Mandibular Distraction Osteogenesis for the Treatment of an Obstructive Sleep Apnea Patient with Orthognathic Anomaly:A Case Report and Literature Review

Objective: skeletal advancement in order to improve the airway dimensions is known as one of the most effective surgical theraphy for treating obstructive sleep apnea (OSA). Distraction osteogenesis (DO) can be a better treatment alternative in some selected cases similar to our patient. Using custom made distractors can make this technique more safe and successful. Study Design: Surgically assisted rapid palatal expansion (SARPE), bilateral intraoral mandibular distraction osteogenesis (MDO) and orthodontic treatment were tried to a 20-year-old OSA patient with orthognathic anomaly. For mandibular distraction, custom made distractors were used. Results: The initial AHI of the patient was 23.3. At the end of the treatment it decreased to 8.7. Conclusions: Distraction osteogenesis could be a better alternative than the conventional orthognathic surgery in this kind of selected patients. Customization of the distraction devices can contribute to making this procedure safer and more successful.

Expression of Bone-related Genes in Bone Marrow MSCs after Cyclic Mechanical Strain: Implications for Distraction Osteogenesis

Aim Understanding the response of mesenchymal stem cells （MSCs） to mechanical strain and their consequent gene expression patterns will broaden our knowledge of the mechanobiology of distraction osteogenesis. Methodology In this study, a single period of cyclic mechanical stretch （0.5 Hz, 2,000 με） was performed on rat bone marrow MSCs. Cellular proliferation and alkaline phosphatase （ALP） activity was examined. The mRNA expression of six bone-related genes （Ets-1, bFGF, IGF-Ⅱ, TGF-β, Cbfal and ALP） was detected using real-time quantitative RT-PCR. Results The results showed that mechanical strain can promote MSCs proliferation, increase ALP activity, and up-regulate the expression of these genes. A significant increase in Ets-1 expression was detected immediately after mechanical stimulation, but Cbfal expression became elevated later. The temporal expression pattem of ALP coincided perfectly with Cbfal. Conclusion The results of this study suggest that mechanical strain may act as a stimulator to induce differentiation of MSCs into osteoblasts, and that these bone-related genes may play different roles in the response of MSCs to mechanical stimulation.

Trifocal distraction osteogenesis for reconstruction of skull defect

Objective: To apply trifocal distraction osteogenesis in canine model of skull segmental defects and to provide reference for clinical treatment. Methods: Six labrador dogs were selected in this study and divided into observation group and control group randomly. Each group contained 3 dogs. Skull segmental defects models were established by surgery, and dogs in bservation group received trifocal distraction osteogenesis treatment. Bone density was observed and compared between two groups during treatment. Results: There were no significant difference in bone density between two groups on th 1st day ( P>0.05). The bone density of observation group on the 30th day, and 60th day were higher than that of control group ( P<0.01). Conclusions: Trifocal distraction osteogenesis has significant clinical effect, and it would be widely used in clinical treatment.

Immunomodulatory effects and mechanisms of distraction osteogenesis

Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.

Histological changes following surgically-assisted rapid tooth movement through resistance reduction and distraction osteogenesis in dogs

Objective To investigate the histological changes of rapid tooth movement in dogs treated by resistance reduction and distraction osteogenesis,aiming to establish an animal model and further to reveal the remodeling mechanism of rapid tooth movement. Methods A total of 8 local hybrid dogs were selected as subjects for this study. The second pre-molar was extracted on both sides. The experimental side underwent alvelor surgery for resistance reduction and a home-made tooth-borne intraoral distraction device was installed for rapid tooth movement,while for the other side (control side) only tooth-borne intraoral distraction device was used for rapid tooth movement. The longest active force-delivery span was 2 weeks,followed by 6-week retention. The distance between the moved tooth and anchor unit was recorded weekly,and radiography was performed for each side before and after distraction. The surrounding tissues including periodontal ligament and alveolar bone were sectioned for histological analysis. Results The average distance of tooth movement was 3.55mm on the experimental side and 1.11mm on the control side. The rate of tooth movement was notably higher (P<0.01) and no significant apical root resorption was detected by X-ray on the experimental side. The active alvelor bone remodeling was found on the tension and pressure sides. However,there was no significant difference between the experimental side and the control side after the retention period. Conclusion The rate of orthodontic tooth movement can be accelerated through resistance reduction and periodontal distraction without any unfavorable effects but at minimal anchorage loss.

