• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.4
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• pp.460-467
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• 2008

Pierre Robin sequence as a symptom triad of micrognathia, glossoptosis, and cleft palate results in upper airway obstruction and feeding problems. If mild, it is often managed in the prone position. When positional treatment fails, however, surgical intervention such as tongue-lip adhesion, tracheostomy, and mandibular distraction osteogenesis is mandatory to relieve airway obstruction. There has been growing interest in the application of distraction osteogenesis for the management of craniofacial abnormalities. The mandibular distraction osteogenesis to newborns may prevent the airway obstruction, decrease the potential tracheostomy, and reduce the likehood of orthognathic surgery after growth. We experienced an infant with Pierre Robin sequence who showed mandibular hypoplasia, glossoptosis, incomplete cleft palate, intermittent cyanos is, depression of the chest, and respiratory difficulty associated with airway obstruction. We treated the airway obstruction by tongue-lip adhesion at 2 weeks of age, and treated the mandibular retrognathism and depression of the chest byusing internal mandibular distraction osteogenesis at 7 month of age. The mandible moved forwardly, the upper airway space was enlarged, and the antero-posterior distance of the mandible was elongated after the mandibular distraction. Mandibular distraction osteogenesis may be a promising technique to avoid the need of tracheostomy and orthognathic surgery, and to correct airway obstruction in infants with congenital craniofacial malformation.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.3
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• pp.205-217
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• 2005

Distraction osteogenesis is a technique of lengthening bone including soft tissue by gradual separation of surgically divided bone surfaces. Although the biomechanical, histological, and ultrastructural changes associated with distraction osteogenesis have been widely described, the molecular mechanisms governing the formation of new bone in distracted bone segments remain largely unclear. However, such information has significant clinical implications because it may enable targeted therapeutic manipulations designed to accelerate osseous regeneration. The purpose of this study was to evaluate the expression of TGF-$\beta$1, IGF-I and bFGF in distraction osteogenesis according to different distraction rates in a rabbit's mandible. When twenty-four adult rabbits underwent open osteotomy between the premolar and mental foramen, an external bilateral distraction device was applied. Latency was allowed for five days before distraction. Three different distraction rates were 0.7 mm/day (A, n=8), 1.4 mm/day (B, n=8) and 2.4 mm/day (C, n=8). The distraction device was activated with the same distraction rhythms of twice a day until 4.9 mm (A & B group) and 8.4 mm (C group) length gains was achieved. The animals were sacrificed at postoperative 3, 7, 14 and 28 days. The bony specimens were stained with H&E for histologic examination, and RT-PCR analysis was done for the identification of the expression of TGF-$\beta$1, IGF-I and bFGF. The results obtained from this study were as follows : The 0.7 mm/day and 1.4 mm/day distraction rate groups were shown to improve regenerative bone formation on radiographic and histologic examination. Also, TGF-$\beta$1, IGF-I and bFGF expression increased in the 0.7 mm/day and 1.4 mm/day distraction rate groups. But the 2.4 mm/day distraction rate group specimen was different with adjacent normal bone and hardly expressed of growth factors. These findings suggest that improved new bone formation in the 0.7 mm/day and 1.4 mm/day distraction rates is associated with enhanced expression of TGF-$\beta$1, IGF-I and bFGF by mechanical tension stress. Additionally, the 0.7 mm/day and 1.4 mm/day distraction rate groups were significantly different from the 2.4 mm/day distraction rate group in the expression of growth factors. According to the above results, it seems possible to apply a distraction rate of up to 1.4 mm/day a day in rabbit's mandible. And further studies are needed to evaluate growth factors of TGF-$\beta$1 and IGF-I, which are excellent in expression.

