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Expression of neurotrophins and their receptors tropomyosin-related kinases (Trk) under tension-stress during distraction osteogenesis.

The localization and expression of neurotrophins and their receptors during distraction osteogenesis was investigated in 72 male rat femurs (11 weeks old) to further clarify the concurrence of cellular and molecular events of new bone formation. After osteotomy, a 7-day lag phase was followed by distraction at the rate of 0.25 mm/12 h for 21 days (distraction phase), and a 7-day consolidation phase. The localization of neurotrophins (NGF, BDNF and NT-3) and their receptors tropomyosinrelated kinases (TRKA, TRKB and TRKC) by immunostaining showed positive staining in bone forming cells in each stage, although the presence and staining intensity varied by cell type and phase. The expressions of NGF, BDNF and NT-3 by real-time polymerase chain reaction (real-time PCR) showed that the peak of the mRNA expression of NGF occurred 10 days after distraction. NT-3 increased during bone extension, but decreased when distraction stopped. In contrast, BDNF continued to increase gradually throughout the distraction and consolidation phases. These findings suggest that neurotrophins and their receptors may play different roles in endochondral and intramembranous ossification in distraction osteogenesis. The tension stress caused by distraction may stimulate the expression of neurotrophins and their receptors, and promote osteogenesis.

Animals↗

Vertical distraction osteogenesis of the mandible applied to an iliac crest graft: report of a case.

OBJECTIVES: This clinical case represents a particular application of vertical distraction osteogenesis of the mandible. The surgical technique was applied to an iliac crest bone graft previously positioned on an anterior mandibular defect with the aim to restore the vertical height after a partial resorption in a trauma patient. CASE REPORT: Distraction osteogenesis was applied because it was necessary to restore the mandibular height in a young male patient who presented with a post-trauma anterior mandibular bony deficiency. Because of the irregularity of the mandibular surface and the depth of the defect, the patient first underwent an iliac crest bone grafting that, after 3 months, showed partial resorption. Vertical distraction osteogenesis was performed on the grafted mandible in order to obtain a satisfactory bony height of the mandibular ridge. Then the patient was successfully rehabilitated by means of an implant-supported prosthesis. CONCLUSION: Vertical distraction osteogenesis appears to be a versatile surgical procedure, which can be applied as a secondary treatment in patients presenting with mandibular trauma sequelae.

Adult↗

"Pumping the regenerate": an evaluation of oscillating distraction osteogenesis in the rodent mandible.

Mandibular distraction osteogenesis (DO) has become an important technique to lengthen the hypoplastic mandible and to reconstruct osseous defects after ablative surgery. The hallmark of successful DO is the creation of new bone within the distraction gap. Several anecdotal reports have described alternating compressing and lengthening protocols (i.e., "pumping the regenerate") to augment regenerate bone formation. The purpose of this experiment was to analyze formally the effects of an alternating compression/distraction protocol with a traditional distraction protocol. Ten adult male rats underwent unilateral mandibular osteotomy with placement of a custom distractor. After a latency period of 5 days, distraction was initiated at a rate of 0.25 mm twice daily. Animals in the control group (N = 5) were distracted to a length of 5.0 mm for 10 days at a rate of 0.25 mm twice daily. In contrast, animals in the experimental group (N = 5) were distracted to a length of 2.5 mm (at a rate of 0.25 mm twice daily) for 5 days, then compressed 1.0 mm for a 2-day period, and redistracted to a length of 5.0 mm. Regenerate cross-sectional area was evaluated by computed tomography performed after 5 weeks of consolidation. Gross examination and histological analysis were performed by a panel of experienced reviewers. Radiological as well as histological analysis of regenerate cross-sectional area demonstrated no significant differences between experimental (i.e., "pumped") and control groups. Both groups demonstrated excellent regenerate bone formation with no evidence of fibrous union. This study represents the first attempt to investigate the anecdotal technique of pumping the mandibular regenerate. The authors have demonstrated that pumping the regenerate leads to no substantial differences in radiological or histological appearance of regenerate bone formation.

Animals↗

Distraction osteogenesis for segmental bone defect. Physeal change after acute bone shortening followed by gradual lengthening in a rabbit tibia model.

