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[Tissue regeneration by distraction osteogenesis].

"Distraction Osteogenesis" after osteotomy (or corticotomy) is also called "Distraction Histogenesis" because it could increase not only bone mass but also surrounding soft tissue.Moreover, jaw bone reconstruction using this technique after cancer surgery has successfully established without artificial materials nor bone transplantation.

English Abstract↗

Changes in the inferior alveolar nerve following mandibular lengthening in the dog using distraction osteogenesis.

Distraction osteogenesis as per Ilizarov was used to lengthen the canine mandible. In this study, physiological and ultrastructural examination of the inferior nerve was performed. Mandibular body corticotomies were performed, and the mandible was distracted 7 mm. The animals were killed 4 weeks after the distraction was completed. Bone formed within the distraction gap in all dogs. There was no statistically significant difference in the jaw-jerk voltage between control and experimental sides. There was a significant difference between the distracted and control nerves in only one area of one nerve.

Animals↗

Preliminary studies of mineralization during distraction osteogenesis.

Distraction osteogenesis by the Ilizarov method was performed on 20 dogs. Mineralization at the site of the left tibial metaphyseal lengthening was measured by weekly quantitative computer tomography (QCT) using the contralateral tibia as a control. Four dogs each were killed on Days 7, 14, 21, and 28 of distraction in order to correlate QCT with microradiology, nondecalcified histology, quantitative calcium analysis, and scanning electron microscopy. It was consistently found that intramembranous ossification proceeded centripetally from each corticotomy surface toward the central fibrous interzone. Bone columns crystallized along longitudinally oriented collagen bundles, expanding circumferentially to surrounding bundles. As the distraction gap increased, the bone columns increased in length and in diameter, while the fibrous interzone remained about 4 mm long. Histologically, the bone columns resembled stalagmites and stalactites, as seen by microradiography and scanning electron microscopy, that projected from each corticotomy surface toward the center. These cones reached maximum diameters of 150-200 mu at the corticotomy surfaces. Radiodensity (QCT) increased gradually from the central fibrous interzone toward each corticotomy surface. Mineral density, as determined by calcium quantification, reflected the microscopic geometry and radiographic polarity.

Animals↗

Sutural distraction osteogenesis (SDO) versus osteotomy distraction osteogenesis (ODO) for midfacial advancement: a new technique and primary clinical report.

A new technique of osteotomy distraction osteogenesis (ODO) and sutural distraction osteogenesis (SDO) by the use of bone-borne traction hooks is presented. The technique of osteotomy plus distraction osteogenesis is suitable for adult patients. The technique of sutural distraction osteogenesis is suitable for young patients, ages 6 through 12 years. The distraction system consists of a face-bow, orthodontic elastics, and bone-borne traction hooks. The bone-borne traction hooks are made of titanium, with two traction hooks running laterally or downwardly. When a Le Fort III osteotomy is needed, bone-borne traction hooks are inserted through the nostrils into a bone hole drilled at the lateral-inferior pyriform aperture. When no osteotomy is needed, only the bone-borne traction hooks are placed. Heavy elastics were used in the technique of osteotomy distraction osteogenesis for Le Fort III osteotomy adult patients, whereas light forces and thus light elastics were used for younger patients. Three adult patients and four children were treated by osteotomy distraction and sutural distraction, respectively. All seven patients with midfacial hypoplasia established a harmonious facial profile and normal occlusal relationships. Radiographic examination showed balanced advancement of the midfacial skeleton. It is suggested that the treatment of midfacial hypoplasia in children by the technique of sutural distraction osteogenesis is to be preferred because of its simplicity and relative noninvasiveness. Thus, the authors suggest that midfacial hypoplasia should be treated at a younger age by this technique, potentially eliminating the need for a Le Fort III osteotomy at an older age.

Adolescent↗

Amniotic band sequence: the use of bone grafting and distraction osteogenesis.

