Role Of Distraction Osteogenesis Research Articles

Enhanced Bone Regeneration through Regulation of Mechanoresponsive FAK-ERK1/2 Signaling by ZINC40099027 during Distraction Osteogenesis.

Background: Focal adhesion kinase (FAK) is activated by mechanical stimulation and plays a vital role in distraction osteogenesis (DO), a well-established but lengthy procedure for repairing large bone defects. Both angiogenesis and osteogenesis contribute to bone regeneration during DO. However, the effects of ZINC40099027 (ZN27), a potent FAK activator, on angiogenesis, osteogenesis, and bone regeneration in DO remain unknown. Methods: The angiogenic potential of human umbilical vein endothelial cells (HUVECs) was evaluated using transwell migration and tube formation assays. The osteogenic activity of bone marrow mesenchymal stem cells (BMSCs) was assessed using alkaline phosphatase (ALP) and alizarin red s (ARS) staining. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence staining were used to assay angiogenic markers, osteogenic markers, and FAK-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In vivo, a rat tibia DO model was established to verify the effects of ZN27 on neovascularization and bone regeneration using radiological and histological analyses. Results: ZN27 promoted the migration and angiogenesis of HUVECs. Additionally, ZN27 facilitated the osteogenic differentiation of BMSCs, as revealed by increased ALP activity, calcium deposition, and expression of osteogenesis-specific markers. The ERK1/2-specific inhibitor PD98059 significantly hindered the effects of ZN27, suggesting the participation of FAK-ERK1/2 signaling in ZN27-enhanced angiogenesis and osteogenesis. As indicated by improved radiological and histological features, ZN27 induced active angiogenesis within the distraction area and accelerated bone regeneration in a rat DO model. Conclusion: Our results show that ZN27 targets FAK-ERK1/2 signaling to stimulate both angiogenesis and osteogenesis, and ZN27 accelerates bone regeneration in DO, suggesting the therapeutic potential of ZN27 for repairing large bone defects in the mechanobiological environment during DO.

Role of Distraction Osteogenesis in the Management of Postankylotic Deformity.

Distraction osteogenesis (DO) has evolved in maxillofacial surgery and gained popularity due to the limitations of orthognathic surgery in gross asymmetry cases. The primary aim of the paper was to determine if the use of DO for the management of severe deformities of the mandible secondary to temporomandibular joint ankylosis can achieve optimal results, with or without genioplasty, based on cephalometric norms. The secondary aim of this study was to evaluate the complications associated with DO in this group of patients. Six patients with postankylotic deformity were included. Both internal and external devices were used for an average mandibular corpus lengthening of 15mm with adjunctive procedure genioplasty. All patients had excellent outcome in terms of profile, functional occlusion, and mouth opening without deviation. Two patients had primary genioplasty showed excellent compliance and 2 as secondary at the time of device removal. Complications noted were, difficulty in vector control during distraction, paresthesia, occlusal discrepancy, scarring, and relapse of 2 to 3mm. Preorthodontics and postorthodontics were done in all patients to settle the occlusion, which was stable after 2-year follow-up. Case series shows such gross deformities pose a greater challenge due to undergrowth, gross midline shift, and discrepancy between soft and hard tissue growth pattern and the desired results can be achieved by precise planning. Genioplasty at the time of device placement has definitive positive effect on patient compliance. Though orthognathic surgery has a definitive role in minor deformity, whereas in gross deformities DO with precise planning using 3-dimensional model and vector controlled technique offers excellent outcome.

A systematic review on the outcome of distraction osteogenesis in TMJ ankylosis

IntroductionTMJ ankylosis (TMJa) management by arthroplasty alone fails to address the deformity and the compromised airway. Distraction osteogenesis (DO) can offer a pragmatic solution to TMJa. The aim of the study was to generate evidence towards the role of DO in TMJa, evaluate its efficiency and develop an algorithm for use of DO in TMJa. Material and methodsThe research question was formulated using the PICOS statement for reporting guidelines in systematic reviews, where the efficiency of DO was evaluated in terms of mouth opening, correction of facial deformity and asymmetry, airway correction, and its long term effects. Results1130 articles reported DO as a treatment modality for TMJ ankylosis, of which 32 prospective studies, 16 retrospective and 2 RCTs were included in the study. DO was used for mandibular distraction in 45 studies and for simultaneous maxillamandibular distraction in only five studies. An algorithm for use of DO in TMJa was developed. ConclusionAlthough DO has proven its application in TMJ ankylosis cases, its best use is for correction of obstructive sleep apnoea. Relapse causing loss of posterior ramal height is a concern after transport DO. Prearthroplastic DO appears to best correct mandibular deformity. A maxillomandibular deformity requires simultaneous maxillomandibular distraction. However, a metanalysis is still awaited for effectiveness of DO in TMJ ankylosis.

