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Effects of the LactoSorb bioabsorbable plates on the craniofacial development of rabbits: direct morphometric analysis using linear measurements.

The use of plates for the treatment of fractures can affect craniofacial bone development. This study investigated the effect of bioabsorbable plates and titanium microscrews on the growth of the craniofacial skeleton of rabbits (Oryctolagus cuniculus), in the neonatal period. A LactoSorb plate and PROMM titanium microscrews were positioned across the coronal suture in animals in the study group. In the control group, only PROMM titanium microscrews were attached to the cranium. Anteroposterior linear measurements were obtained using 3 different gauging devices: digital precision caliper, EKG caliper and nylon string. Frontal-nasal (FN) distances were statistically different between the left and right side when the digital caliper (P<or=0.01), EKG caliper (P<or=0.01) and nylon string (P<or=0.05) were used. Mean right-side FN distances in the control and study groups were significantly different (P<or=0.05) when measured with the EKG caliper. Normal neonatal craniofacial growth of rabbits was affected by the use of bioabsorbable plates in this study. Further studies should be conducted to investigate whether these plates affect growth in human beings.

Absorbable Implants↗

Craniofacial development of the rat with respect to vestibular orientation.

The vestibular orientation was applied in the present work. Its purpose was to contribute to the knowledge of the craniofacial development of the growing rat. Sagittal cuts were made in 91 crania from Wistar rats (44 males and 47 females) at 8, 15, 30 and 60 days of age. The x and y coordinates of the sagittal points were determined. The sagittal intersection of the vestibular plane was employed as the abscissa and its perpendicular at the mid point of the external semicircular canal (mesovestibion) as the ordinate. Cranial diagrams were constructed in which the length of the sagittal projection of each bone and its angulation with respect to the abscissa were measured. It was confirmed a progressive evolution towards orthocrania due to the bone rotation complexes, which characterized three cranial regions: the anterior region (frontal-ethmiodal-facial complex) with trigonometric rotation; the mid region (parietal-sphenoidal complex) remained stable, and the posterior region (interparietal-occipital complex) with clockwise rotation. Each complex had its own pattern of rotation. The causal factors reside in the differential increment between the functional components: (a) neurocranium-splanchnocranium, (b) neurocranium-cervical column, (c) dorsal neurocranium-basilar neurocranium and (d) dorsal splanchnocranium-basilar splanchnocranium. Its etiology obeys to the functional requirements induced by the adaptation of the modern rodents.

Animals↗

Effect of in utero exposure to anticonvulsants on craniofacial development and growth.

It has been widely reported that some children exposed to anticonvulsants in utero have a characteristic pattern of craniofacial anomalies including a broad, low nasal bridge with a short upturned nose, wide mouth, low set ears, epicanthal folds, and ocular hypertelorism, while others show no evidence of craniofacial abnormalities. The purpose of this paper is to define the craniofacial features in nine exposed children using anthropometric measurements and frontal and lateral cephalometric radiographs. These children were identified at birth as part of a prospective study of infants exposed to anticonvulsants at the Boston Hospital for Women (now part of the Brigham and Women's Hospital). At birth, none of these infants had any major malformations; at 4 to 10 years of age, none demonstrated any growth deficiency or mental deficiency, and all external craniofacial measurements were within the normal range. However, cephalometric analyses demonstrated a pattern of reduced bony interorbital distance, maxillary size, mandibular length, cranial base and skull size, and a reduction in nose dimensions when compared to data of normal populations. This study demonstrates the inadequacy of external measurements in determining the details of underlying craniofacial architecture. The data also suggest that a subtle craniofacial change occurs in exposed children which is characterized by a decrease in bony interorbital distance and the size of the cranial base and maxilla with concomitant decreases in nose and mandibular dimensions.

Abnormalities, Drug-Induced↗

Cell dissociation experiments reveal that positional information operates in the chicken frontonasal mass.

In this study we examined the role of cell-cell affinity in patterning the avian frontonasal mass-the facial prominence that forms the prenasal cartilage and premaxillary bone. Reconstituted cell pellets derived from undifferentiated, frontonasal mass mesenchyme were recombined with facial epithelium and grafted to host embryos to continue development. We determined that the cells reestablished a recognizable frontonasal mass pattern and were able to induce egg teeth in overlying ectoderm. Further analysis revealed there were region-specific differences in the cartilage patterns such that central recombinations were more likely to form a straight cartilage rod, whereas lateral mesenchyme pellets were more likely to form complex, branched cartilage patterns. The basis for the pattern differences was that central mesenchyme cells showed preferential clustering in the cartilage condensations in the center of the graft, whereas lateral cells were spread throughout as determined by dye labeling and quail chicken chimeras. The disruption of cell contacts temporarily delayed onset of gene expression but by 48 h both Msx2 and Dlx5 were expressed. Msx2, in particular, had very clear edges to the expression domains and often the pattern of expression correlated with type of cartilage morphology. Together, these data suggest that an important patterning mechanism in the face is the ability of mesenchymal cells to sort out according to position and that Msx2 may help repress chondrogenic potential in the lateral frontonasal mass.