Distraction has proven to be a useful technique in cases of severe bone deficiency in the craniofacial skeleton. This is a report of its use in the treatment of a child affected by amniotic band sequence. This 5 year old Hispanic female presented with transverse deficiences of one lower extremity and both upper extremities. Additionally, she was missing the mandible and overlying soft tissue from ramus to ramus. Although free fibula transfer was a possibility, due to the presence of only one lower extremity, it was elected to utilize the technique of distraction. After preliminary bone grafting to unite these two hemimanibles, the bone graft was distracted bilaterally to create a neomandible. Following consolidation and removal of the distraction devices, the child was markedly improved despite what appeared to be a pathologic fracture in the region of the mandibular angle. Repeat distraction was planned.

Amniotic Band Syndrome↗

Reconstruction of mandibular defects following tumor ablation by vertical distraction osteogenesis using intraosseous distraction devices.

OBJECTIVES: Distraction osteogenesis has recently evolved a challenging technique to overcome major drawbacks of conventional augmentation procedures. We, therefore, report the application of miniaturized intraosseous distraction devices for the rehabilitation of mandibular defects due to ablative tumor surgery. METHODS: In 10 patients who had undergone box-shaped or segmental resections, augmentation of the residual mandibular bone or of full thickness iliac crest grafts was performed by intraosseous implant-shaped distractors. Distraction and reconsolidation was monitored by ultrasonography. Implants were inserted within 1 week after active distraction. Median follow-up after implant insertion was 38 months. RESULTS: On average, a vertical gain of 7.3 mm was obtained by distraction. Except for one case (local infection), all distraction zones showed complete ossification by radiologic and ultrasonographic evaluation. Overall 28 implants were placed in the distracted bone. Two implants were lost at 2.4 and 22 months after placement. The estimated 4-year implant survival rate in this population was 90%. For the endpoint 'bone loss' (>1.5 mm in the first and >1 mm in following years), the estimated 4-year success rate was 59% with four out of seven events occurring in a single patient (patient No. 1 of this series). CONCLUSION: Vertical distraction by means of implant distractors could be performed with reasonable success in tumor patients with box-shaped resection defects or undercontoured bone grafts. Overall morbidity was very low. Even though blood supply is continuously maintained in distraction osteogenesis, bone resorption remains a critical issue for this reconstruction technique too.

Adult↗

The effect of low-intensity pulsed ultrasound on callus maturation in tibial distraction osteogenesis.

Callus distraction is currently the most popular method of bone lengthening. Prolonged treatment time is one of its major problems. In this study, we investigated the effect of low-intensity pulsed ultrasound on tibial distraction osteogenesis. We managed 20 patients with tibial defects ranging from 5 cm to 8 cm with distraction osteogenesis using the Ilizarov external fixator. After the completion of distraction, ten patients received daily 20 min of low-intensity pulsed ultrasound stimulation (30 mW/cm2) onto the bone lengthening site (group A) while rigid fixation was maintained in the remaining patients (group B). All patients were followed with weekly radiographs to determine the formation of an external cortex and an intramedullary canal, at which time the fixator was removed. The mean healing index in group A was 30 (27-36) days/cm while it was 48 (42-75) days/cm in group B. In group B, one patient failed to consolidate the regenerated bone. Low-intensity pulsed ultrasound stimulation is highly effective in achieving maturation of bone and reducing time of distraction osteogenesis.

Adolescent↗

Tensile mechanical strain up-regulates Runx2 and osteogenic factor expression in human periosteal cells: implications for distraction osteogenesis.

PURPOSE: Distraction osteogenesis is now accepted as a standard treatment in oral and maxillofacial reconstructive surgery. In the process of bone regeneration with the application of strain, the periosteum might be very involved in osteogenesis. This study examined the effect of mechanical strain on periosteal cells and the implications for distraction osteogenesis. MATERIALS AND METHODS: Periosteal cells were obtained from mandibular periosteum that was excised while extracting impacted wisdom teeth. Mechanical strain was applied using a specially designed apparatus with flexible silicon bottom chambers. The levels of mRNA of the osteoblast differentiation factor Runx2 (Cbfa1/AML3/Peb alpha A) and osteogenic factors were analyzed at different times using the reverse transcription-polymerase chain reaction method to evaluate the effect of the strain. RESULTS: The periosteal cells expressed the osteogenic phenotype. The strain had a shaping effect on the cells. The application of tensile strain strongly activated the expression of osteogenic and angiogenic growth factors, and up-regulated the expression of Runx2, an osteoblast-specific transcription factor. CONCLUSION: Tensile strain may initiate the differentiation of periosteal cells into osteogenic cells, inducing the expression of Runx2 in the process of bone regeneration. Therefore, the periosteum is profoundly involved in bone formation and regeneration, especially in distraction osteogenesis.

