Distraction osteogenesis of costochondral bone grafts in the mandible

Costochondral grafting for reconstruction of the Pruzansky type III mandible has given variable results. Lengthening of the rib graft by means of distraction had been advocated when subsequent growth of the grafted mandible is inadequate. This retrospective study reviews a series of patients with mandibular costochondral grafts who underwent subsequent distraction osteogenesis of the graft. A retrospective review identified two patient groups: group 1 consisted of individuals (n = 9) who underwent costochondral rib grafting of the mandible followed by distraction osteogenesis several months later at a rate of 1 mm/day. Group 2 consisted of patients with Pruzansky type II mandibles who had distraction osteogenesis without prior rib grafting (n = 9). The biomechanical parameters, orthodontic treatment regimens, and complications were examined versus patient age and quality of the rib graft. Distraction osteogenesis was successfully performed in six of the rib graft patients (group 1) and in all of the group 2 individuals. On the basis of the Haminishi scale, the computed tomographic scan appearance of the regenerate was classified as "standard or external" in six of the group 1 patients and as either "agenetic" or "pillar" (fibrous union) in the remaining three patients. In group 1, the average device was expanded 23 mm (range, 20 to 30 mm). Group 2 mandibular distraction results were all classified as either standard or external, and there was an average device expansion of 22.4 mm (range, 16 to 30 mm). The length of consolidation averaged 12.6 weeks in group 1, compared with 8.5 weeks in the traditional mandibular distraction patients (group 2). The mean shift of the dental midline to the contralateral side was 2.5 mm in group 1 versus 4.0 mm in group 2. Complex multiplanar and transport distractions were successfully performed on grafts of adequate bony volume. All four patients in group 1 with tracheostomies were successfully decannulated after consolidation. Rib graft distraction complications included pin tract infections in two patients, hardware failure with premature pin pullout in one patient, and evidence of fibrous nonunions in three young patients with single, diminutive rib grafts. In group 2, there were no distraction failures. Distraction osteogenesis can be successfully performed on costochondral rib grafts of the mandible; however, the complication rate is higher than in non-rib-graft patients. Performing the technique on older, more cooperative individuals seems to reduce this risk. In addition, placement of a double rib graft or an iliac bone graft of sufficient volume to create a neomandible with greater bone stock is an absolute requirement to decrease the risk of fibrous nonunion and provide a bone base of sufficient size for retention of the distraction device and manipulation of the regenerate.     

The effects of magnitude and frequency of distraction forces on tissue regeneration in distraction osteogenesis of the mandible.

Callus distraction has become an accepted treatment procedure to lengthen hypoplastic mandibles in humans. For this purpose, extraoral and intraoral devices have been applied successfully. The effects of the distraction vector, distractor stability, and rate and frequency of callus distraction on the regenerating tissues have been examined in various studies. In an experimental animal trial on pigs (n = 12), a newly developed microhydraulic osteodistractor was tested. The animals were evenly assigned to two groups to perform a continuous and noncontinuous osteodistraction of the mandible. Initially, the forces necessary to distract the pig mandibles were recorded from a noncontinuous distraction procedure; the results were then used to perform continuous bone distraction. Besides testing the new distractor, the study proved that in continuous osteodistraction, intramembranous bone regeneration occurred, whereas in noncontinuous osteodistraction the bone regeneration process followed a chondroid ossification. In continuous osteodistraction, the bone regeneration proceeded at a higher speed with the lower distraction forces compared with noncontinuous distraction, thereby reducing the consolidation period. Clinical and microscopical results are presented.     

Molecular signaling in bone fracture healing and distraction osteogenesis

The process of fracture healing has been described in detail in many histological studies. Recent work has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to the identification of many signaling molecules associated with the formation of skeletal tissues, including members of the transforming growth factor-beta (TGF-beta) superfamily and the insulin-like growth factor (IGF) family. Increasing evidence indicates that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and mineralization. Limb lengthening procedure (distraction osteogenesis) is a relevant model to investigate the in vivo correlation between mechanical stimulation and biological responses as the callus is stretched by a proper rate and rhythm of mechanical strain. This model also provides additional insights into the molecular and cellular events during bone fracture repair. TGF-beta 1 was significantly increased in both the distracted callus and the fracture callus. The increased level of TGF-beta 1, together with a low concentration of calcium and an enhanced level of collagen synthesis, was maintained in the distracted callus as long as mechanical strain was applied. Less mineralization is also associated with a low level of osteocalcin production. These observations provide further insights into the molecular basis for the cellular events during distraction osteogenesis.     