Animals↗

Roentgen stereometry with the aid of metallic implants in hemifacial microsomia.

Displacement of the mandible and the maxilla with growth in relationship to the frontal bone was recorded in eleven children with hemifacial microsomia, aged 3 to 14 years at the initial examination. The goals were to assess the efficiency of the method for accurate recording of articular growth and to obtain information on facial development in each of these children. Correction of the skeletal asymmetry was not attempted during observation periods of from 707 to 1,484 days. In continued observations three of the children were treated with functional appliances. Roentgen stereometry with the aid of metallic implants proved to be an efficient method for highly accurate recordings of articular facial growth in relationship to the frontal bone. Displacement of the jaws was asymmetrical in all of the examined children as determined in the frontal and transverse planes of the head. In about 50 percent of the children the degree of asymmetry increased in one plane while it decreased in the other plane. No correlation was found between the extent of the mandibular deformity, as seen on orthopantomograms, and the displacements of the mandible. Generally, the displacement of the maxillary bones corresponded with the displacement of the mandible. Articular growth of the jaws was redirected toward a more favorable pattern in two of the children during the time they used a functional appliance. In the third child the use of a functional appliance had no such effect.

Activator Appliances↗

Experimental effects of bone plating in infancy on craniomaxillofacial skeletal growth.

The potential effects of mini- and microfixation on craniofacial development was investigated in an animal model. Twenty-four rabbits had amalgam markers placed bilaterally at the lambdoid, coronal, and frontonasal sutures at 28 days of age. In group 1, plating was not done and served as controls. In groups 2 to 4, single 2- and 4-hole microplates and 4-hole miniplates were fixed across the left coronal suture. The right suture was not plated. After 6 months, intermarker distances and craniofacial angles were measured radiographically. Coronal sutures underneath the plates were also histologically evaluated. Plating across the coronal suture resulted in local anteroposterior constriction of marker distances that did not differ with the type of fixation used. More distant markers, however, were increased in all specimens as a compensation and, as a result, the cranionasal length of all groups were similar. No change in craniofacial angles was observed from that of the controls. Sutural morphology on the side of fixation was altered with decreased widths, cellular numbers, and bone deposition. These experimental results demonstrate that early plate application in a normal calvarium results in local growth restriction that can be overcome by regional bone growth compensation.

Analysis of Variance↗

Stability and plasticity of neural crest patterning and branchial arch Hox code after extensive cephalic crest rotation.

The extent to which the spatial organisation of craniofacial development is due to intrinsic properties of the neural crest is at present unclear. There is some experimental evidence supporting the concept of a prepattern established within crest while contiguous with the neural plate. In experiments in which the neural tube and premigratory crest are relocated within the branchial region, crest cells retain patterns of gene expression appropriate for their position of origin after migration into the branchial arches, resulting in skeletal abnormalities. But in apparent conflict with these findings, when crest is rerouted by late deletion of adjacent crest, infilling crest alters its pattern of gene expression to match its new location, and a normal facial skeleton results. In order to reconcile these findings thus identify processes of relevance to the course of normal development, we have performed a series of neural tube and crest rotations producing a more extensive reorganisation of cephalic crest than has been previously described. Lineage analysis using DiI labelling of crest derived from the rotated hindbrain reveals that crest does not migrate into the branchial arch it would have colonised in normal development, rather it simply populates the nearest available branchial arches. We also find that crest adjacent to the grafted region contributes to a greater number of branchial arches than it would in normal development, resulting in branchial arches containing mixed cell populations not occurring in normal development. We find that after exchange of first and third arch crest by rotation of r1-7, crest alters its expression of hoxa-2 and hoxa-3 to match its new location within the embryo resulting in the reestablishment of the normal branchial arch Hox code. A facial skeleton in which all the normal components are present, with some additional ectopic first arch structures, is formed in this situation. In contrast, when second and third arch crest are exchanged by rotation of r3 to 7, ectopic Hox gene expression is stable, resulting in the persistence of an abnormal branchial arch Hox code and extensive defects in the hyoid skeleton. We suggest that the intrinsic properties of crest have an effect on the spatial organisation of structures derived from the branchial arches, but that exposure to increasingly novel environments within the branchial region or "community effects" within mixed populations of cells can result in alterations to crest Hox code and morphogenetic fate. In both classes of operation we find that there is a tight link between the resulting branchial arch Hox code and a particular skeletal morphology.