• Archives of Plastic Surgery
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• v.35 no.3
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• pp.349-353
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• 2008

Purpose: There are 3 well-known surgical procedures to treat Pierre Robin sequence: tongue-lip adhesion, distraction osteogenesis of mandible, and tracheostomy. The classical tongue-lip adhesion is an effective way to keep airway. The tongue, however, becomes quite non-mobile and appears dormant until the patient could control upper airway and the adhesion can be maintained for prolonged period. Most of all, this procedure does not provide the correction of the micrognathia. Distraction osteogenesis is a good technique to correct micrognathia and to prevent tracheostomies in patients with Pierre Robin sequence. But airway keeping procedure is needed during the distraction period. The purpose of this study is to determine the usefulness of temporary tongue-lip traction during the initial period of mandibular distraction in Pierre Robin sequence patients with severe airway problems requiring operative procedure. Methods: It was a prospective study of 2 Pierre Robin sequence patients aged between 4 months and 6 months requiring surgical procedure to correct recurrent and severe pulmonary complications. Two patients underwent distraction osteogenesis of mandible. During the operation, deep one tension suture was performed to tract the tongue and lip. When the patient gained control of upper airway at the initial period of distraction and micrognathia was corrected, the traction suture was removed. Results: All patients were followed up. No patients complained severe pulmonary complications and tracheostomy could be avoided. No patients had severe pulmonary complication. The pulmonary condition of patients was good. Conclusion: In severe Pierre Robin sequence case, temporary tongue-lip traction is a good assistant method in distraction osteogenesis because this method can avoid tracheostomy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.3
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• pp.193-202
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• 2004

Distraction osteogenesis(DO) is defined as a gradual mechanical process of mechanical stretching two vascularized bone surface apart with a critical rate and rhythm such that new bone forms within the expanding gap, reliably bridges the gap, and ultimately remodels to normal structure. DO has become a mainstay in bone tissue engineering and has significantly improved our armamentarium for reconstructive craniomaxillofacial procedures. But the molecular and biological mechanisms that regulate the formation of new bone during distraction osteogenesis are not completely understood. BMPs are potent osteoinductive agents. Our hypothesis was that BMPs, especially BMP-2 and BMP-4, might play an importent role in the signaling pathways that link the mechanical forces created by distraction to biological responses and in promting new bone formation. Using a rabbit's mandible, we investigated the expression of BMP-2, -4 at different time points during distraction osteogenesis. The purpose of this study is to research the pattern of expression of BMP-2, -4 in new bone formation during distraction osteogenesis of the rabbit mandible. The experimental group was applied gradual distraction (0.7mm a day by twice a day, 4.9mm in total, for 7 days) and the control group was carried out osteotomy alone. They were examined clinically, histologically, and by RT-PCR analysis. On 3 days after osteotomy, the high level of expression of BMP-2, -4 was detected. But, the expression of BMP-4 was decreased during latency period. As distraction was started, its expression was increased and maintained till postoperative 28days. In control group, the expression of BMP-4was remarkably decreased till postoperative 14 days. On the other hand, the expression of BMP-2 was no difference between experimental group and control group. The expression of BMP-4 was maintanined at high level during the entire experimental period in both group. These findings suggested that excellent bone formation during distraction osteogenesis is associated with enhanced expression of BMP-4 genes by mechanical tension stress.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.5
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• pp.368-379
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• 2004

Distraction osteogenesis is a biologic process of new bone formation between the surfaces of bone segments that are gradually separated by incremental traction. Distraction osteogenesis is clinically applied as a new treatment modality of mandibular hypoplasia or bony defect area in maxillofacial area by many studies of distraction devices and method. But disadvantage of distraction osteogenesis shows unfavorably long consolidation period and relapse tendency. Therefore. this experiment was designed to investigate the effectiveness of combined application of distraction and compression force for improving of bone quality and shortening of treatment period during distraction osteogenesis. Twenty-one Sprague-Dawley rats with $300{\sim}350gm$ were used. These were divided into two group as distraction group and combination group was applied with compression force in the consolidation period. The rat were sacrificed for gross finding, radiographic and histologic findings. at 2, 4 weeks after distraction. The result were follow : 1. On radiographic finding, all experimental groups appeared more radiopacity than control groups both at 2, 4 weeks after distraction. 2. On histologic finding, trabeculae of bone and mature lamellar bone were showed increasingly in experimental group. Ossification occured rapidly. From this study, we may suggest that compression force application in consolidation period during distraction osteogenesis can be useful method improve bone quality and to shorten the treatment period. But more experimental and clinical studis are necessitated on effects of compression force application during distraction osteogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.5
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• pp.391-399
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• 2004

