Distraction osteogenesis in maxillary deficiency using a rigid external distraction device.
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Biomedical subjects
Publications and source records attributed to Adi Rachmiel.
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PURPOSE: Bone regeneration is crucial in the healing of defects in the craniofacial complex. The ability of transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1), incorporated into a hydrogel scaffold to induce bone regeneration, was evaluated in a rat mandible defect model. MATERIAL AND METHODS: Hydrogel scaffolds containing either transforming growth factor-beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1), TGF-beta+ IGF-1, or saline, were implanted in rat mandibular bone defects. In a control group the defects were treated by saline alone. Bone defect healing was tested after 3 and 6 weeks by radiology and morphology. RESULTS: Soft tissue radiographs indicated that the area of new bone formation increased gradually after 3 and at 6 weeks. The percentage of closure after 3 weeks was less than the percentage closure after 6 weeks. The amount of calcified material in the TGF-beta and TGF-beta+IGF-1-treated groups had increased more than in the saline-containing hydrogel and control (saline-treated) defects. The percentages of defect closures were 37, 38, 24, 14, and 11% after 3 weeks, and 94, 91, 84, 72, and 29% after 6 weeks, in the TGF-beta+IGF-1, TGF-beta, IGF-1, saline containing hydrogel and saline-treated animals, respectively. Three-dimensional computerized tomography (3D CT) images showed that the 3D shape of the bones was restored. Morphological analysis of the defects treated with hydrogel containing TGF-beta, IGF-1 or TGF-beta+IGF-1 revealed significant bone formation after 6 weeks. CONCLUSION: It is concluded that the hydrogel scaffold impregnated with growth factors can induce bone regeneration and is therefore a promising surgical tool for enhancement of surgical repair of bone defects.
Distraction osteogenesis for correction of horizontal alveolar width deficiency was performed for 9 patients by using an alveolar crest widening device. Four prototypes were used during the course of the study until a final protocol was achieved. Under local anesthesia, a blind crestal osteotomy was carried out with minimal periosteal reflection. The horizontal distraction device was placed percutaneously. Distraction proceeded from the seventh postoperative day at a rate of 0.4 mm/day for 14 to 18 days. Seven to 10 days later, dental implants were placed. Distraction osteogenesis occurred in all 9 patients and increased alveolar width from 4 to 6 mm. Twenty implants successfully osteointegrated of 21 placed. Marginal bone resorption was not observed after 12 months' follow-up. The advantages of horizontal distraction over block grafting include simultaneous expansion of soft tissue, high degree of dimensional stability, abbreviated overall treatment time, and no graft requirement.
BACKGROUND: The purpose of this study was to perform alveolar ridge augmentation by distraction osteogenesis (DO) and to enhance bone regeneration through the use of recombinant human bone morphogenetic protein-2 (rhBMP-2), followed by implant placement. METHODS: Alveolar segmental osteotomy was performed in the mandible of 10 sheep followed by placement of 1.5 mm alveolar distraction devices. The study group was injected on the fifth day of distraction with a single dose of 10 microg rhBMP-2. Only distraction was performed in the control group. RESULTS: A mean alveolar augmentation of 12 mm was achieved. After 12 weeks of consolidation, the distraction devices were removed and biopsies were taken for histological and immunohistochemical characterization and morphometry of the newly formed bone. Titanium threaded cylindrical implants were then placed in the newly augmented bone. Radiological evaluation showed lifting of the transport segment and integration of the implants within both the transport segment and the regenerated bone. The histological study demonstrated that the association of DO and BMP resulted in increased trabecular bone size and volume (32.2%+/-0.95% versus 18.6%+/-0.71%; P <1 x 10(-17) after 24 days of lengthening and 63.8%+/-1.89% versus 42.5%+/-1.33%; P<1 x 10(-15) after 12 weeks of consolidation) and increased numbers of proliferating cell nuclear antigen stained cells (0.7+/-0.04 versus 0.47+/-0.04; P<1 x 10(-10)) compared with the DO only group. CONCLUSIONS: Alveolar distraction augments atrophic alveolar ridge and creates new bone that permits implant placement. rhBMP-2 enhances bone quality and may shorten the consolidation period of distraction allowing for earlier implant placement.