Animals↗

Effects of resorbable fixation on craniofacial skeletal growth: a pilot experimental study.

The effects of fixation composed of resorbable polymers on craniofacial development was investigated in an animal model. Fourteen rabbits had amalgam markers placed bilaterally at the lambdoid, coronal, and frontonasal sutures at 28 days of age. Seven animals (group I) were not plated and served as controls. The other 7 animals (group II) were fixed across the left coronal suture with a 4-hole, compressive resorbable plate. After 6 months, intermarker distances (growth) were measured radiographically, and the amount of fixation degradation was determined by extracted plate weights. Resorbable plating across the coronal suture resulted in local marker constriction adjacent to fixation. Compensatory lengthening of the distal aspect of the frontal bone occurred, however resulting in unaltered total cranionasal lengths compared with that of control animals. Plate degradation occurred with a mean decrease of 7% from their original weights. Molecular weight analysis of the plate differences, however, was not done. This initial study indicates that a large plate size and slow resorption properties of polymer fixation can have a similar restrictive effect on bone growth as that of metal fixation. Whether thinner plates or more rapidly resorbing polymers will permit normal growth in this animal model awaits further testing.

Animals↗

Taking stock: passing the torch, who has the light? Reflections about teaching orthodontics at the occasion of the retirement of Prof. Lysle E. Johnston, Jr PhD.

In the Marburg (Germany) 5-year dental curriculum, students enter the orthodontic department in the middle of their third year. Our teaching is student-centered and problem-solving oriented. From day 1 our students are trained to diagnose in three separate levels of development i.e. (i) craniofacial growth, (ii) development of the dentition and (iii) maturation of function. These three levels are kept separate throughout patient examination and up to the strategic treatment planning phase. The examination is performed with the help of three checklists, one for the facial morphology, one for the dentition and one for function. The three resulting problem lists then undergo reduction by selecting one 'key problem' for each level. Next, for every key problem three 'standard solutions' are offered, not in the form of appliances but as vectors that can modify growth. Finally, in a strategic planning phase, one treatment option from each of the three levels is selected and combined in a single, be it hypothetical, treatment plan. Parallel to these, students are exposed to treatment mechanics through the presentation of selected orthodontically treated patients. In our experience the advantage of this diagnostic procedure lies in the structured organization that serves as a GPS system for student and teacher and enables them a clear communication about where they are and what has to be done. By design, treatment options have taken priority over treatment mechanics. We are confident that our students, equipped with real life diagnostic skills, are well prepared for their orthodontic future.

Curriculum↗

Monitoring growth during orthodontic treatment.

The relationship between somatic growth and orthodontic treatment has been limited to the evaluation of body height and skeletal age relative to craniofacial development. The aim of this study was to evaluate the correlation of anthropometric and biochemical measures of general growth with facial and occlusal changes during the early treatment of Class II Division 1 malocclusion. Findings are reported from 46 children, ages 7.20 to 12.85 years (skeletal ages, 5.75 to 12.75 years), who are enrolled in a prospective clinical trial. Body and knee heights were measured monthly, with a Holtain stadiometer and a Knee Height Measuring Device, respectively. Every three months, serum levels were measured of the hormone dehydroepiandrosterone sulfate (DHEAS), an androgen associated with growth in midchildhood, and osteocalcin, an indicator of bone turnover. Significant correlations existed between knee height and various occlusal measurements, but mandibular length was not significantly correlated with knee height and DHEAS levels. Knee height correlated significantly (P < .05) with DHEAS and osteocalcin only in 46% and 37% of the children, respectively. The results indicate that the evaluated biochemical measures, at the time intervals considered, may not increase the accuracy of growth depiction by physical measures alone (height and skeletal maturation).

Anthropometry↗

[Frequency analysis of the EMG power spectrum of the anterior temporal and masseter muscles in children and adults].