Expression of bone morphogenetic proteins during mandibular distraction osteogenesis

Distraction osteogenesis is a form of in vivo tissue engineering in which the gradual separation of cut bone edges results in the generation of new bone. In this study, the temporal and spatial expression of bone morphogenetic proteins (BMPs) 2, 4, and 7 was examined in a rabbit model of mandibular distraction osteogenesis. Fourteen skeletally mature male rabbits were studied. After osteotomy, a distractor was applied to one side of the mandible. After 1 week of latency, distraction was initiated at 0.25 mm every 12 hours for 3 weeks (distraction period), followed by a 3-week consolidation period. Two animals were killed each week after surgery. The generate bone was analyzed for the expression of BMP-2, -4, and -7 by using standard bone histological and immunohistochemical techniques. BMP-2 and -4 were highly expressed in osteoblastic cells during the distraction period and in chondrocytes during the consolidation period. BMP-7 demonstrated relatively minor expression in osteoblastic cells during the distraction period. All BMPs were strongly expressed in vascularized connective tissue during the distraction period. These data indicate that BMPs participate in the translation of mechanical stimuli into a biological response during mandibular distraction osteogenesis.     

Validation of a musculo-skeletal model of the mandible and its application to mandibular distraction osteogenesis

Mandibular distraction osteogenesis will lead to a change in muscle coordination and load transfer to the temporomandibular joints (TMJ). The objective of this work is to present and validate a rigid-body musculo-skeletal model of the mandible based on inverse dynamics for calculation of the muscle activations, muscle forces and TMJ reaction forces for different types of clenching tasks and dynamic tasks. This approach is validated on a symmetric mandible model and an application will be presented where the TMJ reaction forces during unilateral clenching are estimated for a virtual distraction patient with a shortened left ramus. The mandible model consists of 2 rigid segments and has 4 degrees-of-freedom. The model was equipped with 24 hill-type musculotendon actuators. During the validation experiment one subject was asked to do several tasks while measuring EMG activity, bite force and kinematics. The bite force and kinematics were used as input for the simulations of the same tasks after which the estimated muscle activities were compared with the measured muscle activities. This resulted in an average correlation coefficient of 0.580 and an average of the Mean Absolute Error of 0.109. The virtual distraction model showed a large difference in the TMJ reaction forces between left and right compared with the symmetric model for the same loading case. The present work is a step in the direction of building patient-specific mandible models, which can assess the mechanical effects on the TMJ before mandibular distraction osteogenesis surgery.     

Distraction osteogenesis of the porcine mandible: histomorphometric evaluation of bone

Distraction osteogenesis is a technique for skeletal lengthening that exploits the body's innate capacity for bone formation in response to tension forces on the repair callus. The authors developed a distraction osteogenesis model with a semiburied device in the Yucatan minipig mandible because of similarities between human and porcine mandibular anatomy, temporomandibular function, chewing patterns, and bone turnover rates. The purpose of this study was to measure histomorphometric bone fill after different latency periods, rates of distraction, and duration of neutral fixation in the minipig mandible. In addition, the relationship between histomorphometric bone fill and clinical stability was investigated. Mandibular osteotomies in 20 female Yucatan minipigs weighing 25 to 30 kg were distracted with modified semiburied distraction devices. Variables included 0-day or 4-day latency; 1-mm, 2-mm, or 4-mm daily distraction rates; gap size of 7 or 12 mm; and evaluation after neutral fixation for various lengths of time. Specimens were fixed in 2% paraformaldehyde, pH 7.4, before being embedded in methylmethacrylate. Sections were prepared from the region just below the inferior alveolar canal. The area of new bone formation within the gap was measured and expressed as a percentage of the total area of the distraction gap. Bone fill ranged from 0 to 100 percent. A pilot study with 7-mm advancements showed similar bone fill with 0-day or 4-day latency, but with poor reproducibility. Mandibles that were distracted to 12 mm at 1 mm per day exhibited nearly complete bone fill, either with 0-day latency (average, 93 percent) or 4-day latency (average, 100 percent). Mandibles that had been distracted for 3 days at 4 mm per day showed moderate osteogenesis and clinical stability with increasing time of neutral fixation. Bone fill was significantly correlated with clinical stability (Spearman r = 0.801, p = 0.001). Histological examination showed exuberant periosteal osteogenesis in distracted mandibles, even in those that showed poor bone fill and clinical stability. Thus, the periosteum appears to be a major source of new bone formation. These results show that osteogenesis was nearly complete with 1 mm per day and 0-day or 4-day latency. These results are consistent with the authors' previously reported clinical and radiographic observations that a latency period is not necessary for successful healing of the mandibular distraction osteogenesis wound.     