Bone cells respond to mechanical stimulation by gene expression. The molecular events involved in the translation of mechanical stimulation into cell proliferation and bone formation are not yet well understood. We looked for the expression of early-response genes of the AP-1 transcription factor complex in an in vivo bone regeneration system subjected to mechanical forces because these genes were found to be related to mechanotransduction and important for bone development. Sheep maxillary bone was distracted daily for 15 days. c-Jun and c-Fos were evaluated by Northern blotting analysis and immunohistochemistry in biopsy specimens removed at 8 and 15 days and were compared with post-osteotomy but not distracted repair tissue. Elevated levels of c-Jun and c-Fos mRNA were found after 8 days of distraction. Likewise, mesenchyme-like and fibroblast-like cells composing the 8-day distracted regeneration tissue showed increases in the intensity of immunostaining compared to cells in the corresponding non-distracted fracture repair tissue. After 15 days of distraction, when bone trabeculae start to form distally and proximally in the distracted regeneration tissue, mostly preosteoblasts and osteoblasts retained c-Fos and c-Jun immunoreactivity, similar to bone-associated cells in control non-distracted fracture repair tissue. We propose that the elevated expression of c-Jun and c-Fos is related to mechanical stimulation in this in vivo bone regeneration system.
Distraction osteogenesis is becoming the treatment of choice for the surgical correction of hypoplasias of the maxillofacial skeleton. The mandible can be elongated by intraoral or extraoral devices. The intraoral devices are smaller, do not leave an external scar and do not cause social inconvenience to the patient. The main disadvantages are less control of vector and the need for a second operation for removal. The most important factors of mandibular distraction are planning of distraction, location of the osteotomy, control of vector of lengthening and type of distraction device. In the maxilla, our experience with three types of maxillary distraction is discussed: 1) the rigid extraoral distraction, 2) the surgically assisted protraction and 3) the intraoral method. In the last years, distraction osteogenesis was applied in the treatment of obstructive sleep apnea. The method has several advantages over other methods, mainly in treatment of young children in order to improve airway and to decannulate tracheostomy. Alveolar distraction osteogenesis poses a new challenge in reconstructing atrophic alveolar bone with no need to harvest bone graft or to use bone substitutes. The advantages and problematic issues of alveolar distraction such as vector control of distraction are described. The intraoral method should always be considered first. However, in severely hypoplastic patients, when three-dimensional correction is necessary, the extraoral device has an advantage over the intraoral device. In the future, the issues to consider will be improvement of osteotomies by endoscopy, development of smaller multidirectional devices, improvement of bone quality by cytokines and growth factors in order to shorten the time of device bearing by the patients.
The purpose of the study was to follow the early events in bone formation and neovascularization during maxillary distraction and after the consolidation period and to define the characterization of the new bone in the distracted area. Maxillary osteotomy was performed in seven sheep. In five animals, an external distraction device was used for maxillary lengthening of 20 mm at a rate of 1 mm/day for 20 days. Another two animals served as controls without distraction. Sequential biopsies were performed. The methods used for analysis were histologic, immunohistochemical, and ultrastructural by transmission electron microscopy. During the 5 days of latency, a fibrin clot was formed that after 5 days of distraction was replaced by granulation tissue, proliferating mesenchyme-like cells, and capillaries. After 10 days of distraction, the regenerated tissue could be divided into three main zones and two transitional areas: a central zone occupied by many polygonal mesenchyme-like cells and spindle-shaped cells that proliferated intensively; two paracentral zones on both sides of the central zone in which many cells showed morphologic signs of apoptosis leading to a decreased number of fibroblast-like cells embedded in wavy collagen fibers; a transitional area from the central to the paracentral zone in which concentric cellular colonies were believed to represent a novel form of vasculogenesis; distal-proximal zones, located on both sides of the paracentral zones and in continuation with the old bone, showed delicate new woven bone trabeculae that grew continuously in the direction of lengthening and gradually became mineralized; and a transitional area from the paracentral to the distal-proximal zones in which there was recruitment of preosteoblasts from the distracted tissue to the trabecular tips. These further differentiated into osteoblasts that contributed to the trabecular growth. The histologic feature pattern was similar after 15 and 20 days of continuous distraction. At the end of lengthening, after 20 days, delicate longitudinally oriented trabeculae continued to grow by recruiting preosteogenic cells from the central distracted tissue, became mineralized, and were rimmed by osteoblasts. After 6 weeks of retention, the trabeculae thickened and consisted of a mixture of lamellar and woven bone. In conclusion, the distraction force creates a pool of undifferentiated mesenchyme-like cells with osteogenic potential and triggers capillary formation, a clear zonation can be observed during active lengthening, and new bone trabeculae begin to form between 5 and 10 days after distraction, soon become aligned with osteoblasts, and continue to grow as long as distraction force is applied. This characterization may help in any exogenous involvement with growth factors to improve bone quality.