was highest in the posterior region in the BBPE. CONCLUSIONS: The total displacement was observed maximum in the mid-palatal cleft area in the BBPE, and it produced true skeletal expansion at the alveolar level without any dental tipping when compared with the conventional HYRAX expander.

Sutures Possess Strong Regenerative Capacity for Calvarial Bone Injury.

Repair of calvarial bony defects remains challenging for craniofacial surgeons. Injury experiments on animal calvarial bones are widely used to study healing mechanisms and test tissue engineering approaches. Previously, we identified Gli1+ cells within the calvarial sutures as stem cells supporting calvarial bone turnover and injury repair. In this study, we tested the regenerative capacity of the suture region compared with other areas of calvarial bone. Injuries were made to mouse sagittal sutures or other areas of the calvarial bone at varying distances from the suture. Samples were collected at different time points after injury for evaluation. MicroCT and histological analyses were conducted. EdU incorporation analysis was performed to assay cell proliferation. Gli1-CreERT2;Tdtomatoflox mice were used to trace the fate of Gli1+ stem cells after injury. Calvarial sutures possess much stronger regeneration capability than the nonsuture bony areas of the calvaria. The healing rate of the calvarial bone is inversely proportional to the distance between the suture and injury site: injuries closer to the suture heal faster. After complete removal of the sagittal suture, regeneration and restoration of normal organization occur within 6 weeks. Gli1+ cells within the suture mesenchyme are the cellular source for injury repair and bone regeneration. These results demonstrate that calvarial bone healing is not an evenly distributed event on the calvarial surface. Sutures contain stem cells and are the origin of calvarial bone tissue regeneration. Therefore, current practice in calvarial surgery needs to be reevaluated and modified. These findings also necessitate the design of new approaches for repairing calvarial bony defects.

Three-dimensional finite element analysis of maxillary protraction with labiolingual arches and implants.

INTRODUCTION: In this study, we aimed to evaluate the effects of maxillary protraction using traditional labiolingual arches and implant-type protraction devices before orthopedic treatment of patients with skeletal Class III malocclusion. METHODS: A 3-dimensional finite element model of the maxillofacial bones with high biologic similarity and including the sutures was constructed. Through stress and displacement calculations, a biomechanical study was performed for the maxillofacial bones, mandible, and sutures. RESULTS: We quantified detailed changes in the sutures with 2 protraction methods to analyze their effects on the growth of the maxillofacial bones. CONCLUSIONS: (1) The labiolingual arch is suitable for skeletal Class III patients with crossbite and deep overbite. The frontomaxillary and zygomaticomaxillary sutures played major roles in the forward displacement and counterclockwise rotation of the maxilla. The temporozygomatic and pterygopalatine sutures did not change significantly. (2) The implant type of protraction device is suitable for skeletal Class III patients with crossbite and open bite. Both the frontomaxillary and zygomaticomaxillary sutures played decisive roles in the forward displacement and clockwise rotation of maxilla. The temporozygomatic and pterygopalatine sutures showed small changes. (3) The labiolingual arch caused less stimulatory growth on the maxilla, whereas the implant caused greater stimulatory growth on the maxilla. Protraction with the labiolingual arch is more suitable for early skeletal Class III patients at a younger age; protraction with an implant is applicable to skeletal Class III patients in the late mixed dentition or early permanent dentition.

Pancraniosynostosis following endoscopic-assisted strip craniectomy for sagittal suture craniosynostosis in the setting of poor compliance with follow-up: a case report.

INTRODUCTION: There is limited craniofacial literature on the complications of helmet therapy and controversy regarding the effects of inadequate orthotic helmet therapy. The authors present a case of inadvertently prolonged orthotic helmet therapy after endoscopic strip craniectomy for isolated sagittal synostosis. CASE PRESENTATION: A two-month-old Caucasian baby underwent uncomplicated endoscopic-assisted strip craniectomy to treat synostosis of the sagittal suture and was fitted for an orthotic helmet two weeks postoperatively. He presented to the craniofacial clinic eight weeks postoperatively with occipital flattening and increased posterior vault height, so the helmet was refitted. During the next 18 months, the helmet was used inconsistently without follow-up. Upon re-presentation, the patient had developed pansynostosis, requiring a subsequent open total cranial vault reconstruction for correction for this secondary deformity. CONCLUSIONS: Although it remains unclear whether postoperative development of pansynostosis is the result of prolonged helmeting or the consequence of progressive synostotic disease, this report highlights the importance of parent education and judicious scheduled follow-up for the avoidance of potential helmet therapy complications.