Bone Regeneration↗

Hybrid of distraction osteogenesis unilateral frontal distraction and supraorbital reshaping in correction of unilateral coronal synostosis.

Unicoronal synostotic plagiocephaly is routinely treated by intracranial wide frontal and bilateral supraorbital reshaping. Recent advancement of distraction osteogenesis in craniofacial surgery has extended to patients with craniosynostosis. Although a controversy remains between conventional osteotomy and reshaping and application of the distraction technique in surgical treatment of craniosynostosis, there have been several positive clinical reports on distraction techniques for nonsyndromic and syndromic craniosynostosis. Unicoronal distraction applied successfully to a case of frontal plagiocephaly has been described. The authors report a procedure: hybrid of unilateral frontal distraction and supraorbital reshaping on the affected side for frontal synostotic plagiocephaly. This procedure was conducted on four typical unicoronal synostotic plagiocephaly cases (patient age range, 9-14 months; all patients female) with successful results. No particular complications were encountered in any of the four cases with a follow-up period that ranged from 18 to 53 months.

Craniosynostoses↗

Does the sheep mandible relapse following lengthening by distraction osteogenesis?

AIM: Distraction osteogenesis is a technique used to lengthen the shortened mandible. However, the long term stability of the distracted mandibular bone is not known. The aim of this study was to assess if the sheep mandible relapses following lengthening, and to assess the quality of distracted bone up to 1 year post lengthening. METHODS: Twenty-four sheep had bilateral external mandibular distractors applied, with three sheep as controls. Titanium marker screws were positioned both proximal and distal to the distraction zone in all sheep. Following a 5 day latency period, the interdental gap was distracted 1 mm/day for 20 days, with a subsequent 20 day consolidation period. Ante-mortem serial X-rays were used to assess for relapse by measuring the distance between the screws. The animals were sacrificed at either 3, 6, 9 or 12 months post-distraction. At post mortem, the distance between the screws was re-measured. The distracted bone was assessed mechanically and histologically. RESULTS: The mean mandibular lengthening obtained was 13.2 mm. There was no relapse of the mandible over 12 months. The distracted bone had attained the strength and stiffness of undistracted bone by 6 months post-distraction (p < 0.05). Histological evaluation revealed significant amounts of lamellar bone by 6 months post-distraction. CONCLUSIONS: No relapse occurred for 12 months post distraction lengthening. The bone formed following distraction was stable and of good quality. These findings lend support to the use of distraction osteogenesis in clinical practice.

Analysis of Variance↗

Temporospatial expression of vascular endothelial growth factor and basic fibroblast growth factor during mandibular distraction osteogenesis.

OBJECTIVE: Distraction osteogenesis is a vascular-dependent process. This study investigated expression patterns of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), in the distracted calluses following mandibular lengthening in a goat model. MATERIAL AND METHODS: Bilateral mandibular osteotomies were performed in 15 young adult goats. After a latency of 7 days, the mandibles were elongated using custom-made distractors with a rate of 1 mm/day for 10 days. Three animals each were sacrificed at the end of the delay phase, at 0, 7, 14, and 28 days after completion of distraction, respectively. The lengthened mandibles were harvested and processed for histological and immunohistochemical examinations. RESULTS: Elevated cellular expression of VEGF and bFGF, with neovascularization in the distraction gap, was observed following mandibular lengthening. VEGF staining was noted in the endothelial cells and osteoblasts. bFGF staining was seen in the fibroblast-like cells, osteoblasts and immature osteocytes. Their strongest expression was found 0-7 days after the end of distraction, and declined with maturation of the newly formed bone. CONCLUSION: A temporal and spatial expression pattern of VEGF and bFGF was found during distraction osteogenesis in goat mandibles. It suggests that distraction forces can stimulate the production of VEGF and bFGF, which contribute to neovascularization and new bone formation during gradual distraction of the mandible. Application of angiogenic factors may be considered as a potential method to enhance angiogenesis and osteogenesis in osteodistraction, especially in sites without enough vascularization.