For the investigation of the functional change of the masticatory muscles along with growth and development, the frequency analysis of the EMG power spectrum was carried out. The subjects were 6 children (5 males and 1 female) with full deciduous dentition (Hellman's dental age IIA) aged 4.5 +/- 0.2 years and 6 adults (4 males and 2 females) with full permanent dentition aged 27.7 +/- 3.8 years. EMG signals were recorded bilaterally by means of bipolar silver surface electrodes from the anterior temporal and masseter muscles when the subjects were chewing chewing gum or performing maximum clenches in the intercuspal position. A fast Fourier transform (FFT) algorithm was used to obtain the power spectrum of the EMG signal. As the total power value from 62.5 to 1000 Hz was 100 per cent, the mean frequencies at 25, 50, 75 and 90 per cent of the cumulative power were calculated. The results were as follows: 1. The mean frequencies at each ratio of the cumulative power were age-dependent and EMG power spectrum patterns significantly shifted to lower frequencies in the muscles of the adults. 2. No statistically significant differences between the chewing and clenching, the anterior temporal and masseter muscle and the left and right side were observed in each group.

Adult↗

An autosomal dominant mutation of facial development in a transgenic mouse.

We have created a transgenic mouse which showed an autosomal dominant mutation of facial development. This facial malformation was characterized by a short snout and a twisted upper jaw. All offspring showing the dysmorphic phenotype carried the injected gene. In order to analyze the primary cause of this mutation, newborn mice and embryos were examined. The outcome was that the malformation of nasal and premaxillary bone was not the primary defect but was a secondary event. The primary cause of this dysmorphism was a developmental defect in the first branchial arch. Genomic DNA fragments flanking the insertion site of this mutant mouse were cloned. Using these fragments, we have assigned the integration site to chromosome 13. The gene responsible for a previously reported mutant mouse, one which also has a short snout, is also reported to be on chromosome 13. In the fragments flanking the insertion site of the transgenic mouse, at least one fragment was highly conserved in mammals. These results indicate that this malformation is due to the insertional disruption of a host gene. However, the possibility that this mutation is caused by an inappropriate expression of the injected gene still remains to be investigated.

Animals↗

Development of the squamosomandibular articulation in the Mongolian gerbil (Meriones unguiculatus).

The early development of the squamosomandibular articulation in the Mongolian gerbil was investigated from its inception through the 8th postnatal day. Pregnant gerbils were sacrified beginning on day 18 through day 23 of gestation by chlorofrom inhalation and the fetuses were extirpated and decapitated. Neonatal gerbils, 1-8 days of age, were also sacrificed. The severed heads were frozen in a cryostat and sectioned at 14mum in frontal and transverse planes and stained in 1% aqueous Safranin 0. The anlage of the mandibular joint along with membranous bony deposits lateral to Meckel's cartilage in the vicinity of the presumptive body and ramus first appeared on the 18th gestational day. Condylar chondrogenesis occurred on the 20th prenatal day, and by day 22 of gestation chondrocytic hypertrophy was noted preparatory to osteogenesis. The presumptive articular disc was observed on the 21st gestational day while an upper and lower synovial cavity was discernible on the 22nd prenatal day. The squamosa and zygoma were first noted on the 20th postcoital day. There appeared to be a developmental lag from onset through completion of the gerbil squamosomandibular joint formation in comparison with that reported for the mouse and rat.

Age Factors↗

Growth of the vomero-premaxillary suture in children with bilateral cleft lip and palate. A histological and roentgencephalometric study.

The significance of the vomero-premaxillary suture (VPS) in mid-facial development in patients with complete bilateral cleft lip and palate (C-BCLP) was evaluated. Histological analysis of the VPS in eight specimens, ranging in age from full term to 22 months, revealed evidence of growth at both sutural borders. Various theories to explain the consistent presence of secondary cartilage, localized mainly to the posterior end of the suture, were assessed. It was considered most likely that the formation of cartilage was promoted by mechanical stresses, set up during a period of rapid growth. Roentgencephalometric data from seven C-BCLP patients (age range: 2-7 months) demonstrated the existence of a true, rather than a relative, premaxillary protrusion. Five patients had metallic implants inserted on either side of the VPS at the time of initial surgery and were followed up roentgencephalometrically to ages ranging from 5 to 36 months. Although continuous growth was recorded in the VPS, there was a post-surgical decrease in the premaxillary protrusion. On the basis of both the histology and roentgencephalometry it was concluded that traumatic surgery involving the VPS would be likely to contribute to the impaired mid-facial growth sometimes seen in operated C-BCLP patients.

Cephalometry↗

Growth changes in head posture related to craniofacial development.