Management of Mandibular Hypoplasia Using Distraction Osteogenesis Technique

By using distraction osteogenesis technique, 3 cases of mandibular hypoplasia were treat ed by home made and German made jaw distractors: including one patient suffered from bilateral ankylosis of temporo mandibular joint and 2 patients from deficiency of mandible. The duration of distraction osteogenesis was one month. The bone distractor was removed 3 months after operation. Satisfactory results were obtained in all 3 cases. Distraction osteogenesis can successfully be used in mandibular functional reconstruction and has much more advantages than traditional technique.

Correction of post ankylotic facial asymmetry with bimaxillary distraction osteogenesis—Case report

Facial asymmetry can be acquired or congenital. Patients with facial asymmetry are not always functionally disturbed by the malfunction but are usually very much disturbed by their external appearance. Depending on the degree of asymmetry and deformation, the surgical procedure may vary in complexity and extent. The extent of surgery can range from a genioplasty procedure to bimaxillary osteotomy, concomitant with augmentation surgery, genioplasty and craniofacial implants along with mandibular distraction. In severe cases, the soft tissue structures on the affected side may constitute an incredible resistance to stretching and can make the surgery considerably more difficult and liable to relapse. Here we represent a case of post ankylotic facial asymmetry with occlusal cant which was treated by bimaxillary distraction osteogenesis. Simultaneous mandibular and maxillary distraction corrected the facial asymmetry without disturbing the pre-existing compensated dental occlusion, and so there was no need for prolonged and difficult orthodontic treatment.

Maxillary Distraction Osteogenesis

Background: Distraction Osteogenesis is popular for long bones. And nowadays it has found its role in facial bone deficiency treatments. Purpose: We used our special designed Distractor for advancement of Maxillary deficiencies in cleft lip and palate patients. The purpose of this paper is to compare the treatment of hypoplastic, posteriorly retruded maxillary of cleft palate patients using distraction osteogenesis vs. Le fort I orthognathic surgery for length of advancement, stability and relapse, growth after distraction and soft tissue expansion and soft tissue profile changes. Meterial & Methods: In group A only Le fort I and surgical maxillary advancement sometimes with bone graft were done. In group B we used our special Distractor for Distraction Osteogenesis and advancement of the Maxillary bone. Demographic data, length of retrusion of maxilla, time length of treatment, length of advancement and relapse, SNA and SNB angles were measured and included in the study. The results were compared in each group before and after advancement and between both groups. The rate of distraction was 0.5 mm twice per day to achieve normal occlusion with 2 mm overcorrection more than calculated measures. The devices removed after 10 weeks as latency period. Results: The SNA increased at the end of distraction (p < 0.001), with no significant relapse indicating stability at 1 year after treatment. The total length of advancement in group A was 17 ± 4 mm and in group B was 20 ± 3 mm. The difference between before and after measurements in each group was significant (p = 0.002, p = 0.003 respectively). The mean length of relapse in group A was 3 ± 1 mm and in group B was 1 mm. Discussion: For the deformities and retrusions less than 7 - 8 mm, the Orthognatic surgery is the treatment of choice, however for more retrusions (>10 mm) we recommend Distraction Osteogenesis, and it preferred to start it soon in younger ages.

The osteogenetic rate in alveolar bone remodeling induced by distraction osteogenesis of the periodontal ligament

Objective: To observe osteogenetic rate of alveolar bone on the tension side in orthodontic tooth movement through distraction osteogenesis of the periodental ligament quantificationally. Methods: The experiment was carried in 6 dogs. The left side of jaws of each one was set as test or control side, and the other side was control or test side. On the control side, the first premorlar was moved by traditional method on the test side. A self-made distraction device was used on the test side. The newly formed alveolar bone on the tension side of moved tooth was labeled by serial tetracycline fluorochrome. Sections were observed by fluorescence microscope and pictured. Newly formed bone was measured by computer image analysis. Results: The quantity of newly formed bone was significantly different between the two methods. Newly formed bone in rapid tooth movement by distraction osteogenesis of the periodental ligament was more than that in traditional method. Conclusion: The distraction through periodental ligament could induce more rapid bone formation and excite higher osteogenetic activity than traditional method.