Animals↗

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.

Adult↗

Distraction osteogenesis to achieve mandibular vertical bone regeneration: a case report.

In this case report a surgical technique for vertical ridge augmentation is presented. The procedure, performed in a 30-year-old woman with an atrophied alveolar ridge in the anterior portion of the mandible, is based on the biologic concept of osteogenesis distraction previously introduced in orthopedic and maxillofacial surgery. After elevation of a full-thickness flap a horizontal osteotomy was performed 7 to 8 mm from the top of the ridge. Two vertical osteotomies were prepared with drills of increasing diameter (2, 2.8, and 3.25 mm), tapping was performed for the first 5 to 6 mm, and two distractor base plugs were placed at the base of the osteotomies with a repositioning tool. An intraosseous distraction implant was then inserted and 2 inward vertical cuts were made in the bone to allow proper distraction to take place. Correct functioning of the device was checked by distracting the bone fragment 1 mm using the axial distraction screw. A latency distraction healing screw was inserted in each of the distraction implants and the area was left to heal for 5 days. Once primary healing had occurred, the distraction of the newly formed bone callus was activated each day for 10 days (1 mm per day). At the end of the distraction period a final distraction screw was left in place and a final healing screw was inserted. During this time there were no complications and the patient on no occasion complained of discomfort. The distractor device was removed 30 days later, leaving the base plugs in place. One month later a vertical augmentation of 7 mm had been achieved; the base plugs were removed, 3 intraosseous implants were inserted, and a biopsy of the newly formed tissue was obtained. Histologic evaluation of the biopsy specimen showed woven bone formation approximately 75 days after the initial procedure.

Adult↗

Transmaxillary osteogenesis distraction combined with orthopedics and orthodontics in the correction of a severe retrusion of the upper maxilla.

A patient having adequate records and diagnosed as having Binder syndrome is presented. Nasomaxillary hypoplasia requires a definitive treatment, use of bone grafts, upper maxillary osteotomies, and advancement or a combination of both. Bone grafts can be reabsorbed, and complete maxillary advance modifies normal occlusion in a certain way, because the posterior sector is not compromised. The aim of this case treatment is to create a new osseous surface that makes the eruption of the permanent dental pieces easier and gives the correct skeletal position to the upper maxilla with distraction osteogenesis combined with an orthopedic appliance, transmaxillary segment osteotomy, and subsequent orthodontics. The absence of the osseous surface in the upper maxilla and the presence of supernumeraries in the anterior region determined the permanence of most of the temporary dental pieces, resulting in the impossibility of making the exchange to permanent dental pieces. The technique and the devices are simple and easy to manipulate. After the treatment, an adequate dental relation is restored as well as effective advance of the upper maxillary bone; thus, an excellent functional and stable esthetic result is achieved, avoiding any complication of velopharingeal incompetence.

Child, Preschool↗

Osteoclastogenic activity during mandibular distraction osteogenesis.

Mandibular distraction osteogenesis is a well-developed clinical modality for the treatment of craniofacial deformities and dental arch discrepancies, in combination with orthodontic treatment. However, in our previous study, orthodontic tooth movement into the distraction gap caused severe root resorption. The present study aimed to clarify the osteoclastogenic activity of cells in the distraction gap. We hypothesized that the gene expression of osteoclastogenic- and osteoclast-supporting molecules in osteoblasts and stromal cells would increase at distraction sites during the consolidation period. An animal model experiment involving rabbits was designed for mandibular distraction osteogenesis and subjected to in situ hybridization analysis. The number of osteoclasts was larger in the distraction gap during the early consolidation period than in normal controls, due to an increase of gene expression for osteoclastogenic cytokines in osteoblasts. It was concluded that osteoclastogenic and osteoclastic activities are stimulated at distraction sites during the early consolidation period.