Management of obstructive sleep apnoea: an update on the role of distraction osteogenesis.

This article reviews the current literature on the use of distraction osteogenesis as a treatment for patients with obstructive sleep apnoea (OSA). We reviewed the indications, surgical protocols and outcomes for distraction osteogenesis in paediatric and adult OSA cases described in the literature. There is evidence that distraction osteogenesis is effective in treating children with OSA as a result of underdevelopment of jaws such as those with craniofacial syndromes. Distraction osteogenesis appears to be the only available treatment that prevents tracheostomy in some of these cases, or allows decannulation after distraction. For adult OSA patients, distraction osteogenesis is reported to be reserved for challenging cases such as OSA as a consequence of temporomandibular joint ankylosis. It is used where conventional orthognathic surgery is not feasible. The studies reported high success rate/cure rate of OSA after distraction osteogenesis. Technological advances such as three-dimensional printing assist the execution of an accurate distraction process. Distraction osteogenesis appears to be an effective treatment for paediatric OSA patients with craniofacial anomalies, and is used in selected cases of adult with severe OSA. With the improvement in distraction device designs and computer technology, distraction osteogenesis may play a bigger role in the treatment of OSA.

Fak-Mapk, Hippo and Wnt signalling pathway expression and regulation in distraction osteogenesis.

To investigate the mechanism of mechanical stimulation in bone formation and regeneration during distraction osteogenesis. In this study, microarray technology was used to investigate the time course of bone-related molecular changes in distraction osteogenesis in rats. Real-time PCR and Western-blot analyses were used to confirm the expression of genes identified in microarrays. Meanwhile, we used a lentivirus vector to inhibit Fak expression, in order to identify the osteogenic effect of Fak and Fak-Mapk pathway during distraction osteogenesis. Several components of the Wnt and Hippo pathways were found to be up- or down-regulated during distraction osteogenesis by microarray. Meanwhile, it was found that Fak, Src, Raf-1, Erk1, Jnk and p38-Mapk were up-regulated during gradual distraction, compared with consolidation. To further determine whether Fak-Mapk pathway played an important role in distraction osteogenesis, Fak was disrupted with a lentivirus vector. The expressions levels of p-Fak, p-Erk1/2, p-JNK and p-p38Mapk were decreased. Meanwhile, a poor early and late osteogenesis effect was found in the shRNA-Fak group. It was inferred that the mechanical stimulus induces increased expression of Fak and activates Fak-Mapk pathway, by activation of Erk, Jnk and p38-Mapk pathway, and that Fak at least, in part, plays an important role in maintaining osteogenic effect by activating Fak-Mapk pathway during distraction osteogenesis.

Role of distraction osteogenesis in craniomaxillofacial surgery.

In the field of orthopedic surgery, distraction osteogenesis (DO) is well known for limb lengthening procedures or secondary corrective surgery in the fracture treatment of the extremities. The principle of gradual expansion of bone and surrounding soft tissues as originally described by G.A. Ilizarov is also applicable to the craniofacial skeleton when growth deficiency is present, and the patients affected by craniofacial or dentofacial anomalies may require distraction procedures. The surgical management is comparable. After osteotomy and the mounting of a specific craniomaxillofacial distraction device, active distraction is started after a latency phase of several days, with a distraction rate of up to 1 mm/day until the desired amount of distraction has been achieved. Subsequently, distractors are locked to provide appropriate stability within the distraction zone for callus mineralization during the consolidation phase of 3–6 months, which is followed by a further remodeling of the bony regenerate. After 14 years of clinical application, the role and significance of craniomaxillofacial DO are discussed after reviewing the files of all patients who were treated by craniomaxillofacial distraction procedures.

Systemic administration of lithium improves distracted bone regeneration in rats.

Lithium, popular in psychology field, has been recognized as an activator component of the canonical Wnt signaling pathway. The effect of lithium on osteogenesis or on the human fracture risk has been widely reported. However, little is known on its role in distraction osteogenesis to date. In this study, the effect of systematic administrated lithium on distraction osteogenesis in a rat model was investigated. The osteotomy was performed on the right tibia in 40 adult male Sprague-Dawley rats. Then they were randomly assigned into two equal groups (n = 20/group), which underwent Lithium or saline treatment through gastric gavage until the day they were killed. One week after the osteotomy, the tibias were distracted for 14 days (rate 0.6 mm/day). Following 8 weeks consolidation period, the distracted tibias in both groups were harvested and examined by X-ray plain radiography, histology, dual-energy X-ray absorptiometry, Micro-CT, and biomechanical tests. The results showed that lithium group possessed higher bone mineral density, more mature new bone tissue, and better regenerated bone mass continuity in the distraction gaps without any local or systemic adverse effects was encountered. This study suggested lithium could increase bony callus ossification volume and accelerate distracted tissue mineralization to facilitate bone regeneration in distraction gap.