Y-craniosynostosis by premature fusion of the metopic and coronal sutures: a new nosological entity or a variety of Saethre-Chotzen syndrome?

BACKGROUND: New forms and varieties of craniosynostoses are continuously identified due to the current increased interest of clinicians and genetists especially since the introduction of microarray-based comparative genomic hybridization (Array-CGH) techniques in the diagnostic setting of patients with craniofacial anomalies. METHODS: In this report, we describe the case of an infant who associated the early fusion of the metopic and both the coronal sutures. The interaction of the early fusion of the anterior group of the main cranial sutures gave the infant a particular clinical phenotypes with a Y configuration of the frontal bone and a globally reduced size of the skull. Such a deformity was observed in utero and was subsequently confirmed by the postnatal imaging of the head. RESULTS: This phenotype was never described previously in antenatal period to our knowledge. The array-CGH showed a heterozygous 9.0 Mb deletion in the chromosomal region 7p21.1p21.3 encompassing approximately 25 other genes, spanning from THSD7A to TWIST1/FERD3L. CONCLUSION: This case further illustrates the variability of the clinical spectrum of craniofacial disorders associated with TWIST1 abnormalities. It is important to note that the Saethre-Chotzen syndrome caused by microdeletion is generally characterized by a mental disability. However, of interest, the postoperative psychomotor development of the child considered hereby was within the normal limits.

Statistical analysis of biomechanical properties of the adult sagittal suture using a bending method in a Japanese forensic sample.

This study examined the mechanical properties of the adult sagittal suture compared with surrounding parietal bones using bending tests and investigated the association between the mechanical properties of the suture and age. We used the heads of 116 Japanese cadavers (76 male cadavers and 40 female cadavers) of known age and sex. A total of 1160 cranial samples, 10 from each skull, were collected. The samples were imaged using multidetector computed tomography, and the sample thickness at the center of each sample (ST) was measured. The failure stress of each sample (FS) was measured by a bending test, and the ratio of failure stress to the square of sample thickness (FS/ST(2)) was calculated. Statistical analyses revealed that the FS and FS/ST(2) values were significantly lower at all suture sites than at all bone sites regardless of sex. There were not significant but slight positive correlations between age and FS and FS/ST(2) values at any suture site in male samples. In female samples, age had significant positive correlations with FS and FS/ST(2) values at the middle suture sites, whereas there were not significant but slight positive correlations between age and FS and FS/ST(2) values at the edges of the suture. Statistical analyses also demonstrated that FS and FS/ST(2) values were significantly greater in male samples than in female samples at the middle suture sites. These findings suggest that the bending strength of the adult sagittal suture is significantly lower than that of surrounding parietal bones. Therefore, avoiding direct impact on cranial sutures may be important for preventing skull fractures and severe complications that can cause death. The results of this study also revealed that the bending strength of the middle sagittal suture significantly increases with age in only female samples, whereas the bending strength is significantly higher in male samples than in female samples at the middle suture sites, indicating the possibility of sex difference in the bony interdigitation of the sutures during childhood.

Pediatric Coronal Suture Fiber Alignment and the Effect of Interdigitation on Coronal Suture Mechanical Properties.

