Anatomic basis for vascularized outer-table calvarial bone flaps

The vascularization of the scalp and calvarium was studied in cadavers to better define the design of vascularized split- or full-thickness calvarial bone flaps. Selective dye injections of the superficial temporal and internal maxillary arteries established a horizontal and vertical network of vessels within and between each layer of the scalp. The periosteum of the frontoparietal region continues over the temporal aponeurosis as a separate, distinct layer, the innominate fascia, which is irrigated by numerous proximal branches of the superficial and deep temporal arteries. The periosteum can sustain the outer table of the calvarium by means of multiple small, vertical perforators. Between the periosteum and the outer table is a thin areolar layer of subperiosteum which continues beneath the temporal muscle. We feel that vascularized outer-table calvarial flaps can safely be pedicled using only the temporal aponeurosis, innominate fascia, and periosteum without including the galea or temporal muscle.     

Volume maintenance of inlay bone grafts in the craniofacial skeleton

Although the clinical use of inlay bone grafts is widespread in craniofacial surgery, the dynamics of inlay bone grafting to the craniofacial skeleton have never been well characterized. Previous work demonstrated that volume maintenance of bone grafts in the onlay position is a consequence of their microarchitectural features, rather than their embryological origins. The purpose of this study was to investigate whether the properties determining the volume maintenance of bone grafts in the onlay position in the craniofacial skeleton could be extended to bone grafts in the inlay position. It was hypothesized that volume maintenance of an inlay bone graft could be better explained on the basis of the microarchitectural features of the graft (cortical versus cancellous composition), rather than its embryological origin (membranous versus endochondral), and that the primary determinant of bone graft behavior is the interaction between the microarchitectural features of the bone graft and the local mechanical environment in which the bone graft is placed. Cortical and cancellous bone grafts were harvested from the iliac crest (endochondral origin) of 25 New Zealand white rabbits, and cortical bone was harvested from the mandible (membranous origin) of each rabbit. Four 7-mm trephine holes were made in the cranium of each rabbit, posterior to the coronal suture. Each defect was filled with endochondral cortical bone, endochondral cancellous bone, or membranous cortical bone or was left as an ungrafted control specimen. Animals were killed at 3, 8, or 16 weeks. Crania were subjected to micro-computed tomographic and histological assessments. Micro-computed tomographic analysis demonstrated significant increases in actual bone volume from time 0 to the time of death for all types of grafts. Cortical bone demonstrated significant increases in space-occupying volume at all time points. By 16 weeks, no statistically significant difference in either the actual bone volume or the space-occupying volume according to graft type could be detected. There was no resorption of the inlay bone grafts; in fact, all bone types exhibited increased volume. Cancellous bone demonstrated the greatest capacity to increase actual bone volume. All bone graft types seemed to reach a steady-state bone volume, as if controlled by a local regulator. The regulator is likely the local mechanical environment in which the grafts were placed, as corroborated by the findings that the bone grafts seemed to recapitulate the characteristics of the bone in which they were placed, rather than maintaining their native characteristics.     

Distraction osteogenesis of the craniofacial skeleton

In summary, distraction osteogenesis is a safe and effective means of achieving bone lengthening. These techniques were originally applied to the long bones of the extremities; over the past 10 years they have been effectively applied to the bones of the craniofacial skeleton. The new bone regenerate that is observed after distraction osteogenesis is stable, and relapse rates after skeletal advancement are believed to be lower than with conventional osteotomy and bone graft techniques. There is considerable variability in distraction protocols employed in clinical practice, including differences in the types of devices used and in the rate, rhythm, latency, and period of consolidation for distraction osteogenesis. The greatest application for distraction osteogenesis in the craniofacial skeleton has been with mandible lengthening, for which there is presently a 10-year clinical experience. Midfacial advancement is a newer application of distraction osteogenesis, for which clinical experience has been accrued over the past 5 years. This latter experience indicates that distraction osteogenesis is a viable treatment option for lengthening of the hypoplastic mandible and midface. These techniques have advantages over conventional means of bone graft and rigid fixation because of the quality of the bone regenerate, the decrease in the long-term relapse rate of the advanced bone segments in both the mandible and the midface, and the simultaneous soft-tissue elongation that accompanies the distraction process. Distraction osteogenesis is particularly applicable to the correction of severe deformities of the mandible and midface in children with developmental hypoplasia and syndromic craniosynostosis. However, growth is an added variable in this patient population. The amount of overcorrection in lengthening of the hypoplastic bone required to compensate for continued growth discrepancy of the adjacent facial bones is difficult to predict. Therefore, the families of these patients should be informed that many children will require repeated operations at a later age as they reach skeletal maturity.     