We investigated physeal change after acute bone shortening followed by distraction osteogenesis in a rabbit tibia model. Distraction osteogenesis was performed on acutely shortened right rabbit tibia after removing a diaphyseal segment until distraction reached the length of the excised segment. Sixty animals were divided into three groups (n=20) according to the amount of shortening (20, 30, and 40% of original length) and radiographic, immunohistochemical, and histomorphometric analyses were performed to evaluate the physeal activity. The results showed no differences between groups and all animals could recover the original length without growth retardation. There was no notable venous congestion or lymphatic kinking associated with acute shortening. These results suggest that distraction osteogenesis at the primary site of shortening may have little adverse effects on the growth plate, when the shortening can provide sufficient soft tissue without vascular compromise and the amount of lengthening does not exceed that of shortening.

Animals↗

Systemic regulation of angiogenesis and matrix degradation in bone regeneration--distraction osteogenesis compared to rigid fracture healing.

Aim of this study was the investigation of systemic biochemical regulation mechanisms of bone regeneration by angiogenic and matrix-degrading enzymes during distraction osteogenesis compared to rigid osteotomy bone healing. Serum samples of 10 otherwise healthy patients with callus distraction for lower limb-lengthening and 10 osteotomy patients undergoing elective axis correction have been collected prospectively in a standardized time schedule before and up to 6 months after the procedure. At the end of the individual investigation period, concentrations of metalloproteinases (MMP-9, -13), tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and the angiogenic factors angiogenin and VEGF have been detected by use of commercially available enzyme immunoassays. Results have been compared to our preliminary study on proMMP-1-3. In distraction osteogenesis, significantly elevated serum concentrations compared to baseline could be detected postoperatively for proMMP-1, MMP-9, TIMP-1, angiogenin and VEGF but not for proMMP-2, proMMP-3 or TIMP-2. In patients with rigid osteotomy healing, MMP-9, TIMP-1, TIMP-2, angiogenin and VEGF were significantly increased respectively. Comparison of both patient collectives revealed significantly higher increases of serum proMMP-1, VEGF and TIMP-1 in distraction patients during the lengthening period and significantly higher serum concentrations of TIMP-2 in late fracture healing period in osteotomy patients. Serum levels of MMP-13 were below the lowest standards, and therefore quantitative analysis was not possible. Bone regeneration in distraction osteogenesis and rigid osteotomy healing is accompanied by systemic increase of matrix-degrading and angiogenic factors in a certain time course and quantity. This might reflect biochemical regulation of local bone healing in the circulation. ProMMP-1, VEGF and TIMP-1 seem to be key regulatory factors during distraction osteogenesis.

Adult↗

Alveolar distraction osteogenesis before placement of dental implants.

Distraction osteogenesis of the edentulous alveolar ridges may be considered an alternative to many other augmentation oriented surgical techniques. It is now being widely used for treating severe forms of alveolar ridge atrophy, especially before the placement of dental implants. Leibinger Endosseous Alveolar Distraction System (LEAD; Stryker Leibinger, Kalamazoo, MI) is an intraosseous distraction device used for edentulous ridges. In this study, the healing was uneventful in all 5 cases that were treated except 1, in which the vitality of the distraction segment could not be maintained. No complications related to the prosthodontic restoration were observed.

Adolescent↗

Midface membranous bone lengthening: A one-year histological and morphological follow-up of distraction osteogenesis.

Midface bone lengthening was performed on three young, adult sheep using distraction osteogenesis following osteotomy of the maxilla and mounting of an extraoral fixation device. The midface was gradually distracted, 2 mm/day, for 21 days, up to approximately 40 mm. A marked midface advancement was noted. Following a further 6 weeks of retention, the device was removed and the animals were followed for 1 year. Biopsies specimens were taken from the distracted area at the end of the distraction period, after the additional 6 weeks of retention, and finally 1 year later. A nondistracted area of the maxillary bone served as control. The specimens were analyzed histologically, histochemically, and by scanning electron microscopy for the ultrastructural pattern, mineralization, mineral content, and approximate Ca2+ concentration. Clinically and radiographically, all sheep fully bridged the experimental gap. Histologically, at the completion of distraction, collagen bundles and slender bone trabeculae oriented in the direction of the distraction could be seen. At the end of the retention period, the trabeculae thickened noticeably and were partially replaced by mature lamellar bone. At the end of 1 year and after completion of the process of remodeling, the pattern of the distracted area resembled the control area. The mineralization, as reflected by quantitative calcium analysis, compared with the nondistracted area, demonstrated a low rate of mineralization after 3 weeks of lengthening, increased 6 weeks later, and after 1 year became nearly the same as in the nondistracted area. In conclusion, distraction osteogenesis provides satisfactory quantitative and structural new bone.

