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Callus formation enhanced by BMP-7 ex vivo gene therapy during distraction osteogenesis in rats.

This study was designed to observe the effects of bone morphogenetic protein-7 (BMP-7) ex vivo gene therapy on callus formation during rat mandibular distraction osteogenesis (DO). Fifty-four Sprague-Dawley rats underwent osteodistraction of the right mandible and were then randomly divided into three groups. Immediately after distraction, autologous bone marrow mesenchymal stem cells (MSCs) transfected with BMP-7, MSCs untransfected with BMP-7, and physiological saline were injected into the distraction gaps of the mandibles in groups A, B, and C, respectively. Nine animals from each group were euthanized at 2 and 6 weeks after completion of distraction. The distracted mandibles were removed and processed for radiographic, histological, immunohistochemical, and scanning electron microscopic examinations as well as Ca/P ratio analysis. Group A animals showed greater bone formation and earlier mineralization in the distracted callus when compared with group B. Similarly increased callus formation was found in group B than group C. Positive immunostaining of BMP-7 was observed in the distracted callus in all groups. However, BMP-7 expression was much stronger in group A compared with groups B and C. The results of this study suggest that BMP-7-mediated ex vivo gene transfer based on MSCs may accelerate callus formation in distraction osteogenesis and facilitate consolidation. Local gene therapy may ultimately be an alternative or supplemental approach to DO enhancement, especially for patients whose osteogenic potentials are compromised by diseases such as osteoporosis, severe trauma, and postoncologic irradiation.

Animals↗

Interdental distraction osteogenesis and rapid orthodontic tooth movement: a novel approach to approximate a wide alveolar cleft or bony defect.

The closure of a wide alveolar cleft and fistula in cleft patients and the reconstruction of a maxillary dentoalveolar defect in traumatic patients are challenging for both orthodontists and surgeons. This is due to the difficulty in achieving complete closure by using local attached gingiva and the great volume of bone required for the graft. In this article, the authors propose using interdental distraction osteogenesis to create a segment of new alveolar bone and attached gingiva for the complete approximation of a wide alveolar cleft/fistula and the reconstruction of a maxillary dentoalveolar defect. They performed this procedure on one patient with a traumatic maxillary dentoalveolar defect and 10 patients with unilateral or bilateral cleft lips and palates who had varied dentoalveolar clefts/fistulas. Interdental and maxillary osteotomies were performed on one side of the dental arch by the cleft or defect. After a latency period of 3 days, the osteotomized distal segment of the dental arch was then distracted and transported toward the cleft or defect by using a toothborne intraoral distraction device. The alveoli and gingivae on both ends of the cleft or defect were approximated after distraction osteogenesis. The need for extensive alveolar bone grafting was eliminated. A segment of new edentulous alveolus and attached gingiva was created interdentally at a site distant to the cleft or defect. In the cleft patients, teeth were moved orthodontically into the regenerate (newly formed alveolar bone) dental crowding 1 week after distraction. The orthodontic tooth movement was rapidly completed in 3 months, and the edentulous space was eliminated. Interdental distraction osteogenesis minimizes an alveolar cleft/fistula and helps reconstruct a maxillary dentoalveolar defect by approximating the native alveoli and gingivae; it also creates new alveolar bone and gingiva for rapid orthodontic tooth movement.

Alveolar Process↗

Reconstruction of maxillectomy defect by transport distraction osteogenesis.

The study aimed to explore the feasibility of posterior maxillectomy reconstruction by transport distraction in a primate model. In each of 14 male adult rhesus monkeys, posterior partial maxillectomy was performed on one side of maxilla to create a posterior maxillary deflect. Immediately after the maxillectomy, a dentoalveolar segment anterior to the defect was osteotomized as transport segment and a custom-made transport distractor was fixed on the residual maxilla. After a latency period of 5 days, the distractor was activated 1 mm daily to move the transport segment backward to the defect. This process lasted about 2 weeks. The transport segment was allowed to consolidate and the animals were sacrificed at different defined intervals. Transport distraction was successful in six animals. Three other cases were completed with minor wound dehiscence and one had a small oro-antral fistula with subsequent maxillary sinusitis. New bone bridging the distraction gap was confirmed by radiography and histology in the animals completing distraction. Reconstruction of posterior maxillectomy defect is proven feasible by transport distraction osteogenesis.