Animals↗

Effects of latency period in a rabbit mandibular distraction osteogenesis.

Recently, distraction osteogenesis has been widely used in the craniomaxillofacial skeleton. There are varying views, however, about the need for a latency period for mandibular distraction, which has been reported from 0 to 14 days. We used a rabbit model to determine the ideal latency period for mandibular distraction osteogenesis. We performed a subperiosteal corticotomy of the bilateral mandible and then applied an external device. We used 0-, 2-, 5-, and 10-day latency periods. Distraction was done at a rate of 0.5 mm per day (0.25 mm every 12 h) to elongate by 5 mm after each latency period. Hematoxylin-eosin stain was used for histologic observation, and bone labelling was observed with a fluorescence microscope. In the 0-day latency, the lengthened region was filled with fibrous tissue. Cartilage formed like isles along the lengthened edge. In the 10-day latency, the lengthened region was almost completely filled with woven bone. In the 2- and 5-day latency, there were mineralization zones at the periphery of this fibrous interzone. The primary osteon remodelling zones were located at both ends of the zones of mineralization zones. In the 5-day latency, new bone formation was observed around the periosteum.

Animals↗

Rat mandibular distraction osteogenesis: part III. Gradual distraction versus acute lengthening.

Distraction osteogenesis is a well-established method of endogenous tissue engineering. This technique has significantly augmented our armamentarium of reconstructive craniofacial procedures. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been extensively described, the molecular mechanisms governing successful membranous distraction remain unknown. Using an established rat model, the molecular differences between successful (i.e., osseous union with gradual distraction) and ineffective (i.e., fibrous union with acute lengthening) membranous bone lengthening was analyzed. Herein, the first insight into the molecular mechanisms of successful membranous bone distraction is provided. In addition, these data provide the foundation for future targeted therapeutic manipulations designed to improve osseous regeneration. Vertical mandibular osteotomies were created in 52 adult male Sprague-Dawley rats, and the animals were fitted with customized distraction devices. Twenty-six animals underwent immediate acute lengthening (3 mm; a length previously shown to result in fibrous union) and 26 animals were gradually distracted (after a 3-day latency period, animals were distracted 0.25 mm twice daily for 6 days; total = 3 mm). Four mandibular regenerates were harvested from each group for RNA analysis on 5, 7, 9, 23, and 37 days postoperatively (n = 40). Two mandibular regenerates were also harvested from each group and prepared for immunohistochemistry on postoperative days 5, 7, and 37 (n = 12). In addition to the 52 experimental animals, 4 control rats underwent sham operations (skin incision only) and mandibular RNA was immediately collected. Control and experimental specimens were analyzed for collagen I, osteocalcin, tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor mRNA and protein expression. In this study, marked elevation of critical extracellular matrix molecules (osteocalcin and collagen I) during the consolidation phase of gradual distraction compared with acute lengthening is demonstrated. In addition, the expression of an inhibitor of extracellular matrix turnover, tissue inhibitor of metalloproteinase-1, remained strikingly elevated in gradually distracted animals. Finally, this study demonstrated that neither gradual distraction nor acute lengthening appreciably alters vascular endothelial growth factor expression. These results suggest that gradual distraction osteogenesis promotes successful osseous bone repair by regulating the expression of bone-specific extracellular matrix molecules. In contrast, decreased production or increased turnover of bone scaffolding proteins (i.e., collagen) or regulators of mineralization (i.e., osteocalcin) may lead to fibrous union during acute lengthening.

Animals↗

Applications of distraction osteogenesis. Part I.

Distraction osteogenesis (DO) of facial bones is a recent development in the treatment of pediatric patients. The use of DO in current clinical practice of pediatric reconstructive surgery is primarily limited to severe deformities of the lower jaw, most of which are congenital in nature. Clinical experience with DO for early facial deformities remains limited, and no authoritative works are currently available to guide clinicians in the techniques or indications for DO of the facial skeleton.

Child↗