Characterization of midface maxillary membranous bone formation during distraction osteogenesis

The purpose of the study was to follow the early events in bone formation and neovascularization during maxillary distraction and after the consolidation period and to define the characterization of the new bone in the distracted area. Maxillary osteotomy was performed in seven sheep. In five animals, an external distraction device was used for maxillary lengthening of 20 mm at a rate of 1 mm/day for 20 days. Another two animals served as controls without distraction. Sequential biopsies were performed. The methods used for analysis were histologic, immunohistochemical, and ultrastructural by transmission electron microscopy. During the 5 days of latency, a fibrin clot was formed that after 5 days of distraction was replaced by granulation tissue, proliferating mesenchyme-like cells, and capillaries. After 10 days of distraction, the regenerated tissue could be divided into three main zones and two transitional areas: a central zone occupied by many polygonal mesenchyme-like cells and spindle-shaped cells that proliferated intensively; two paracentral zones on both sides of the central zone in which many cells showed morphologic signs of apoptosis leading to a decreased number of fibroblast-like cells embedded in wavy collagen fibers; a transitional area from the central to the paracentral zone in which concentric cellular colonies were believed to represent a novel form of vasculogenesis; distal-proximal zones, located on both sides of the paracentral zones and in continuation with the old bone, showed delicate new woven bone trabeculae that grew continuously in the direction of lengthening and gradually became mineralized; and a transitional area from the paracentral to the distal-proximal zones in which there was recruitment of preosteoblasts from the distracted tissue to the trabecular tips. These further differentiated into osteoblasts that contributed to the trabecular growth. The histologic feature pattern was similar after 15 and 20 days of continuous distraction. At the end of lengthening, after 20 days, delicate longitudinally oriented trabeculae continued to grow by recruiting preosteogenic cells from the central distracted tissue, became mineralized, and were rimmed by osteoblasts. After 6 weeks of retention, the trabeculae thickened and consisted of a mixture of lamellar and woven bone. In conclusion, the distraction force creates a pool of undifferentiated mesenchyme-like cells with osteogenic potential and triggers capillary formation, a clear zonation can be observed during active lengthening, and new bone trabeculae begin to form between 5 and 10 days after distraction, soon become aligned with osteoblasts, and continue to grow as long as distraction force is applied. This characterization may help in any exogenous involvement with growth factors to improve bone quality.     

Effect of distraction osteogenesis of the mandible on upper airway volume and resistance in children with micrognathia