Animals↗

[Distraction osteogenesis for hypoplastic facial bones].

Distraction osteogenesis is a well-known method for bone lengthening which stretches callus to generate new bone in the distracted area. The method was developed by Ilizarov for the lengthening of long enchondral bones. In recent years the method has also been applied to the facial bones and to the jaw.

Adolescent↗

Effect of recombinant human tissue inhibitor of matrix metalloproteinase-1 in mandibular distraction osteogenesis in rabbits: a computed tomographic study.

Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), are responsible for the controlled degradation of collagen in bone. We studied the long-term stability of the regenerated bone formed by distraction osteogenesis, and the effect of recombinant human TIMP-1 on the remodelling of bone formed by mandibular distraction osteogenesis in rabbits. Nine rabbits were subjected to distraction osteogenesis of the mandible and divided into three groups: a control group with no collagen implanted; a sham-control group with a collagen sheet implanted; and an experimental group with a collagen sheet impregnated with rhTIMP-1 implanted. Computed tomograms were taken at weeks 4, 12, and 24 after distraction, and micro-computed tomograms and histological examinations were made at week 24. There was no significant resorption of regenerated bone at the site of distraction in any group after 6 months of consolidation, suggesting that the regenerated bone formed by distraction osteogenesis is stable. We found no obvious influence of rhTIMP-1 in the collagen sheet on the bony regenerate after 6 months of consolidation.

Animals↗

Longitudinal cephalometric analysis after maxillary distraction osteogenesis.

The aim of this study was to analyze the long-term dentoskeletal changes in patients who received distraction osteogenesis of the maxilla. Seventeen patients aged 12 to 31 years underwent rigid external distraction osteogenesis for treatment of maxillary hypoplasia. Cephalograms were evaluated retrospectively regarding linear and angular measurements. Follow-up times ranged from 1 to 5 years. In two patients, there was no consolidation of the Le Fort I segment to the midface. After the 0- to 12-month period, the maxilla had a stable position in all patients. Nevertheless, there was further decrease of SNA and ANB and an increase of the facial concavity thereafter. Ongoing growth of the facial skeleton must be considered when distraction osteogenesis is chosen for the advancement of the maxilla in adolescents.

Adolescent↗

[Distraction osteogenesis as treatment for craniofacial deformities].

Distraction osteogenesis is a surgical technique for treating different craniofacial deformities. The sophisticated clinical expression of craniosynosotosis in the face, as well as in the skull can be corrected using different osteotomies, in which we can include the frontal bone, orbits, the malar bones and the maxillae. Once the osteotomy has been completed, we can use the distraction devices to achieve the planned bone advancement. This procedure can be also performed with endoscopic techniques producing less morbidity, with minimal complications, simultaneously producing a highly satisfactory correction of the frontal deformity, the exorbitismus, the malar and the mid-face retrusion in these patients. As the distraction procedure is gradual, soft tissues resistance against the advancement can be easily superated achieving larger antero-posterior bone advancement that can vary between 16 to 32 mm in the frontal area and between 9 to 16 mm in the maxillae. The new position of the bones are maintained in place for new bone formation areas over the osteotomy lines. The aesthetic and functional changes after the procedure have been highly satisfactory in these patients.

Child↗

Distraction osteogenesis of the mandible for airway obstruction in children.