The morphological and mechanical properties of the pediatric skull are important in understanding pediatric head injury biomechanics. Although previous studies have analyzed the morphology of cranial sutures, none has done so in pediatric specimens nor have previous studies related the morphology to mechanical properties of human sutures. This study quantified the geometry of pediatric cranial sutures and investigated its correlation with the suture mechanical properties. First, the suture fiber alignment was quantified using histological analysis for four ages-neonate, 9 months-old, 11 months-old, and 18 months-old. For the morphometric investigation of the suture interdigitation, suture samples from a 6-year-old were scanned using micro-CT and the level of interdigitation was measured using two techniques. The first technique, the sinuosity index, was calculated by dividing the suture path along the surface of the skull by the suture distance from beginning to end. The second technique, the surface area interdigitation index, was calculated by measuring the surface area of the bone interface outlining the suture and dividing it by the cross-sectional area of the bone. The mechanical properties were obtained using methods reported in Davis et al.6. The results of the histological analysis showed a significant increase in fiber alignment in older specimen; where random fiber alignment has an average angle deviation of 45°, neonatal suture fibers have an average deviation of 32.2° and the 18-month-old fibers had an average deviation of 16.2° (p < 0.0001). For the suture index measurements, only the sinuosity was positively correlated with the ultimate strain (R (2) = 0.62, Bonferroni corrected p = 0.011) but no other measurements showed a significant relationship, including the amount of interdigitation and elastic modulus. Our results demonstrate that there is a distinct developmental progression of the suture fiber alignment at a young age, but the differences in suture interdigitation can only predict the ultimate strain and no other mechanical properties.

Effect of St John's wort on bone formation in the orthopaedically expanded premaxillary suture in rats: a histological study.

BACKGROUND/OBJECTIVE: The aim of this study was to investigate the effect of systemic St John's wort (Hypericum perforatum) on bone formation in the expanded premaxillary suture in rats. MATERIALS/METHODS: A total of 28 rats were randomly divided into four groups of equal numbers: control (C); only expansion (OE); St John's wort extract given only during the expansion and retention period (a total of 17 days; SJW group); and St John's wort extract given during the nursery phase before expansion (a period of 40 days), and during the expansion and retention periods (a total of 57 days; N + SJW group). After the 5 day expansion period was completed, the rats in the OE, SJW, and N + SJW groups underwent 12 days of mechanical retention, following which they were killed, and their premaxilla dissected and fixed. Histological examination was performed to determine the number of osteoclasts and capillaries, as well as the number of osteoblasts, inflammatory cell infiltration, and the amount of new bone formation. RESULTS: Statistical analysis showed that the number of osteoclasts and capillaries, and the inflammatory cell infiltration, as well as new bone formation, were higher in the SJW and N + SJW groups than in the other groups. However, statistical analysis demonstrated that among these two groups, all parameters, with the exception of the number of capillaries, were higher in the N + SJW group than the SJW group. CONCLUSIONS/IMPLICATIONS: Although more effective in long-term usage, systemic use of St John's wort hastens new bone regeneration at the premaxillary suture and may help prevent relapse after expansion.

The effects of micro-implant assisted rapid palatal expansion (MARPE) on the nasomaxillary complex--a finite element method (FEM) analysis.

BACKGROUND: Orthodontic palatal expansion appliances have been widely used with satisfactory and, most often, predictable clinical results. Recently, clinicians have successfully utilized micro-implants with palatal expander designs to work as anchors to the palate to achieve more efficient skeletal expansion and to decrease undesired dental effects. The purpose of the study was to use finite element method (FEM) to determine the stress distribution and displacement within the craniofacial complex when simulated conventional and micro-implant-assisted rapid palatal expansion (MARPE) expansion forces are applied to the maxilla. The simulated stress distribution produced within the palate and maxillary buttresses in addition to the displacement and rotation of the maxilla could then be analyzed to determine if micro-implants aid in skeletal expansion. METHODS: A three-dimensional (3D) mesh model of the cranium with associated maxillary sutures was developed using computed tomography (CT) images and Mimics modeling software. To compare transverse expansion stresses in rapid palatal expansion (RPE) and MARPE, expansion forces were distributed to differing points on the maxilla and evaluated with ANSYS simulation software. RESULTS: The stresses distributed from forces applied to the maxillary teeth are distributed mainly along the trajectories of the three maxillary buttresses. In comparison, the MARPE showed tension and compression directed to the palate, while showing less rotation, and tipping of the maxillary complex. In addition, the conventional hyrax displayed a rotation of the maxilla around the teeth as opposed to the midpalatal suture of the MARPE. This data suggests that the MARPE causes the maxilla to bend laterally, while preventing unwanted rotation of the complex. CONCLUSIONS: In conclusion, the MARPE may be beneficial for hyperdivergent patients, or those that have already experienced closure of the midpalatal suture, who require palatal expansion and would worsen from buccal tipping of the teeth or maxillary complex.