Children with craniofacial anomalies often have compromise of the upper airway, a condition with potential for morbidity and mortality. In children with microretrognathia, the diminutive size and retruded position of the mandible reduces the size of the oropharynx, thereby predisposing to glossoptosis and airway obstruction. Although several authors have reported successful use of mandibular distraction osteogenesis to alleviate this type of upper airway obstruction, the physiologic relationship between changes in mandibular shape, size, and position and upper airway dynamics remains undefined. The purpose of this study was to develop methodologies to quantitatively evaluate upper airway dynamics in children with micrognathia both before and after mandibular distraction osteogenesis. The patient population consisted of four children with micrognathia who had successfully undergone upper airway stabilization by bilateral mandibular distraction osteogenesis. The data used were digitally archived computed tomographic scan data from high-resolution, thin-slice head computed tomographic scans obtained before and after mandibular distraction. Upper airway evaluation was performed in two ways: static and dynamic. Static analysis consisted of computer quantification of predistraction and postdistraction mandibular and upper airway volumes using Analyze imaging software. Dynamic analysis consisted of fabrication of rigid stereolithographic hollow cast models of the upper airway produced from computed tomographic scan data. Models were used for characterization of upper airway resistance and flow patterns as related to respiration. After distraction osteogenesis, mandibular total volume increased 32, 32, 18, and 25 percent (mean, 27 percent) and upper airway volume increased by 20, 31, 23, and 71 percent (mean, 37 percent). A significant decrease in flow resistance, both inspiratory and expiratory, was observed in the patient with the greatest upper airway volume increase (71 percent) after distraction. After distraction, the inspiratory resistance was diminished by 51 percent and the expiratory resistance diminished by 85 percent. However, the three patients with more modest upper airway volume increases of 20 to 31 percent demonstrated no statistically significant change in flow resistance after distraction. Results of this study support the conclusion that distraction osteogenesis of the micrognathic mandible increases the volume of the upper airway, roughly paralleling the increase in mandibular volume. In the biomechanical airway model studied, upper airway volume expansion has been shown to be able to decrease the flow resistance over the length of the airway, presumably secondary to an increase in the average cross-sectional area. The artificial rigidity of the stereolithographic "airway" compared with the elasticity of the human upper airway may account for the insensitivity of this model to smaller but clinically significant airway changes.     

Modeling distraction osteogenesis: analysis of the distraction rate

Distraction osteogenesis is a useful technique aimed at inducing bone formation in widespread clinical applications. One of the most important factors that conditions the success of bone regeneration is the distraction rate. Since the mechanical environment around the osteotomy site is one of the main factors that affects both quantity and quality of the regenerated bone, we have focused on analyzing how the distraction rate influences on the mechanical conditions and tissue regeneration. Therefore, the aim of the present work is to explore the potential of a mathematical algorithm to simulate clinically observed distraction rate related phenomena that occur during distraction osteogenesis. Improvements have been performed on a previous model (Gómez-Benito et al. in J Theor Biol 235:105–119, 2005) in order to take into account the load history. The results obtained concur with experimental findings: a slow distraction rate results in premature bony union, whereas a fast rate results in a fibrous union. Tension forces in the interfragmentary gap tissue have also been estimated and successfully compared with experimental measurements.     

Callus stimulation in distraction osteogenesis

Distraction osteogenesis has been described as in vivo tissue engineering. The ability to stimulate this process for the repair of bony defects or lengthening of congenitally shortened facial structures is likely to significantly impact the field of craniofacial surgery. The purpose of this study was to determine whether mechanical stimulation of the distracted rabbit mandible would accelerate the maturation of the bony callus when applied during the early consolidation period. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A uni-directional internal distractor device (Synthes, Paoli, Pa.) was positioned along a plane perpendicular to the line of osteotomy. After a 7-day latency period, distraction was commenced at a rate of 1.0 mm/day for 12 days in all animals. In a control group of 10 rabbits, a consolidation period of 8 weeks was observed before they were killed. In the experimental group of 10 rabbits, daily alternate compression and distraction of 1 mm (sequential compression and distraction) was performed for 3 weeks followed by a 5-week period of rigid fixation. Each animal received a dose of a fluorescent label at three different time points during the study: at the end of the distraction period, 3 weeks after the completion of the distraction phase, and 3 days before it was killed. All animals were killed 8 weeks after the completion of the distraction phase. Undecalcified histologic analysis and 3-point bending tests to failure were performed on the extracted mandibles. The results of the experimental and control groups were compared.Four animals in the control group and three animals in the experimental group were excluded from the study because of screw loosening resulting in distractor dislodgment or because of infection. On histologic analysis, cortical thickness at the center of the callus was found to be significantly greater in the experimental group compared with the control group when normalized to the contralateral hemimandible (83 percent versus 49 percent, respectively; p < 0.007). The ratio of cortical to cancellous bone in the distracted callus was uniformly found to be greater in the experimental specimens. The mineral apposition rate was calculated by using fluorescence microscopy and found to be significantly greater in the experimental group both during the period of sequential compression and distraction (3.2 microm/day versus 2.1 microm/day, p = 0.02) and after the period of sequential compression and distraction (1.4 microm/day versus 1.1 microm/day, p = 0.006). Mechanical testing revealed no significant differences in bending strength or stiffness between experimental or control groups (p = 0.54 and 0.47, respectively). This study has demonstrated that daily alternating compression and distraction of 1 mm amplitude during the early consolidation period has a stimulatory impact on callus formation with respect to osteoblastic activity, remodeling, and maturation of bone. Optimal timing and amplitude of sequential movement, long-term biomechanical differences, and molecular pathways have yet to be elucidated.     

