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.

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.

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.

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.

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.

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.

Deficient language acquisition in children with single suture craniosynostosis and deformational posterior plagiocephaly.

PURPOSE: This study examined early language acquisition in children with single suture craniosynostosis (SSC) and in children with deformational posterior plagiocephaly. Our purpose was to determine whether infants with SSC have normal language acquisition at the age of 3 years, and whether infants with deformational posterior plagiocephaly demonstrate parallel development when compared with children with SSC. METHODS: The study population includes 61 infants. Twenty of them had synostosis of the sagittal suture, 12 synostosis of other suture and 29 deformational posterior plagiocephaly. Forty-nine of them were operated on a mean age of 10.6 months, and 12 were non-operated children with deformational posterior plagiocephaly. Language skills of participants were prospectively evaluated at the mean age of 3 years 4 months. RESULTS: About one half of the subjects (49%) had normal linguistic development, 30% had slight developmental problems and 21% had severe disorders in speech-language-related skills. These figures showed the prevalence of severe language disorders to be three times higher in our study population when compared with the general population. Children with sagittal synostosis managed better in all language skills compared with other types of SSC. Defective language development was found in deformational posterior plagiocephaly, both operated and non-operated. CONCLUSIONS: We found a noticeable developmental risk for specific language impairment in children with nonsyndromic SSC, and that the deviant language development is observable already in early infancy. Contrary to previous beliefs, the developmental risk for defective language development in deformational posterior plagiocephaly was found in both operated and non-operated subjects.

Spring expansion is influenced by cranial biomechanics.

INTRODUCTION: Spring cranioplasty is used in selected cases of craniosynostosis. A rabbit model was used to determine (1) if cranial biomechanics modify the expected rate of spring expansion, (2) the residual spring force in situ after cranial expansion, and (3) if the spring weakens during clinical use. MATERIALS AND METHODS: Twenty-seven New Zealand white rabbits were divided into 3 groups: the treatment group that underwent posterior frontal suturectomy and spring expansion (n = 15) and the control (n = 6) and sham groups (n = 6) that underwent suturectomy and incision only, respectively. Cephalography measured cranial expansion for 7 weeks. Spring force-deflection curves were measured in a dynamometer before and after use. RESULTS: Significant cranial expansion was observed for 8 hours (15% of the total expansion). The rate of expansion decreased significantly between 48 and 96 hours followed by a second period of rapid expansion from 96 hours to 7 days (P = 0.001). Approximately 80% of expansion was achieved by 2 weeks and 90% by 3 weeks. Initial spring force was 9.4 N (range, 7.2-10.7). Once the spring had achieved 90% of its eventual expansion, it retained 40% of its original force. At the completion of cranial expansion, the residual spring force was 2.6 N (range, 1.4-4.0) or 28% of the original spring force. All springs maintained identical load-compression curves after use. CONCLUSIONS: The craniofacial structures are mechanically complex and modify the uniform expansion curve expected as the spring force decays. Significant force is maintained within the spring at the completion of cranial expansion. This may have implications for possible relapse if the springs are removed early.

Modifications of midpalatal sutural density induced by rapid maxillary expansion: A low-dose computed-tomography evaluation.

INTRODUCTION: The aim of this study was to evaluate the density of the midpalatal suture as assessed by low-dose computed tomography (CT) before rapid maxillary expansion (RME) (T0), at the end of active expansion (T1), and after a retention period of 6 months (T2). METHODS: The study sample comprised 17 prepubertal subjects (mean age, 11.2 years) with constricted maxillary arches and unilateral or bilateral posterior crossbite. The total amount of expansion was 7 mm in all subjects. Multi-slice low-dose CT scans were taken at T0, T1, and T2. On axial CT scanned images, 4 regions of interest (ROIs) were placed along the midpalatal suture (anterior [AS ROI] and posterior [PS ROI]) and in 2 regions of palatal bone (anterior and posterior). Density was measured in Hounsfield units. The Mann-Whitney U test and Friedman analysis of variance (ANOVA) with post-hoc test were used (P <0.05). RESULTS: The densities in the AS and PS ROIs were significantly smaller than the reference bone densities before RME therapy. Both AS and PS ROIs showed significant decreases in density from T0 to T1, significant increases from T1 to T2, and no significant differences from T0 to T2. CONCLUSIONS: The effective opening of the midpalatal suture by RME in prepubertal subjects was associated with a significant decrease in sutural density. The sutural density after 6 months of retention post-RME indicated reorganization of the midpalatal suture, since it showed values similar to the pretreatment ones.

Continuous forces are more effective than intermittent forces in expanding sutures.

SUMMARY: While both intermittent and continuous forces are commonly used to expand sutures, it remains unclear which force is most effective. Using nickel-titanium (NiTi) open coil springs (50 g) and 3 mm long miniscrew implants (MSIs) for skeletal anchorage, intermittent and continuous forces were used to expand the midsagittal sutures in 18 New Zealand white juvenile male rabbits, 11 weeks of age, for 29 days. In the intermittent group, expansion forces of 50 g were delivered for 5 days (on) and paused for 1 day (off); the on/off cycles were repeated five times. Expansion forces of 50 g were delivered for 29 consecutive days in the continuous group. Longitudinal biometric and histomorphometric analyses were performed to evaluate sutural separation and bone formation using implanted tantalum bone markers and fluorescent bone labelling, respectively. Multilevel modelling procedures were undertaken to compare the groups and time intervals. Continuous forces produced significantly greater overall sutural separation (1.3 mm) than intermittent forces (0.8 mm). Although they were delivered over a period of time 86 per cent as long, intermittent forces produced only 61 per cent of the sutural separation of continuous forces. Between days 7 and 17, continuous forces resulted in significantly greater mineral apposition and bone formation rates than intermittent forces. Intermittent forces produced approximately 59 per cent as much mineral apposition and 61 per cent as much bone formation as continuous forces. Due to greater sutural separation and bone formation, continuous forces provide a more effective approach for separating sutures than intermittent forces.