Alveolar Process↗

[Distraction osteogenesis for treatment of temporomandibular joint ankylosis].

OBJECTIVE: To study the application of distraction osteogenesis in temporomandibular joint (TMJ) ankylosis patients. METHODS: 11 temporomandibular joint ankylosis patients (13 sides of TMJ) were treated by this technique. After removal of bony mass on the ankylosis area, a L-shape osteotomy of the ramus was performed to create the distraction transport disc which connected the mandible by distractor. Distractions were started on the 4 approximately 8th postoperative day. The distraction rhythm and rate were 0.25 mm 4 times a day. Distraction was stopped when contact was made between the transport disc and glenoid fossa. The patients underwent active mouth opening postoperatively. Distractor was kept in place for 3 approximately 4 months after completion of distraction and then removed under local anesthesia. RESULTS: Postoperatively, the range of mouth opening of the 11 patients (13 sides) was increased to normal (33 approximately 45 mm), bone formation in the gaps were perfect and the neocondyle was remodeling and approximated normal shape. No complications were found. CONCLUSION: Distraction osteogenesis for arthroplasty has many advantages compared with traditional methods. It is valuable in clinical practice as a new method for treatment of TMJ ankylosis.

Adolescent↗

[Sutural distraction osteogenesis for primary cleft palate repair: a preliminary clinical report].

OBJECTIVE: To probe the possibility of a new technique of primary cleft palate repair by sutural distraction osteogenesis. METHODS: The distractor was made of TiNi-shape memory alloy with 2 secure and 2 active arms. Under general anesthesia, 1 hole was drilled on each maxillary process and horizontal plate of palatine. The four arms of the distractor were inserted into holes. The palatine bones would then be distracted and moved medially and posteriorly. After 4 to 5 months' distraction, the two cleft edges approached gradually. The residual cleft, according to its width, was repaired by direct stitch of muco-periosteum incised at cleft edges, or with an additional relaxing incision on one side of the palate. Direct measurement of width of maxillary arch and the cleft, and the length of the hard palate was performed before and after distraction to evaluate the effects of distraction. RESULTS: Eight cleft children at their 2 to 4 years of age were treated by the new technique. Two of them terminated the procedure due to premature dislocation of the distractor. Six children underwent 37 to 126 days' distraction. Dramatic narrowing of the cleft and lengthening of hard palate were seen in these children, with the average narrowing of the cleft being 6.5 mm and average lengthening of the hard palate being 4.8 mm. CONCLUSION: It is clinically demonstrated that palatal tissue regeneration and cleft closure or narrowing and hard palate lengthening could be achieved by the technique of sutural distraction osteogenesis.

Child, Preschool↗

The role of hyaluronic acid, chitosan, and calcium sulfate and their combined effect on early bony consolidation in distraction osteogenesis of a canine model.

The purpose of this project was to study the effect of hyaluronic acid, calcium sulfate, and chitosan on early bony consolidation in distraction osteogenesis of a canine model. Sixteen dogs were used for this study. The lateral surface of the mandibular body was exposed in the subperiosteal plane, and the vertical osteotomy on the mandibular body was extended downward. An external distraction device was applied to the mandibular body, and the mandibular distraction was started 5 days after the operation at a rate of 1 mm/d up to a 10-mm distraction. The experimental group was then divided into a control group, chitosan group, hyaluronic acid group, calcium sulfate combined with hyaluronic acid group, and calcium sulfate combined with chitosan group, depending on the type of implantation material in the distracted area. After completing the distraction, implantation material was injected into the distracted area, although no material was implanted into the distracted area of the control group. After implanting the materials, the distraction device was left in place for 6 weeks to allow for bony consolidation. Four dogs were allocated to each group. Two dogs in each group (total of 8 dogs) were killed 3 weeks after implantation of the material, and the other 8 dogs were killed after 6 weeks. New bone was generated in the distracted zone of all groups. In the calcium sulfate combined with chitosan group and calcium sulfate combined with hyaluronic acid group, the formation of active woven bone was observed throughout the distracted zone. Moreover, the new bone seemed to be nearly normal cortical bone at 6 weeks after implantation. In the chitosan group and hyaluronic acid group, the development of new bone was observed in the distracted zone at 6 weeks. The amount was less than that in the calcium sulfate combined with hyaluronic acid group and calcium sulfate combined with chitosan group. These findings suggest that calcium sulfate and its combined materials seem to be quite effective in early bony consolidation in distraction osteogenesis.