The role of distraction osteogenesis in patients presenting with dento-facial deformity—An overview

Distraction osteogenesis is a novel clinical technique aimed at generating bone and associated soft tissue by incremental separation of the surgically separated bone segments. The technique has gained increasing popularity in managing severe dento-facial deformity since its application to the maxillo-facial region was first described. This article will provide an overview of the history of the technique, the biological basis of distraction osteogenesis, and its clinical application in the maxillo-facial skeleton.

The role of distraction osteogenesis in the management of craniofacial syndromes

Distraction osteogenesis (DO) has been established as a useful technique in the correction of skeletal anomalies of the long bones for several decades. However, the use of DO in the management of craniofacial deformities has been evolving over the past 20 years, with initial experience in the mandible, followed by the mid-face and subsequently, the cranium. This review aims to provide an overview of the current role of DO in the treatment of patients with craniofacial anomalies.

The Role of Distraction Osteogenesis in Children with Secondary Craniosynostosis after Shunt Operation in Early Infancy

Background: Secondary craniosynostosis rarely develops within several months in infants or children after shunt operations in early infancy. However, conventional operations (CO) such as fronto-orbital advancement and total skull reshaping have not been efficient enough to expand the intracranial volume in children with secondary craniosynostosis. Recently, distraction osteogenesis (DO) was reported to be effective in treating most craniosynostosis cases. Methods: We compared 9 children treated with DO and 3 children treated with CO who developed secondary craniosynostosis after shunt operation in early infancy. We measured the preoperative and follow-up head sizes with regard to head circumference, cephalometric intracranial volume, and intracranial volume estimated from the 3-dimensional computed tomogram. Results: The mean intracranial volumes expanded by 10.5% in the DO group 1 month after surgery and by 13.1% in the CO group on the immediate postoperative day. Further expansion was observed 6 months postoperatively, i.e. 10.3 and 4.7% in the DO and CO groups, respectively. Operation time and anesthesia time were significantly shorter in DO compared to CO patients, and the volumes of the blood transfusions were also less for DO patients. Conclusion: We suggest that DO is probably more efficient and safer than CO in expanding the intracranial volume in children with secondary craniosynostosis.

L519: Comprehensive Surgical Treatment of Cleft Lip and Palate Patients—Evidence- Based Discussion

Oral and maxillofacial surgeons play a critical role in the treatment of cleft lip and palate deformities. There are many controversies in the literature pertaining to different treatment modalities. This includes efficacy of presurgical orthopedic appliances, primary gingivoperiosteoplasty, the effect of different palatal repair techniques on speech production, the timing of alveolar bone grafting, and the role of distraction osteogenesis in this patient population. This eye-opener will explore these topics through a review of the pertinent literature.

Role of distraction osteogenesis in maxillofacial reconstruction

Background and Objectives: Distraction osteogenesis involves creation of unlimited quantities of living bone by gradual movement of two of more bony segments following their surgical separation. This technique was first developed for limb lengthening but recently was widely applied in craniomaxillofacial bone with satisfactory outcome. Several designs of the extra and intraoral distraction devices have been invented to serve for different area of the complex craniofacial bone. Intraoral designed devices seem to posses more advantages than extraoral devices, including minimal scarring, less cumbersome with more patient friendly acceptation.

Role of distraction osteogenesis in temporomandibular joint ankylosis: a case report

Cranio-mandibular ankylosis is characterized by the formation of a bony mass which replaces the normal articulation. For this reason, excision of this mass is not necessary for the release of ankylosis. In recent studies, mandibular distraction has been used to lengthen the retrognathic mandible of patients with TMJ ankylosis. The vertical ramal height is corrected and a pseudo joint is created. The aims of this poster are to show the use of distraction osteogenesis in ankylosis and to present a therapeutic option for the treatment of mandibular hypoplasia with unilateral ankylosis in the childhood to treat the ankylosis.

The role of distraction osteogenesis in mandibular reconstruction

Distraction osteogenesis is finding increasing application in the management of mandibular defects. It provides an alternative method of mandibular reconstruction in varied clinical settings, notably following trauma and ablation of malignant tumors. Many recent studies have explored modifications in surgical technique, refinements in device design, and experiments in animal models. This review attempts to discuss all of the above. In addition to managing the segmental mandibular gap, the vertical distraction technique is highly useful for increasing fibular bony height, allowing osseointegrated implant placement and dental rehabilitation. Variations in distraction planes, parameters and device placement have made it possible to tailor appropriate reconstructive strategies to the specific patient. Newer developments in distractor design and constituents, and the application of staged distraction procedures, have facilitated optimal management of the challenging defect. Distraction osteogenesis is a continually evolving field of research and study, and an aesthetically and functionally acceptable option for managing extensive mandibular defects, and those not amenable to conventional methods. It offers distinct advantages over other available reconstructive options, but does have its disadvantages. With further improvement in devices and technique, it has the potential of being much more widely used in the future.