OBJECTIVES: Objectives of the study were to determine the effectiveness of distraction osteogenesis of the mandible to relieve airway obstruction in children with tongue-base airway obstruction and to describe the new surgical techniques developed for use in infants and young children. STUDY DESIGN: Prospective, nonrandomized study. METHODS: Analysis of 11 children with severe airway obstruction secondary to tongue-base obstruction was performed. Patients were between 2 weeks and 5.5 years of age. All patients underwent distraction osteogenesis of the mandible. RESULTS: Twelve distraction procedures in the 11 children in the study were accomplished; decannulation or extubation was successful in all children. CONCLUSION: Distraction osteogenesis of the mandible can be used to treat tongue-base airway obstruction in appropriately selected children.

Age Factors↗

Mandibular alveolar ridge augmentation in the dog using distraction osteogenesis.

PURPOSE: This study investigated the use of distraction osteogenesis for alveolar ridge augmentation. MATERIALS AND METHODS: Four dogs each had two superior and two inferior implants placed horizontally into an edentulous mandibular quadrant and, after integration, a distraction device was applied. An osteotomy was made to allow the ridge to be distracted vertically. After 10 mm vertical distraction, the device was stabilized. RESULTS: The vertical augmentation averaged 8.85 +/- 1.05 mm after 10 weeks of healing. Serial sections showed that bone had formed between the distracted segments, creating an augmented ridge. CONCLUSIONS: Distraction osteogenesis has the potential for use in augmentation of the alveolar ridge.

Alveolar Ridge Augmentation↗

Effect of distraction osteogenesis on the peripheral nerve: experimental study in the rat.

Distraction osteogenesis is the current method of choice for bone lengthening. Despite the gain in experience, various complications are reported, among them, adverse effects on peripheral-nerve function. In order to thoroughly investigate the effect of distraction on neural tissue, a distraction osteogenesis model in the rat was established, using the femur of 30 Sprague-Dawley rats. The animals were randomized in three groups, following different rates of distraction (0.5 mm, 1.0 mm, and 1.5 mm/day) for 50, 25, and 16 days, respectively, so that the final length of distraction was the same in all groups. The mean sciatic function index ranged near normal in all groups. All groups demonstrated decrease of conduction velocity and the area under the curve of the compound action potential, while morphologic alterations consisted of decrease in the number of axons and evidence of active degeneration. Animals in Groups 1 (0.5 mm/day) and 2 (1 mm/day) displayed comparable changes, while in Group 3 animals (1.5 mm/day), changes were significantly more adversely dramatic. The safest and fastest rate of distraction in this rat model was determined to be 1 mm/day.

Action Potentials↗

[CT-assisted volumetry and densitometry of distraction osteogenesis lengthened mandibular areas].

Gradual callus distraction in the correction of hypoplastic areas in the viscerocranial skeleton is an established method due to its efficacy. Whereas functional and esthetical improvements can be seen easily, it is impossible to get the increase of the bony mass right using the distractor scale or by clinical investigation. Only in animal studies can volumetric and densitometric measurements be done directly. By permission of the local ethics commission, in a clinical study, CT data of 24 children (12 unilateral and bilateral hypoplasias each) taken before and after mandibular distraction osteogenesis were used to get information on the amount of created bone and the grade of ossification of the callus at the time of the distractor removal. The CT data were prepared for computer evaluation using software which had been especially developed for this investigation. The quality of the investigation was influenced by disturbed data acquisition (insufficient sedation, Gantry deviation, different axial cuts). Therefore, the estimation of the real increase of bone was not possible, but all in all an increase of the volume could be seen. Using a grey scale analysis, the grade of new bone ossification was over 90% at the time of distractor removal. In our opinion, these results argue against the use of CT scans for the validation of a mandibular distraction. The estimation of the volume is very imprecise, the grade of ossification of the new bone very constant.

Absorptiometry, Photon↗

Changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible.