Distraction osteogenesis of the craniofacial skeleton

Distraction osteogenesis is becoming the treatment of choice for the surgical correction of hypoplasias of the craniofacial skeleton. Its principle is based on the studies of Ilizarov, who showed that osteogenesis can be induced if bone is expanded (distracted) along its long axis at the rate of 1 mm per day. This process induces new bone formation along the vector of pull without requiring the use of a bone graft. The technique also provides the added benefit of expanding the overlying soft tissues, which are frequently deficient in these patients. This article reviews the authors' 11-year clinical and research experience with mandibular distraction osteogenesis. It highlights the indications and contraindications of the technique and emphasizes the critical role that basic science research has played in its evolution.     

Elastic properties of external cortical bone in the craniofacial skeleton of the rhesus monkey

Knowledge of elastic properties and of their variation in the cortical bone of the craniofacial skeleton is indispensable for creating accurate finite-element models to explore the biomechanics and adaptation of the skull in primates. In this study, we measured elastic properties of the external cortex of the rhesus monkey craniofacial skeleton, using an ultrasonic technique. Twenty-eight cylindrical cortical specimens were removed from each of six craniofacial skeletons of adult Macaca mulatta. Thickness, density, and a set of longitudinal and transverse ultrasonic velocities were measured on each specimen to allow calculation of the elastic properties in three dimensions, according to equations derived from Newton's second law and Hooke's law. The axes of maximum stiffness were determined by fitting longitudinal velocities measured along the perimeter of each cortical specimen to a sinusoidal function. Results showed significant differences in elastic properties between different functional areas of the rhesus cranium, and that many sites have a consistent orientation of maximum stiffness among specimens. Overall, the cortical bones of the rhesus monkey skull can be modeled as orthotropic in many regions, and as transversely isotropic in some regions, e.g., the supraorbital region. There are differences from human crania, suggesting that structural differences in skeletal form relate to differences in cortical material properties across species. These differences also suggest that we require more comparative data on elastic properties in primate craniofacial skeletons to explore effectively the functional significance of these differences, especially when these differences are elucidated through modeling approaches, such as finite-element modeling.     

Patterns of covariation in the hominoid craniofacial skeleton: implications for paleoanthropological models

Living species are often used as analogues for fossil ones. When this is done, the implicit assumption is made that hominids and living hominoids vary in the same way. This paper addresses the validity of this assumption by comparing patterns of facial variation among humans and African apes. In particular, it addresses three major questions that underlie approaches to reconstructing hominid relationships. First, is phenotypic variation similar between closely related species? Second, if it is dissimilar, why? Third, is it feasible to use analogue species for modeling purposes? Measurements are obtained from 542 crania of adult apes and humans. Care is taken to choose homologous data, and account for differences in population size and structure. Variance/covariance and correlation matrices among the species are compared using common principal component (CPC) analysis, random skewers methods and matrix correlations. Morphological distances (D(2)) are calculated between population means, and between randomized pairs of individuals within each population, to evaluate intraspecific variation. Morphological distances are also calculated between randomized pairs of individuals using the variation patterns of analogue populations, in order to evaluate the efficacy of such substitutions. Results show that while the hominoids share a similar pattern of facial variation overall, the patterns do diverge. This difference generally corresponds to the phylogenetic relationships among these species, suggesting that patterns of variation may have diverged through time in the large bodied hominoids. Because interpretation of relationships in the fossil record is confounded by a lack of understanding of how variation changes through time, exploration of such patterns of divergence can provide important clues to understanding human evolution. Additionally, neglecting to account for this divergence when using living analogues as variation "yardsticks" can give rise to interpretations of the fossil record that are more speciose than is warranted.     