Bone regeneration in limb lengthening

Purpose of review: Impaired bone healing is a major source of complications in limb lengthening. This review presents our recent understanding of bone healing biology and basic research for modulating bone healing in limb lengthening. Recent findings: Angiogenesis appears to play a major role in distraction osteogenesis with increased gene expression and upregulation of many angiogenic factors during the process. In-vivo and clinical studies have demonstrated the benefits of bone morphogenic protein, bisphosphonates, electromagnetic fields, and ultrasound to aid in bone healing during limb lengthening. Summary: The mechanisms of distraction osteogenesis continue to be studied using in-vivo models. Beneficial effects of growth factors, bisphophonates, electromagnetic fields and ultrasound have been demonstrated to enhance bone healing in in-vivo limb-lengthening models. Further clinical studies are needed to demonstrate their efficacy.

The role of bone morphogenetic proteins BMP-2 and BMP-4 and their related postreceptor signaling system (Smads) in distraction osteogenesis of the mandible.

Distraction osteogenesis has become a widely used clinical approach in the treatment of craniofacial and orthopedic disorders. The exact biological mechanism of bone formation remains illusive, however. The aim of this study was to evaluate the role of bone morphogenetic protein-2, bone morphogenetic protein-4, and transforming growth factor-beta superfamily-related postreceptor signaling glycoproteins Smads 1 through 5 in distraction osteogenesis. Twelve sheep randomly divided into two groups were distracted to 24 mm at 1 or 4 mm/d using a submandibular osteotomy and an external distractor. After a 5-week fixation period, the mandibles were harvested. Employing immunohistochemical techniques, the sections were investigated for the previous antigens. Osteoblasts and periosteal lining cells were strongly positive. The matrix did not stain for the antigens investigated. Osteocytes demonstrated weak staining for the antigens. No significant difference between the groups was noted. In fracture healing, bone morphogenetic proteins 2 and 4 have been localized to the cambial layer of the periosteum, where healing occurs by intramembranous ossification. Their diffuse staining of the osteoblasts in the distracted region supports a similar role in distraction osteogenesis, where bone formation is predominantly through intramembranous ossification. Furthermore, bone morphogenetic proteins 2 and 4 have been demonstrated to promote mesenchymal cell conversion to osteoblasts. This is similar to the process observed in distraction osteogenesis. The presence of related Smads confirms postreceptor activity of these bone morphogenetic proteins in the process of distraction osteogenesis. This study supports induction of bone morphogenetic proteins 2 and 4, their related postreceptor signaling system (Smads), and intramembranous bone formation associated with mechanical strain in distraction osteogenesis.

Cranial distraction osteogenesis in sheep using a totally implantable hydraulic mechanism: early results

Conventional distraction osteogenesis has been performed by using either percutaneous pins attached to a thread and screw mechanism, or a thread and screw mechanism that is implanted but still requires turning by a percutaneous instrument or device. In these situations there is always the risk of infection passing to the bone via the percutaneous connection. We have developed a totally implantable hydraulic mechanism, which is activated in much the same way as injection into the port of a tissue expander. Preliminary in vitro testing has suggested that our mechanism can produce sufficient force at appropriate rates of distraction to have a promising role in distraction osteogenesis. We examined the effect of osseous distraction on the cranial vault. Expansion of the cranial vault by distraction osteogenesis is not widespread in clinical practice, in part because of the risk of infective complications of the extra-dural space. We were, therefore, presented with an ideal opportunity both to test the new distraction device and to examine the effect of distraction osteogenesis on the cranial vault. A sheep animal model was used in a pilot study to test the plausibility and examine the physiology of cranial-vault distraction osteogenesis using a totally implantable hydraulic device. Two sheep had a device implanted in the temporal fossa so as to push the craniotomised cranial cap upwards. Distraction was performed for 13 days beginning 1 week after craniotomy. After 9 weeks of consolidation, 5.5 mm and 7.4 mm of new woven bone of normal cranial thickness were demonstrated.

The role of distraction osteogenesis in the reconstruction of the mandible in unilateral craniofacial microstomia.

The role of distraction osteogenesis in the reconstruction of the mandible in unilateral craniofacial microstomia.

The role of distraction osteogenesis in the reconstruction of the mandible in unilateral craniofacial microstomia.

The role of distraction osteogenesis in the reconstruction of the mandible in unilateral craniofacial microstomia.

The role of distraction osteogenesis in the reconstruction of the mandible in unilateral craniofacial microsomia.

The role of distraction osteogenesis in the reconstruction of the mandible in unilateral craniofacial microsomia.