Animals↗

Analysis of complications following alveolar distraction osteogenesis and implant placement in the partially edentulous mandible.

OBJECTIVE: The purpose of this retrospective study was to evaluate complications before, during, and after vertical alveolar distraction osteogenesis and to assess the survival rate of dental implants placed in distracted bone. STUDY DESIGN: In a consecutive series, 37 patients with 45 alveolar ridge deficiencies of the partially edentulous mandible were treated with 14 intraosseous and 31 subperiosteal distraction devices. Seventy-two dental implants could be placed at the time of distractor removal and 21 implants at a second stage. RESULTS: Complications associated with the distraction procedure affected 75.7% of patients. The majority of complications were of minor nature with the exception of fractures of basal bone (n = 3), fracture of transport segment (n = 1), breakage of distractor (n = 1), and severe mechanical problems (n = 3). Eleven secondary grafting procedures were necessary to allow the placement of dental implants. Implant survival was 95.7% (mean postloading follow-up: 35.7 months). CONCLUSION: Vertical alveolar distraction osteogenesis is not an uncomplicated procedure; however, long-term survival of dental implants inserted into distracted areas is satisfactory.

Adolescent↗

[Vertical distraction osteogenesis of the extremely resorbed edentulous mandible. A retrospective description of 16 patients].

This study's objective is to assess long-term results of vertical distraction osteogenesis for the extremely resorbed edentulous mandible by clinically measuring and taking x-rays from the beginning of the treatment of 16 subsequent patients to its final moment in the follow up period (ranging from 2-62 months). Bone height, nerve sensitivity, complications and loss of implant were registered. Average bone resorption after 3 years was 11.2%. Out of 16 patients 5 experienced sensory nerve disturbance; 3 suffered complications. The implant success rate was 89.2%. Distraction osteogenesis appears to be a reliable technique, with which stable bone tissue is developed. Risk of sensory nerve disturbance and complications however, must be taken into consideration.

Aged↗

Acceleration of callus maturation using rhOP-1 in mandibular distraction osteogenesis in a rat model.

The aim of this study was to assess if the application of rhOP-1 induces accelerated consolidation of the callus in mandibular distraction osteogenesis. In seven adult Wistar rats a bilateral osteotomy of the horizontal ramus of the mandible was performed in the molar region and a custom designed distractor was mounted to the mandible. With a rate of 0.7 mm per day the device was activated bilaterally after the seventh postoperative day. After seven days of distraction two times 50 microg rhOP-1 were injected on two subsequent days directly into the callus. The contralateral side received an injection of placebo solution. The animals were killed four weeks after the end of distraction. A three-point bending test revealed a significantly higher strength of the distracted mandible in the rhOP-1 side (66.3 N vs. 30.4 N, P=0.034, paired t-test). Undecalcified histological sections were examined using microradiography and fluorescence microscopy after sequential intravital polychromic labelling. A continuous bony bridging was seen in all rhOP-1 sites and in none of the control sites. The data indicate that rhOP-1 may be an option to accelerate callus maturation in mandibular distraction osteogenesis.

Animals↗

The overbite and intraoral mandibular distraction osteogenesis.

PURPOSE: The purpose of this study was to quantify the overbite reduction in skeletal Angle Class II malocclusions and discuss the management of the overbite during and after intraoral distraction of the mandible, and during orthodontic treatment with fixed appliances. MATERIAL AND METHODS: Cephalograms of 26 patients with an Angle Class II malocclusion and orthodontic appliances and distraction osteogenesis of the horizontal part of the mandible before (T0) and at least 1 year after treatment (T1) were evaluated. Mean age of the patients at the time of distraction was 14.6 years (range 12.8-15.9 years) and at the final registration 17.3 years (range 14.6-20.4 years). RESULTS: The overbite decreased significantly and the SpP/MP value increased significantly. The increase in the value of the Y-axis and the MP/SN angle before and after treatment was statistically insignificant. CONCLUSION: Opening of the bite during distraction of the mandible can be expected. The use of the 'floating bone' technique did not correct the overbite permanently. The patients in whom an open bite has already been treated are not ideal for mandibular lengthening by means of distraction osteogenesis.