Distraction osteogenesis has been thought to be promising technique for replacing bone graft in maxilla and mandible. The purpose of this study was to investigate the expression of osteonectin on distraction osteogenesis. Sixteen rabbits were used for this experiment. Osteotomy was performed between premolar and mental foramen. On the experimental group, distraction device was connected to the respective bone segments. On the control group, bone segments were fixed using plate and screws after osteotomy. Distraction was carried out at the rate of 0.7mm per day to obtain a 4.9mm elongation on the experimental group. After 3 days, 7 days, 14 days, and 28 days two rabbits of each group were sacrificed. The results obtained from this study were as follow : Experimental group was observed that the gaps between the distracted bone edges were occupied by new bone. Expression of Osteonectin were detected throughout the experiment in both groups and Expression of Osteonectin were markedly increased during distraction and consolidation period in experimental group than control group. From these results, it could be stated that distraction was shown to improve and accelerate bone formation and mechanical stress like distraction has considerable effects on osteonectin.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.4
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• pp.317-326
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• 2006

Purpose : The aim of this study was to evaluate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) injected on the rate of new-bone formation for distraction osteogenesis on dogs. Materials & Methods : Twelve adult dogs were randomly selected into two groups of six dogs on each. Unilateral osteotomies were performed on the body of the mandible and an intraoral distractor was mounted to the mandible on dogs. One group was treated with injection of rhBMP-7 and the other group served as the control. RhBMP-7 was administered on the day of surgery by single injection into the medullary bone at the osteotomy gap. Distraction was performed five days after osteotomy as a rate of 0.5 mm twice per day for 10 days. The animals were then sacrificed at 2, 4, and 8 weeks after completion of the distraction. Two dogs in each group, totaling four dogs, were killed at 2 weeks, 4 weeks, and 8 weeks after completion of distraction, respectively. The lengthened mandibles were harvested and processed for radiographic and histological examinations. In addition, immunohistochemical examination using osteocalcin expression was studied. Results : Radiographs showed accelerated regenerate ossification with maturation of new bone in the rhBMP-7 group comparing with the control group at the 4 weeks of the consolidation. There was no significant difference in the radiographic findings at the 2 weeks and 8 weeks of the consolidation period. Histological findings demonstrated increased bone healing pattern in the rhBMP-7-treated group during all observation period. The expression of osteocalcin immunoreactivity was hardly detected in the normal mandible of dog, but the expression was detected in all experimental rhBMP-7 treated specimens. There were also significant increasing in number of positive immunostaining cells and staining intensity of osteocalcin expression in the rhBMP-7 treated group compared with those of the control group on 2-weeks and 4-weeks. There was a significant decreasing in staining intenstiy of all both two groups on 8 weeks of consolidation period, but significant differences of immunostaining was not seen in two groups. Conclusions : A single injection of rhBMP-7 at the time of osteotomy may stimulate the rate of regenerate ossification and increase callus maturation during distraction osteogenesis. In addition, it may shorten the distraction osteogenesis procedure and decrease the prevalence of complications associated with mandibular distraction osteogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.3
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• pp.250-265
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• 2008

Distraction osteogenesis is a well-established clinical treatment for limb length discrepancy and skeletal deformities. Appropriate mechanical tension-stress is believed not to break the callus but rather to stimulate osteogenesis. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. Although the biomechanical, histological, and ultrastructural changes associated with distraction osteogenesis have been widely described, the basic biology of the process is still not well known. Moreover, the molecular mechanisms in distraction osteogenesis remain largely unclear. Recent studies have implicated the growth factor cascade is likely to play an important role in distraction. And current reserch suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins. The purpose of this study is to examine the pattern of expression of growth factors($TGF-{\beta}1$, IGF-I, bFGF) and extracellular matrix proteins(osteoclacin, osteonectin) related to osteogenesis by osteodistraction of the mandible in rabbits. 24 rabbits is used for this experiment. Experimental group are gradual distraction(0.7mm, twice/day), acute distraction(1.4mm, twice/day) and control group is only osteotomized. After 5 days latency, osteotomic site is distracted for each 7 days and 3.5 days. Consolidation period is 28 days. The animal is sacrificed at the 3th, 7th, 14th, 28th. The distracted bone is examined by immunohistochemical analysis and RT-PCR analysis. The results obtained from this study were as follow : No significant difference was found on clinical examination according to distraction rate, but gradual distraction was shown to improve regenerate bone formation on radiographic and histologic examination. Growth factors and extracelluar matrix proteins expression increased in distraction group than control group. From these results, it could be stated that graudal distraction is shown to improve and accelerate bone formation and mechanical stress like distraction has considerable effects on osteogenesis related factors. And rabbit is the most appropriate animal model for further reseach on the molecular mechanisms that mediate osteodistraction. It is believed that understanding the biomolecular mechanisms that mediate distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone healing.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.4
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• pp.315-323
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• 2005