Blood coagulation and bone metabolism: some characteristics of the bone resorptive effect of thrombin in mouse calvarial bones in vitro

Chronic inflammatory processes are often associated with bone resorption. Stimulated by the current great interest in the role of coagulation factors in inflammation and immune injury, we have studied the effect of thrombin on mouse calvarial bones in vitro. Thrombin caused a dose-dependent (0.1-7 U/ml) stimulation of 45Ca release from neonatal mouse calvarial bones. Thrombin also stimulated the mobilization of stable calcium and inorganic phosphate, the release of 3H from [3H]proline-labelled calvaria, the production of lactate and the release of the lysosomal enzymes, beta-glucuronidase and beta-N-acetylglucosaminidase. Thrombin also enhanced 45Ca release from fetal rat long bones, although this bone resorption assay was less sensitive to thrombin than the mouse calvarial system. The bone resorption stimulatory activity of thrombin in mouse calvaria could be inhibited by calcitonin and an increased concentration of phosphate in the culture medium. Thrombin-induced 45Ca release in mouse calvaria was sensitive to inhibition by hydrocortisone and dexamethasone. By contrast, 45Ca release response to parathyroid hormone was insensitive to corticosteroids. The prostaglandin synthetase inhibitors indomethacin, meclofenamic acid and naproxen and 5,8,11,14-eicosatetraynoic acid reduced 45Ca release from thrombin-stimulated calvaria. However, significant stimulation by thrombin could be achieved also in bones treated with inhibitors of arachidonate metabolism. The results obtained suggest that thrombin can stimulate cell-mediated bone resorption by an osteoclast-dependent mechanism. The mechanism of action may involve both prostaglandin-dependent and prostaglandin-independent pathways. Our findings indicate that thrombin may contribute to the bone resorptive processes seen in periodontal disease and rheumatoid arthritis.     

A comparative analysis of the microarchitecture of cortical membranous and cortical endochondral onlay bone grafts in the craniofacial skeleton

Previous work in this laboratory established that an onlay bone graft's survival is determined primarily by its relative cortical and cancellous composition rather than its embryologic origin. A volumetric analysis of external bone graft resorption, however, does not explain the internal microarchitectural changes that may be occurring as these grafts become incorporated. To expand the knowledge of bone graft dynamics beyond volumetric parameters, a better understanding of the internal processes of bone graft remodeling is needed. In this comparative study of cortical onlay bone graft microarchitecture, the authors propose to show that cortical onlay bone grafts undergo measurable internal microarchitectural changes as they become incorporated into the surrounding craniofacial skeleton. In addition, the authors propose to further demonstrate similarities between the internal microarchitecture of cortical onlay bone grafts of different embryologic origin over time. Twenty-five adult New Zealand White rabbits were used for this study. They were divided into two groups of eight animals and one group of nine. The groups were killed at 3, 8, and 16 weeks. Cortical membranous and endochondral bone grafts were placed subperiosteally onto each rabbit's cranium. In addition, five ungrafted cortical endochondral and membranous bone specimens were used as controls. Microcomputed tomography (MCT) scanning and histomorphometric analysis were performed on all of the specimens to obtain detailed information regarding the microarchitecture of the cortical bone grafts. The parameters of bone volume fraction, bone surface area to volume, mean trabecular number, and anisotropy were used to give quantitative information about a bone's micro-organization. The results showed that there is no statistically significant difference between the cortical endochondral and the cortical membranous bone grafts for bone volume fraction, bone surface to volume, mean trabecular number, and anisotropy measurements for all time points. There were, however, statistically significant differences when comparing the control and 3-week groups to the 16-week group for all parameters. The advanced MCT technology and histomorphometric techniques proved to be effective in providing a qualitative and quantitative ultrastructural comparison of cortical endochondral and membranous onlay bone grafts over time. In this study, a statistically significant change in the internal microarchitecture of cortical onlay bone grafts of different embryologic origins was seen as they were remodeled and resorbed at all time points. Specifically, the onlay cortical bone grafts developed a less dense, more trabecular, and less organized internal ultrastructure. In addition, no difference in the three-dimensional ultrastructure of cortical endochondral and membranous bone was found. These results challenge some of the currently accepted theories of bone-graft dynamics and may eventually lead to a change in the way clinicians approach bone-graft selection for craniofacial surgery.     