Isolated frontosphenoidal synostosis: a rare cause of synostotic frontal plagiocephaly.

OBJECT: Unilateral fusion of the frontoparietal suture is the most common cause of synostotic frontal plagiocephaly. Localized fusion of the frontosphenoidal suture is rare but can lead to a similar, but subtly distinct, phenotype. METHODS: A retrospective chart review of the authors' craniofacial database was performed. Patients with isolated frontosphenoidal synostosis on CT imaging were included. Demographic data, as well as the clinical and radiographic findings, were recorded. RESULTS: Three patients were identified. All patients were female and none had an identifiable syndrome. Head circumference was normal in each patient. The mean age at presentation was 4.8 months (range 2.0-9.8 months); 2 fusions were on the right side. Frontal flattening and recession of the supraorbital rim on the fused side were consistent physical findings. No patient had appreciable facial angulation or orbital dystopia, and 2 patients had anterior displacement of the ipsilateral ear. All 3 patients were initially misdiagnosed with unilateral coronal synostosis, and CT imaging at a mean age of 5.4 months (range 2.1-10.8 months) was required to secure the correct diagnosis. Computed tomography findings included patency of the frontoparietal suture, minor to no anterior cranial base angulation, and vertical flattening of the orbit without sphenoid wing elevation on the fused side. One patient underwent CT scanning at 2.1 months of age, which demonstrated a narrow, but patent, frontosphenoidal suture. The patient's condition was assumed to be a deformational process, and she underwent 6 months of unsuccessful helmet therapy. A repeat CT scan obtained at 10.7 months of age demonstrated the synostosis. All 3 patients underwent fronto-orbital correction at mean age of 12.1 months (range 7.8-16.1 months). The mean duration of postoperative follow-up was 11.7 months (range 1.9-23.9 months). CONCLUSIONS: Isolated frontosphenoidal synostosis should be considered in the differential diagnosis of atypical frontal plagiocephaly.

Finite element analysis of bone stress after SARPE.

PURPOSE: This study investigated stress distribution in maxillas that underwent surgically assisted palatal expansion (SARPE). MATERIALS AND METHODS: Five maxillary models were built: no osteotomy (M1), Le Fort I osteotomy with a step in the zygomaticomaxillary buttress (M2), Le Fort I osteotomy with a step in the zygomaticomaxillary buttress and the pterygomaxillary disjunction (M3), Le Fort I osteotomy without a step (M4), and Le Fort I osteotomy with pterygomaxillary disjunction and no step (M5). Displacement coherence and maximum stress (MS) analyses were used for all models. RESULTS: Areas of tension spread to the maxilla and the region between the alveolar ridge and the palate and a critical point in the median suture for M2, M3, M4, and M5. In M2 and M4, MS spread farther toward and over the pterygoid process, contrary to what was found in M3 and M5. M3 had a better performance than the other models, and the tensile stress was interrupted by the posterior osteotomy, thus avoiding possible damage to the sphenoid bone or difficulties in expanding the posterior region of the maxilla. CONCLUSIONS: The steps in the zygomaticomaxillary buttress and the pterygomaxillary disjunction seem to be important to decrease the harmful dissipation of tensions during SARPE.

Absence of endochondral ossification and craniosynostosis in posterior frontal cranial sutures of Axin2(-/-) mice.