Cross-sectional studies have demonstrated an association between craniocervical angulation and craniofacial morphology. It was the aim of the present study to determine if the growth coordination suggested by this association could be detected in a longitudinal analysis of growth changes in posture and craniofacial morphology. The sample comprised 43 children, 20 girls and 23 boys. Cephalometric radiographs obtained in the natural head position (mirror position) were taken on two occasions. Mean age at the first observation was 9.5 years; mean period of observation was 2.7 years with a range from 1 to 4 years. Forty-one reference points and four fiducial points were digitized on each film. Individual growth changes were determined by computerized structural superimposition of the digitized sets of points. Correlation coefficients were calculated between growth changes in 11 postural and 35 morphologic variables. Correlations of r = 0.41-0.55 (P less than 0.01) were found between the change in craniocervical angulation and the true growth rotation of the mandible as assessed by the method of structural superimposition. On the average, a reduction of the craniocervical angle was seen in connection with increased forward rotation of the mandible and an increased craniocervical angle was found in conjunction with a less-than-average forward rotation of the mandible. The true mandibular rotation was masked by remodeling of the lower mandibular border. The changes in the conventional measures of head posture--the craniovertical angles--during the observation period showed no associations with the growth changes in craniofacial morphology.

Cephalometry↗

Myofibroblasts in palatal wound healing: prospects for the reduction of wound contraction after cleft palate repair.

The surgical closure of orofacial clefts is considered to impair maxillary growth and dento-alveolar development. Wound contraction and subsequent scar tissue formation, during healing of these surgical wounds, contribute largely to these growth disturbances. The potential to minimize wound contraction and subsequent scarring by clinical interventions depends on the surgeon's knowledge of the events responsible for these phenomena. Fibroblasts initiate wound contraction, but proto-myofibroblasts and mature myofibroblasts are by far the most important cells in this process. Myofibroblasts are characterized by their cytoskeleton, which contains alpha-smooth-muscle actin. Additionally, their contractile apparatus contains bundles of actin microfilaments and associated contractile proteins, such as non-muscle myosin. This contractile apparatus is thought to be the major force-generating element involved in wound contraction. After closure of the wound, the myofibroblasts disappear by apoptosis, and a less cellular scar is formed. A reduction of contraction and scarring might be obtained by inhibition of myofibroblast differentiation, stimulation of their de-differentiation, stimulation of myofibroblast apoptosis, or impairment of myofibroblast function. In this review, we will discuss all of these possibilities, which ultimately may lead to a better outcome of cleft palate surgery.

Animals↗

Frequency analyses of EMG power spectra of anterior temporal and masseter muscles in children and adults.

To study the functional change of masticatory muscles during growth and development, frequency analyses of surface electromyogram (EMG) power spectra were carried out. The subjects were six children (five males and one female), aged 4.5 +/- 0.2 years, having full deciduous dentition (Hellman's dental age IIA) and six adults (four males and two females), aged 27.7 +/- 3.8 years, having full permanent dentition. EMG signals were recorded bilaterally by using bipolar silver-surface electrodes from the anterior temporal and masseter muscles while the subjects were chewing gum and while performing maximum clenching in the intercuspal position. A fast Fourier transform algorithm was used to obtain the power-spectral density function and the power spectra of the EMG signals. Since the total power value from 62.5 to 1000 Hz was 100 percent, the frequencies at 25, 50, 75, and 90 percent of the cumulative power were calculated. The results showed that the frequencies at every percent of the cumulative power were age-dependent and that the EMG power spectra patterns in adult muscles were shifted to significantly lower frequencies than those in child muscles. The shift was probably caused by differences in the proportion of fiber type and fiber size between muscles of children and adults.

Adult↗

Retinoic acid exposure of the mouse on embryonic day 9 selectively spares derivatives of the frontonasal neural crest.

Retinoic acid is known to perturb craniofacial development and can be used to understand processes controlling early embryonic development of the face. The effects of retinoic acid on mouse craniofacial development were studied by administration of a single dose (25-200 mg/ kg) of all-trans retinoic acid (RA) to timed pregnant C57BL6/J mice at gestational days (gd) 8.25, 9, or 10. RA exposure on gd 8.25 or gd 10 resulted in craniofacial defects in fetuses but gd 9 exposure revealed a differential effect of RA depending upon whether tissues were derived from branchial arch or frontonasal neural crest. Embryos exposed to RA at gd 9 showed a dose-dependent effect of RA on branchial arch derived tissues; first arch derivatives were most severely affected with the mandible and zygoma becoming severely dysplastic at the highest dose of RA (200 mg/kg). However, RA exposure on gd 9 completely spared frontonasal neural crest-derived tissues. Paired premaxillae nasal and frontal bones as well as the cartilaginous nasoethmoid region and nasal capsule containing the osseous vomer showed no statistical difference from those of control animals. These studies showed a temporal and differential sensitivity to RA and may suggest a developmental heterogeneity of the cephalic neural crest cells destined to participate in formation of craniofacial structures.

Animals↗