PURPOSE: Distraction osteogenesis (DO) is a commonly used technique for mandibular lengthening, but changes in the temporomandibular joint have not been well documented. The purpose of this study was to evaluate the effect of DO, at varying rates, on the mandibular condyle and articular disc. MATERIALS AND METHODS: Semiburied distractors were placed via submandibular incisions in 15 minipigs. Two unoperated animals served as controls. The protocol consisted of 0 day latency and rates of 1, 2, or 4 mm/d for a 12-mm gap. After the animals were killed (0, 24, or 90 days), ipsilateral and contralateral condyles and discs were harvested and evaluated to determine changes in 1) condylar form and size, 2) condylar surface, and 3) the articular disc. RESULTS: Articular surfaces of the condyles in control animals were smooth, with no irregularities or erosions. In animals undergoing distraction, ipsilateral condyles showed increasing changes in morphology and AP dimension, and surface contour irregularities as the DO rate increased. These changes were present, but to a lesser degree, in the contralateral condyles. Articular discs of both ipsilateral and contralateral sides showed variable thinning at the medial aspect at end DO. After 90 days, changes in the condyles and discs were reduced by remodeling except in the 4 mm/d DO groups. CONCLUSIONS: Results of this preliminary study indicate that gross changes occur in condyles and discs after unilateral mandibular DO. These changes are more severe at faster distraction rates (4 mm/d) and tend to resolve during neutral fixation when a rate of 1 mm/d is used.

Adaptation, Physiological↗

New fixation method for maxillary distraction osteogenesis using locking attachments.

PURPOSE: The external traction hooks of the intraoral splint used in the rigid external distraction (RED) system for maxillary distraction osteogenesis interfere with the surgical procedures. The purpose of this study is to introduce an innovative splint fixation method for maxillary distraction osteogenesis with Locking Attachments and evaluate their advantages, such as reduction of operating time compared with the traditional intraoral splint method. PATIENTS AND METHODS: Retrospective comparison of operative times of maxillary Le Fort I osteotomy procedures was carried out with the traditional protocol using the intraoral splint cemented to the maxillary dentition (n = 14), and a removable intraoral splint that is inserted postsurgically (n = 14). Operative procedure times were compared and analyzed statistically using the data extracted from the surgical records. RESULTS: There were no complications inserting the removable splint postsurgically, including pain, discomfort, or time-consuming procedure. Stable and secure splint fixation was obtained before the distraction procedure and the desired treatment goals were obtained in all patients. The total operative procedure times were significantly reduced in the Locking Attachments group by 24% to 41% (approximately 65 minutes) compared with earlier operations involving the conventional splints (P < .05). CONCLUSIONS: Maxillary distraction osteogenesis with the Locking Attachments is a highly effective fixation approach to manage severe hypoplastic maxilla, eliminating lip constraints resulting from scarring and allowing for easier, more deliberate and careful dissection. The use of the Locking Attachments is reliable in craniofacial surgery and has proved to be advantageous in the reduction of the operating time and surgical risks.

Adolescent↗

Three modes of ossification during distraction osteogenesis in the rat.

We developed a rat model of limb lengthening to study the basic mechanism of distraction osteogenesis, using a small monolateral external fixator. In 11-week-old male rats we performed a subperiosteal osteotomy in the midshaft of the femur with distraction at 0.25 mm every 12 hours from seven days after operation. Radiological and histological examinations showed a growth zone of constant thickness in the middle of the lengthened segment, with formation of new bone at its proximal and distal ends. Osteogenic cells were arranged longitudinally along the tension vector showing the origin and the fate of individual cells in a single section. Typical endochondral bone formation was prominent in the early stage of distraction, but intramembraneous bone formation became the predominant mechanism of ossification at later stages. We also showed a third mechanism of ossification, 'transchondroid bone formation'. Chondroid bone, a tissue intermediate between bone and cartilage, was formed directly by chondrocyte-like cells, with transition from fibrous tissue to bone occurring gradually and consecutively without capillary invasion. In situ hybridisation using digoxigenin-11-UTP-labelled complementary RNAs showed that the chondroid bone cells temporarily expressed type-II collagen mRNA. They did not show the classical morphological characteristics of chondrocytes, but were assumed to be young chondrocytes undergoing further differentiation into bone-forming cells. We found at least three different modes of ossification during bone lengthening by distraction osteogenesis. We believe that this is the first report of such a rat model, and have shown the validity of in situ hybridisation techniques for the study of the cellular and molecular mechanisms involved in distraction osteogenesis.

Animals↗