Maxillary expansion in customized finite element method models.

INTRODUCTION: The aims of this study were to develop a method for constructing a 3-dimensional finite-element model (FEM) of the maxilla and to evaluate the effects of transverse expansion on the status of various midpalatal sutures. METHODS: A 3-dimensional FEM of the craniofacial complex was developed by using computed-tomography images and Bionix modeling software (version 3.0, CANTIBio, Suwon, Korea). To evaluate the differences between transverse expansion forces in the solid model (maxilla without a midpalatal suture), the fused model (maxilla with suture elements), and the patent model (maxilla without suture elements), transverse expansion forces of 100 g were applied bilaterally to the maxillary first premolars and the first molars. RESULTS: The fused model expressed a stress pattern similar to that of the solid model, except for the decreased first principal stress concentration in the incisive foramen area. The patent model, however, had a unique stress pattern, with the stress translated superiorly to the nasal area. The anterior nasal spine and the central incisors moved downward and backward in both solid and fused models but moved primarily downward with a slight backward movement of the anterior nasal spine in the patent model. CONCLUSIONS: Clinical observations of maxillary expansion can be explained by different suture statuses. This efficient and customized FEM model can be used to predict craniofacial responses to biomechanics in patients.

Maxillary protraction with and without maxillary expansion: a finite element analysis of sutural stresses.

INTRODUCTION: In this finite element study, we compared the stress patterns along the various craniofacial sutures with maxillary protraction with and without expansion. METHODS: Two 3-dimensional analytic models were developed, 1 simulating maxillary protraction and the other simulating maxillary protraction with expansion. The model consisted of 108799 10 node solid 92 elements (tetrahedron), 193633 nodes, and 580899 degrees of freedom. RESULTS: The overall stresses after maxillary protraction with maxillary expansion were significantly higher than with a facemask alone. The magnitude of stress on the craniofacial sutures with maxillary protraction alone was in the range of a few millinewtons per square millimeter, whereas, with maxillary protraction with maxillary expansion, the stresses ranged from a few newtons per square millimeter to a few hundred newtons per square millimeter. The pattern of stress distribution also differed with the 2 treatment modalities as did the sutures experiencing maximum and minimum stresses. CONCLUSIONS: The osteogenic potential of such low stresses after maxillary protraction can be questioned. High stresses generated in various craniofacial sutures after maxillary protraction with expansion are responsible for disrupting the circummaxillary sutural system and presumably facilitating the orthopedic effect of the facemask.

Sutural strain in orthopedic headgear therapy: a finite element analysis.

INTRODUCTION: The goal of this study was to analyze the strains induced in the sutures of the midface and the cranial base by headgear therapy involving orthopedic forces. Does the mechanical signal induced in the sutures sufficiently account for a growth-influencing effect? METHODS: A finite element model of the viscerocranium and the neurocranium was used. It consisted of 53,555 tetrahedral elements and 97,550 nodes. The strain induced in the sutures of the cranial base and the midface when applying orthopedic headgear forces of 5 and 10 N was computed and recorded with an interactive measurement tool. RESULTS: The magnitude and the distribution of the measured strains depended on the level and the direction of the acting force. Overall, the strain values measured at the sutures of the midface and the cranial base were moderate. The measured peak values at a load of 5 N per side were usually just below 20 microstrain irrespective of the force direction. A characteristic distribution of strain values appeared on the anatomical structures of the midface and the cranial base for each vector direction. The measurements based on the finite element method provided a good overview of the approximate magnitudes of sutural strains with orthopedic headgear therapy. The signal arriving in the sutures is apparently well below threshold, since the maximum measured strains in most sutures were about 100 fold lower than the minimal effective strain. A skeletal effect of the orthopedic headgear due to a mechanical effect on sutural growth cannot be confirmed from these results. CONCLUSIONS: The good clinical efficacy of headgear therapy with orthopedic forces is apparently based mainly on dentoalveolar effects, whereas the skeletal effect due to inhibition of sutural growth is somewhat questionable.

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.

Analysis of sutural strain in maxillary protraction therapy.

OBJECTIVE: The goal of the study was to examine the strain in the sutures of the midface and the cranial base with maxillary protraction therapy and to clarify whether such stretching suggests a skeletal effect of the apparatus employed for that purpose. MATERIALS AND METHODS: Using a finite elements model, a maxillary protraction therapy was simulated with various force levels and vectors, and the strains appearing at the sutures (in microstrain) were measured at the midface and the cranial base. The simulation model we employed consisted of 53,555 individual elements; the simulated forces were 2 x 3 N and 2 x 5 N, while the vectors of the applied forces were in the anterior and anterior caudal direction. RESULTS: The maximum measured strains were on average below 10 microstrain, while higher values were measured only at the nasal bone and at the cranial base at the oval and spinous foramina with anterior directed force vectors (26.4 microstrain). With an anterior-caudal force vector, the measured values were usually lower. DISCUSSION: The measured strains were on average about hundredfold lower than the Frost thresholds (2000 microstrain). It does not seem probable that the strains occurring upon maxillary protraction therapy suffice to stimulate any additional bone growth. CONCLUSION: The good clinical efficacy of maxillary protraction therapy is apparently based, for the most part, on dental effects, while its skeletal effects still remain doubtful.

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.

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.

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.

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.