For reconstruction of the bony defect, distraction osteogenesis has many advantages in comparison with bone graft. However, it needs long consolidation period for sufficient bone maturity. This study is performed to evaluate the effect of PRP injection into the distracted mandible on bone formation in rabbits. Twelve house rabbits, weighing 2 kg, were used. All animals underwent bilateral mandibular osteotomy under general anesthesia. A internal distractor divice was positioned along a plane perpendicular to the line of osteotomy. After 5 days of latency period, distraction osteogenesis was started at a rate of 1 mm/day for 9 days which was distracted 9 mm totally. After completion of distraction, 0.5 ml of PRP which collected in rabbit blood was injected into the distracted mandible on experimental group, whereas no injection was done in control group. Macroscopical, radiographical, and histological, and histomorphometric examinations were performed 2, 4 and 8 weeks after distraction. All animals showed distracted mandible and severe anterior cross-bite. In radiographical findings 2 weeks after distraction, more radiopacity in the distracted gap was found in experimental group than that of control group. At 4 weeks after distraction, distracted bone was similar to normal bone in experimental group. In histological findings, 1) At 2 weeks after distraction, number of osteoblasts and angiogenesis in the distracted gap was found in experimental group than that of control group. 2) At 4 weeks after distraction, more active and distinct bone in the distracted gap was found in experimental group than that of control groups. 3) At 8 weeks after distraction, more dense and matured lamellated bone in the distracted gap was found in experimental group than that of control group. In histomorphometrical findings 8 weeks after distraction, more bone formation was observed in experimental group than control group (p<0.01). These results indicate that administration of PRP into the distracted mandible can promote bone formation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.3
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• pp.241-249
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• 2006

Purpose For the reconstruction of craniofacial deformities, the distraction osteogenesis is an useful method which can make new soft tissues as well as new bone. Although the distraction osteogenesis is an effective procedure in quantitative aspects, the new bone formed by this procedure can be coarse in qualitive aspects sometimes. Materials and methods Twelve rabbits, weighing about 2 kg, were included and the prefabricated distraction device were used. After a latency period of 5 days, in the experimental group (n=6), the mandible was distracted at the rate of 1.0 mm/day for 2 days and then compressed with 1.0 mm for the next 3rd day, therefore distracted totally to a length of 1.0 mm for 3 days. This procedure was repeated 5 times and, as a result, the experimental group was distracted to a length of 5.0 mm for 15 days finally. In the control group (n=6), the mandible was distracted totally to a length of 5.0 mm at the rate of 1 mm/day. At 2 weeks and 8 weeks of consolidation in the control group, 3 rabbits in each group were sacrificed and their biopsy specimens from the distracted mandible were taken. Results All animals showed the mandibular elongation clinically and radiographically. Histologically, many blood vessels, osteoblasts and immature bones formed by osteoid deposition were observed in the experimental group at 2 weeks. At 8 weeks, the bony trabeculae were thicker than the ones in the control group and were composed of lamella bones and woven bones in the experimental group. On histomorphometric analysis, the bone deposition area of the distracted site was broader in the experimental group $(273.8{\pm}115.7\;cm^2)$ than the one in the control group $(199.4{\pm}101.4\;cm^2)$. Futhermore, the modified rate of bone deposition area was higher in the experimental group (48${\pm}$20%) than the one in the control group (35${\pm}$18%). However, these data showed no significant differences statistically. Conclusion These results suggest that the distraction osteogenesis by using an alternating distraction/compression protocols is an effective method for increasing new bone formation in distracted areas.