During the first month of life, the murine posterior-frontal suture (PF) of the cranial vault closes through endochondral ossification, while other sutures remain patent. These processes are tightly regulated by canonical Wnt signaling. Low levels of active canonical Wnt signaling enable endochondral ossification and therefore PF-suture closure, whereas constitutive activation of canonical Wnt causes PF-suture patency. We therefore sought to test this concept with a knockout mouse model. PF-sutures of Axin2(-/-) mice, which resemble a state of constantly activated canonical Wnt signaling, were investigated during the physiological time course of PF-suture closure and compared in detail with wild type littermates. Histological analysis revealed that the architecture in Axin2(-/-) PF-sutures was significantly altered in comparison to wild type. The distance between the endocranial layers was dramatically increased and suture closure was significantly delayed. Moreover, physiological endochondral ossification did not occur, rather an ectopic cartilage appeared between the endocranial and ectocranial bone layers at P7 which eventually involutes at P13. Quantitative PCR analysis showed the lack of Col10α1 upregulation in Axin2(-/-) PF-suture. Immunohistochemistry and gene expression analysis also revealed high levels of type II collagen as compared to type I collagen and absence of Mmp-9 in the cartilage of Axin2(-/-) PF-suture. Moreover, TUNEL staining showed a high percentage of apoptotic chondrocytes in Axin2(-/-) PF-sutures at P9 and P11 as compared to wild type. These data indicated that Axin2(-/-) PF-sutures lack physiological endochondral ossification, contain ectopic cartilage and display delayed suture closure.

Técnica con arcos botantes para la abertura de la sutura occipitomastoidea / Using the structural buttresses of the skull to open the occipitomastoid suture

El agujero rasgado posterior es una zona clave en el tratamiento craneal osteopático, pues nos permite actuar sobre el importante paquete vasculonervioso que lo atraviesa. Las técnicas estructurales de articulación se utilizan para liberar las suturas y devolver la movilidad a las fibras óseas e intersuturales en disfunción. El objetivo de la Técnica con arcos botantes para la sutura occipitomastoidea es mejorar la elasticidad ósea para desimbricar la sutura descomprimiéndola, y liberar el agujero rasgado posterior y su contenido. Son indispensables una buena evaluación diagnóstica, el conocimiento de los beneficios y riesgos, y una correcta ejecución, para recuperar la movilidad del la sutura y los huesos occipital y temporal, consiguiendo de este modo, mejorar la sintomatología (AU)

The jugular foramen is key to atypical cranial osteopathy treatment as it allows us to act on the vasculonervous bundle that passes through it. Structural articulatory techniques were used to open the sutures and restore mobility to the dysfunctioning intersutural and bone fibers. The objective of using the structural buttresses technique to open the occipitomastoid suture is to improve bone elasticity to open the decompresed suture and to release the jugular foramen and the elements its contains. A good diagnostic assessment, awareness of the benefits and risks and correct employment of the technique are essential to restore mobility to the suture and the occipital and temporal bones, thereby improving the symtomatology (AU)

Changes in biomechanical strain and morphology of rat calvarial sutures and bone after Tgf-ß3 inhibition of posterior interfrontal suture fusion.

Craniofacial sutures are bone growth fronts that respond and adapt to biomechanical environments. Little is known of the role sutures play in regulating the skull biomechanical environment during patency and fusion conditions, especially how delayed or premature suture fusion will impact skull biomechanics. Tgf-ß3 has been shown to prevent or delay suture fusion over the short term in rat skulls, yet the long-term patency or its consequences in treated sutures is not known. It was therefore hypothesized that Tgf-ß3 had a long-term impact to prevent suture fusion and thus alter the skull biomechanics. In this study, collagen gels containing 3 ng Tgf-ß3 were surgically placed superficial to the posterior interfrontal suture (IFS) and deep to the periosteum in postnatal day 9 (P9) rats. At P9, P24, and P70, biting forces and strains over left parietal bone, posterior IFS, and sagittal suture were measured with masticatory muscles bilaterally stimulated, after which the rats were sacrificed and suture patency analyzed histologically. Results demonstrated that Tgf-ß3 treated sutures showed less fusion over time than control groups, and strain patterns in the skulls of the Tgf-ß3-treated group were different from that of the control group. Although bite force increased with age, no alterations in bite force were attributable to Tgf-ß3 treatment. These findings suggest that the continued presence of patent sutures can affect strain patterns, perhaps when higher bite forces are present as in adult animals.