Immunohistochemical localization of bone morphogenetic protein-signaling Smads during long-bone distraction osteogenesis.

In this study we investigated the expression of bone morphogenetic protein (BMP)-signaling Smads in distraction osteogenesis (DO). Osteotomy of the right tibia was performed in 14 skeletally mature white New Zealand male rabbits. Lengthening was started 1 week later at a rate of 0.5 mm/12 hr and was maintained for 3 weeks. Expression of Smad proteins 1, 4, 5, 6, 7, and 8 and Smad ubiquitin regulatory factors (Smurfs) 1 and 2 was evaluated in the distracted zone using immunohistochemistry. Expression of receptor-regulated Smads (R-Smads) 1, 5, and 8 showed a significant increase during the distraction phase, followed by a gradual decrease during the consolidation phase. Smad 4 showed significant expression during both distraction and the beginning of the consolidation phase. Smad 6 and Smad 7 were highly expressed during the consolidation phase. Staining for both Smurfs 1 and 2 was maximal at the end of the distraction period. Staining for all proteins was most intense in chondrocyte and fibroblast-like cells. Expression pattern of R-Smads correlated with our previously reported expression pattern of BMPs 2, 4, and 7 and their receptors. These results therefore suggest a role for the whole BMP signaling pathway including the Smad proteins in DO.     

Volumetric change of the medial pterygoid following distraction osteogenesis of the mandible: an example of the associated soft-tissue changes

Mandibular distraction osteogenesis lengthens not only the affected skeleton but also the associated muscles of mastication. The purpose of this study was to determine medial pterygoid volume before and after distraction by using computed tomography. Using computed tomographic scans, the volume of the medial pterygoid muscle was determined before and after mandibular distraction in six pediatric patients. In four unilateral distraction patients (average age, 65 months), the average increase of the medial pterygoid muscle on the distracted side of the mandible was 29 percent, and on the contralateral nondistracted side, 10 percent. The average increase in medial pterygoid muscle volume in two bilateral distraction patients (each aged 8 months) was 75 percent. Results of this study demonstrate that distraction osteogenesis of the human mandible not only lengthens deficient bone, but it also increases the volume of the attached musculature.     

Computer planning for distraction osteogenesis

Distraction osteogenesis of the mandible has found an application in the treatment of patients with a variety of different mandibular deformities. Compared with the relatively simple unidirectional distraction of long bones as described by Ilizarov, the three-dimensional distraction of the mandible is extremely complex. Whereas experience with orthognathic surgery clearly demonstrates that careful presurgical planning is necessary to achieve predictable outcomes, there are few reported methods for the planning of mandibular distraction. The authors have developed a method for planning distraction osteogenesis of the mandible that involves the use of three-dimensional modeling and animation to simulate distraction osteogenesis in virtual reality. The first step in the authors' treatment planning process is to obtain a three-dimensional computerized scan of the facial skeleton. From this scan, a three-dimensional wire-mesh model is built using animation software. With the same software, a virtual distractor is built and installed on the wire-mesh model. The osteotomies and the distraction process are then simulated. Finally, a recipe for sequencing the linear and angular changes of the distractor is calculated. The authors have used this planning process in seven patients (age range, 4 to 10 years): four with unilateral mandibular deformities and three with bilateral. The planning process has yielded predictable and reproducible results.