Age-related changes of the craniofacial skeleton: an anthropometric and histologic analysis.

With the development of increasingly sophisticated methods for the alteration of bony facial form consequent to age, it is imperative that the surgeon have a fundamental knowledge of the age-related changes the skeleton may undergo. To understand these changes better, a detailed anthropometric and histomorphic analysis of the craniofacial skeleton as a function of age was undertaken. The study consisted of a detailed craniometric analysis of 160 skulls selected randomly from a Caucasian population of skeletal remains totaling 1500 specimens. Additionally, a histologic analysis of the supraorbital ridge in a separate preserved cadaver population was performed. Although the results showed individual variation as expected, definite changes in craniofacial morphology were observed. These included (1) appreciable reduction of facial height, most marked in the maxilla and mandible, and strongly correlated with loss of teeth, (2) modest increase in facial width, (3) modest increase in facial depth, except in those regions associated with tooth loss, and (4) general coarsening of bony prominences. Histomorphic analysis demonstrated increasing porosity with age, more marked in the female population. Although these changes represent population trends, in any given patient, any or all of them may be present to varying degrees. Surgeons should be aware of these possibilities and consider selective alterations of the skeletal foundation, either separately or in concert with the overlying soft-tissue envelope, in order to optimize the results of surgery for the aging face.     

Reconstruction of the maxilla with a double musculoperiosteal flap in connection with a composite calvarial bone graft

A new technique is shown for a one-stage reconstruction of the mucosa of the floors of the nose and maxillary sinus, the bone structures of the maxilla and the hard palate, as well as the mucosal layers of the hard and soft palates and vestibulum. To accomplish this coverage, a vascularized calvarial bone graft with temporal muscle from one side is combined with a vascularized temporal muscle flap from the other side to achieve a three-layer "sandwich" plasty. The advantage of this procedure is reconstruction of the complete maxillary defect with the possibility of denture rehabilitation and the avoidance of oronasal fenestration. Besides the possible complication of insufficient vascularization of the bone and muscle grafts, the donor defect in the calvarial bone and the missing muscle for mastication are to be considered.     

Roles for fgf8 signaling in left-right patterning of the visceral organs and craniofacial skeleton

Laterality is fundamental to the vertebrate body plan. Here, we investigate the roles of fgf8 signaling in LR patterning of the zebrafish embryo. We find that fgf8 is required for proper asymmetric development of the brain, heart and gut. When fgf8 is absent, nodal signaling is randomized in the lateral plate mesoderm, leading to aberrant LR orientation of the brain and visceral organs. We also show that fgf8 is necessary for proper symmetric development of the pharyngeal skeleton. Attenuated fgf8 signaling results in consistently biased LR asymmetric development of the pharyngeal arches and craniofacial skeleton. Approximately 1/3 of zebrafish ace/fgf8 mutants are missing Kupffer's vesicle (KV), a ciliated structure similar to Hensen's node. We correlate fgf8 deficient laterality defects in the brain and viscera with the absence of KV, supporting a role for KV in proper LR patterning of these structures. Strikingly, we also correlate asymmetric craniofacial development in ace/fgf8 mutants with the presence of KV, suggesting roles for KV in lateralization of the pharyngeal skeleton when fgf8 is absent. These data provide new insights into vertebrate laterality and offer the zebrafish ace/fgf8 mutant as a novel molecular tool to investigate tissue-specific molecular laterality mechanisms.     

Mechanical structure and function of the craniofacial skeleton of the domestic dog.

Masticatory habit is a major factor determining the morphology of the craniofacial skeleton. The craniofacial skeleton essentially comprises a series of bony stress-bearing bridges forming a structural framework. The structural framework of the skull of dog has been described as a rigid trestle-like structure; it can be illustrated by mechanically removing nonresistant areas of bone. It is then found that a framework is produced which is partially rigid (cranium) and partly flexible (rostrum). It is postulated that the flexibility of the rostrum acts to absorb shock and it is suggested that the primate postorbital bar is developed in response to craniofacial morphology which increases compressive bite forces.     