Adolescent↗

Distraction osteogenesis in adolescents with maxillary arch deficiency and dental crowding: a 3-year follow-up.

BACKGROUND: In this study, the authors evaluated the long-term results after using anterior segmental osteotomy and distraction osteogenesis for the correction of sagittal maxillary deficiency associated with dental crowding. METHODS: Six young adolescents (four boys and two girls) underwent surgery and distraction at a mean age of 11.2 years (range, 10 to 12 years) and were followed up for 3 years. A tooth-borne distraction device was used for interdental distraction. The evaluation consisted of hard- and soft-tissue profile analysis and dental arch measurements before, immediately after, and 3 years after distraction. RESULTS: The results showed that the facial profile, the occlusion, and the dental crowding could be successfully corrected and that the results were stable after 3 years' follow-up. The mean facial convexity angle was changed from 1 to 8 degrees. The average advancement at point A was 4 mm and the SNA increased by an average of 4 degrees. Lengthening of the dental arch by an average of 4 mm created approximately 8 mm of new space, sufficient to resolve the dental crowding in all patients, thus avoiding an extraction of healthy teeth. CONCLUSION: The results of this study demonstrated that anterior segmental maxillary osteotomy combined with distraction osteogenesis offers an alternative for the treatment of adolescents suffering from sagittal maxillary deficiency with dental crowding.

Child↗

Osteofibrous dysplasia treated with distraction osteogenesis: a report of two cases.

We treated two patients with osteofibrous dysplasia of the tibia using en bloc marginal excision of the lesion and bone transport, a distraction osteogenesis procedure. In one patient, we had performed curettage procedures twice, each time followed by local recurrence and deformity. In contrast, with marginal excision and bone transport using an Ilizarov apparatus, the disease healed. In the other patient, we performed marginal excision and bone transport as the first procedure, which resulted in a healed lesion. In patients with osteofibrous dysplasia requiring treatment by an open method, curettage frequently is followed by local recurrence and deformity. We now prefer marginal excision of the lesion to avoid long-term failures, as in our first case. Distraction osteogenesis has proven useful for restoring structure and function in the affected limb.

Bone Neoplasms↗

Virtual 3D planning and guidance of mandibular distraction osteogenesis.

We present a system for 3D planning and pre-operative rehearsal of mandibular distraction osteogenesis procedures. Two primary architectural components are described: a planning system that allows geometric bone manipulation to rapidly explore various modifications and configurations, and a visuohaptic simulator that allows both general-purpose training and preoperative, patient-specific procedure rehearsal. We provide relevant clinical background, then describe the underlying simulation algorithms and their application to craniofacial procedures.

Computer Simulation↗

The use of distraction osteogenesis to induce new suprabony periodontal attachment in the beagle dog.

Using a technique called distraction osteogenesis (DO), orthopedic surgeons are capable of reconstructing 4 to 5 cm of bone and soft tissue without bone grafts or pedicle flap procedures. DO has been used recently to generate maxillofacial bone as an alternative to maxillary and mandibular osteotomies. Using DO methodology, this study attempted to regenerate supraalveolar buccal periodontium on the mandibular second, third, and fourth premolars of beagle dogs. A small but statistically significantly greater amount of new cementum was generated in experimental teeth, with no difference found between experimental and control groups with respect to regenerating alveolar bone. Further studies using modifications of this technique are warranted to explore the potential of DO as an alternative to conventional regenerative approaches.

Alveolar Bone Loss↗

[Distraction osteogenesis in the treatment of severe midfacial hypoplasia].