Combinatorial roles for BMPs and Endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton

Bone morphogenetic proteins (BMPs) play crucial roles in craniofacial development but little is known about their interactions with other signals, such as Endothelin 1 (Edn1) and Jagged/Notch, which pattern the dorsal-ventral (DV) axis of the pharyngeal arches. Here, we use transgenic zebrafish to monitor and perturb BMP signaling during arch formation. With a BMP-responsive transgene, Tg(Bre:GFP), we show active BMP signaling in neural crest (NC)-derived skeletal precursors of the ventral arches, and in surrounding epithelia. Loss-of-function studies using a heat shock-inducible, dominant-negative BMP receptor 1a [Tg(hs70I:dnBmpr1a-GFP)] to bypass early roles show that BMP signaling is required for ventral arch development just after NC migration, the same stages at which we detect Tg(Bre:GFP). Inhibition of BMP signaling at these stages reduces expression of the ventral signal Edn1, as well as ventral-specific genes such as hand2 and dlx6a in the arches, and expands expression of the dorsal signal jag1b. This results in a loss or reduction of ventral and intermediate skeletal elements and a mis-shapen dorsal arch skeleton. Conversely, ectopic BMP causes dorsal expansion of ventral-specific gene expression and corresponding reductions/transformations of dorsal cartilages. Soon after NC migration, BMP is required to induce Edn1 and overexpression of either signal partially rescues ventral skeletal defects in embryos deficient for the other. However, once arch primordia are established the effects of BMPs become restricted to more ventral and anterior (palate) domains, which do not depend on Edn1. This suggests that BMPs act upstream and in parallel to Edn1 to promote ventral fates in the arches during early DV patterning, but later acquire distinct roles that further subdivide the identities of NC cells to pattern the craniofacial skeleton.     

The role of rigid skeletal fixation in bone-graft augmentation of the craniofacial skeleton

The type of fixation (rigid skeletal vs. wire) was assessed against embryologic origin (membranous vs. endochondral) and recipient site (depository vs. resorptive) as variables affecting inlay and onlay bone-graft survival in 20 mature dogs. Wet weight and volume measurements were made at operation and at sacrifice (16 weeks). The results were as follows: (1) Rigid skeletal fixation increased bone-graft volume survival over wire fixation (p less than 0.05). (2) Fixation (i.e., rigid skeletal) and embryologic origin (i.e., membranous) were equal determinants of bone-graft volume survival (p less than 0.001); the recipient site was not significant for onlay bone graft survival. (3) Embryologic origin was the only significant determinant of weight survival (p less than 0.001). (4) Inlay bone grafts demonstrated greater weight and volume survival than onlay bone grafts (p less than 0.05). (5) Histologic and microradiographic studies demonstrated bony union of bone grafts fixed with rigid skeletal fixation, while fibrous union predominated in bone grafts fixed with wire technique.     

Three-dimensional model of the human craniofacial skeleton: method and preliminary results using finite element analysis

The purpose of this study was to develop a three-dimensional finite element model of the craniofacial skeleton using a dry human skull. The model consisted of 2918 nodes and 1776 solid elements, and was used to investigate the biomechanical effect of a distally directed orthopaedic force on the craniofacial complex. The force was applied at the level of the maxillary first molar. The results indicated that in response to the force system applied: the nasomaxillary complex displaces in a backward and downward direction and rotates in clockwise sense; the nasomaxillary complex, including the zygomatic bone, experiences high stress levels in comparison with those at the remaining bones; the stress distribution in the maxillary basal bone area is relatively uniform; and the stress distribution across the opposing surface of the bony margins of the sutures is non-uniform.     

An experimental study on the effect of rigid fixation on the developing craniofacial skeleton

Rigid fixation of the craniofacial skeleton has proven of great value in adult orthognathic and traumatic reconstructive surgical procedures. This technique has gained increased acceptance in the surgical treatment of infants and young children with congenital malformations, despite the fact that its effects on subsequent craniofacial growth are unknown. To examine this question, an experimental model using 25 young kittens was developed to compare rigid fixation with conventional wire fixation, with and without osteotomy. Our findings demonstrate a regional restriction of growth in the developing craniofacial skeleton when both wire and plate and screw fixation are utilized in concert with osteotomy. Further, a compensatory growth was observed in individual animals when plate fixation was utilized that was not seen in the wire-treated group. This suggests that there is a dynamic growth interaction between restriction and compensation in this setting.