PATIENTS: Between May 1998 and May 2002, 38 patients suffering from severe midfacial retrusion and atrophy were treated by way of midfacial distraction osteogenesis. Diagnoses included cleft lip and palate (32 patients) and one case of Crouzon's disease. Ages ranged from 6-65 years. A total of 28 patients presented a velopharyngeal flap and nine patients were almost or fully edentulous. Using an extraoral halo device, distraction was performed after a subtotal Le Fort-I/II/III or modified quadrangular osteotomy. RESULTS: Distraction ranged from 9 to 31 mm (17 mm average). Following the primary operation, seven patients underwent a second intervention due to problems with the procedure or the device. Two patients needed a secondary Le Fort-I-osteotomy. With respect to velopharyngeal insufficiency, 21% showed a deterioration and 8% an improvement. Postoperatively, a decrease of 15-20% in the attained sagittal advancement was seen during the first 6 months. This was attributed to relapses and postoperative orthodontics. Thereafter skeletal stability was maintained. CONCLUSION: Distraction osteogenesis of the midface can be the method of choice in severe midfacial retrusion. Due to the difficult patient situation and the technical intricacies a higher complication rate has to be accepted than for conventional dysgnathia operations.

Adolescent↗

Distraction osteogenesis after membranous bone onlay grafting in a dog model.

PURPOSE: The purpose of this experiment was to study the possibility of distraction osteogenesis in a membranous bone onlay graft to the mandible and to clarify the histology of the bone repair. MATERIALS AND METHODS: Four dogs, 5 months of age at the beginning of the experiment, were used for this study. The zygomatic arch was exposed in the subperiosteal plane, and a 3-cm long, full-thickness portion of the arch was harvested. The lateral surface of the mandibular body was exposed in the subperiosteal plane, and the bone was fixed to the lateral surface as a membranous onlay graft using screws. A vertical osteotomy through the graft and underlying mandibular body was done postoperatively at week 1 in dog 1, week 2 in dog 2, week 3 in dog 3, and week 4 in dog 4. An external distraction device was applied to the mandibular body, and distraction was started 7 days after the operation at a rate of 1 mm/d for 10 days. After completion of distraction, the device was left in place for 6 weeks to allow for bony consolidation. Radiographs were carried out at 2, 4, and 6 weeks postdistraction. All dogs were killed 6 weeks after distraction. RESULTS: New bone between the native underlying mandibular segments was generated in the distraction zone in all dogs. New bone was not generated between the segments of the membranous bone onlay graft in dog 1, but was generated in dog 2, dog 3, and dog 4. However, in dogs 2 and 3, the new bone between the segments was less firm, with more fibrous tissue, than the bone between the native underlying mandibular segments. Histologically, the distraction gap between the segments of the membranous bone onlay graft in dogs 2 and 3 was composed of considerable fibrous tissue in the central zone and activated osteoblastic cells forming new bone in the margins. In dog 4, there was much more osteoblastic activity in the distraction gap, and the new bone had the appearance of almost normal cortical bone. CONCLUSION: These findings show that distraction osteogenesis is possible in a membranous bone onlay graft and suggest that the distraction should be performed at least 4 weeks after the onlay grafting.

Animals↗

The adaptation of soleus and edl in a rat model of distraction osteogenesis: IGF-1 and fibrosis.

The distraction rate of 0.5 mm/day produces good osteogenesis in small rodents; however, the effects of this distraction rate on muscle are not well documented. We evaluated the soleus and the extensor digitorum longus (EDL) after two weeks of lengthening distraction osteogenesis (DO) at 0.5 mm/day in skeletally mature rats. We found a modest but significant local increase of insulin like growth factor-1 (IGF-1) in the EDL, however, muscle growth indicated by developmental forms of myosin heavy chain (MHC) was not detected by mRNA (RT-PCR). To the contrary. the data suggested a decrease in cross-sectional area of the muscle fibers as well as a decrease in mRNA for slow MHC. Immunolabeling of fibronectin in cryosections of the EDL indicated fibrosis of the perimuscular connective tissue while assessment of the passive joint motion did not suggest a lack of excursion on the part of the dorsal flexors. While the literature suggests that IGF-1 facilitates muscle growth especially in young animals, excess of IGF-1 in muscle from adults may exacerbate DO-induced fibrosis.

Adaptation, Physiological↗