Upper Airway Changes after Maxillary Distraction Osteogenesis in Cleft Lip and Palate Patients

Purpose: To measure the upper airway changes associated with maxillary distraction osteogenesis in cleft lip and palate patients in the immediate post operative period and 12 months later. Materials and Methods: Seven patients with repaired cleft lip and palate (CLP) presented with severe maxillary hypoplasia. They were examined initially at T1 predistraction phase. Records taken included radiographs (orthopantograms OPG, lateral cephalometric, posteroanterior). Cephalometric analysis was done to evaluate the upper airway. Mean age is 17 years and the reverse overjet > 6 mm. They underwent maxillary Le Fort I distraction using external rigid distracters (RED). Cephalometric analysis to evaluate the upper airway was repeated at the end of the consolidation phase T2 and twelve months after distractor removal T3. Results: The range of maxillary advancement was between 8 - 15 mm (mean 9 mm). The anteroposterior distance of the superior velopharynx (PPS) and middle velopharynx (SPPS) increased at T2. A small amount of reduction in these values was recorded at T3. The inferior velopharynx (MPS) and the oropharynx (IPS, EPS) showed minimum increase in anteroposterior distance in only two patients at T2 and no change at T3. Conclusion: All seven patients showed clinical improvement in the upper airway and an increase in the upper airway values on lateral cephalometric radiographs.

Application of a pre-filled tissue expander for preventing soft tissue incarceration during tibial distraction osteogenesis

BACKGROUND Bone transport and distraction osteogenesis has been widely used to treat bone defects after traumatic surgery,but,skin and soft tissue incarceration can be as high as 27.6%.AIM To investigate the efficacy of inserting a tissue expander to prevent soft tissue incarceration.METHODS Between January 2016 and December 2018,12 patients underwent implantation of a tissue expander in the subcutaneous layer in the vicinity of a tibial defect to maintain the soft tissue in position.A certain amount of normal saline was injected into the tissue expander during surgery and was then gradually extracted to shrink the expander during the course of transport distraction osteogenesis.The tissue expander was removed when the two ends of the tibial defect were close enough.RESULTS In all 12 patients,the expanders remained intact in the subcutaneous layer of the bone defect area during the course of transport distraction osteogenesis.When bone transport was adequate,the expander was removed and the bone transport process was completed.During the whole process,there was no incarceration of skin and soft tissue in the bone defect area.Complications occurred in one patient,who experienced poor wound healing.CONCLUSION The pre-filled expander technique can effectively avoid soft tissue incarceration.The authors’primary success with this method indicates that it may be a valuable tool in the management of incarcerated soft tissue.

Adipose Derived Stem Cell on the Regeneration of Irradiated Mandible of Adult Rabbit Submitted to Distraction Osteogenesis

Purpose： To evaluate the effect of adipose derived mesenchymal stem cell （ADSC） on the regeneration of irradiated mandible submitted to distraction osteogenesis on adult rabbits. Methods： Ten adult rabbits were selected and the dorsal fat was harvested for isolation, dissociation and culture of adipose derived adult mesenchymal stem cells. The mandibles were irradiated on a single dose of 20 Gy. After 30 days the animals underwent mandibular lengthening by distraction osteogenesis. After 10 mm of lengthening, the animals were distributed into two groups. Saline solution （1 mL） was injected the control group, and supplemented with ADSC, on the study group. After 4 weeks the mandibles were removed and evaluated by tomography and histomorphometric analysis. Histomorphometric was obtained and statistical analysis done by Mann-Withney test （p 〉 0.05）. Results： The tomography shows a significant improvement on the Hounsfield scale for lateral fibrovascular zone （114.5±9.7 control group to 148 ± 24, p = 0.0045） and central fibrovascular zone （37 ± 13.4 control group to 96 ±41.8 on study groupp = 0.0045）. The Histomorphometric analysis demonstrated an increase area of new bone formation. The mineralized area was of 61.2 ± 9.9% in the study group and 31.3 ± 10.6% in the control group （p = 0.0045） for the central fibrovascular zone, 79.± 9.1% in the study group and 39.1 ± 14.7 on control group for anterior fibrovascular zone （p = 0.0001） and 67.7± 12.9% in the study group and 38.4 ± 12.9% in control group for posterior fibrovascular zone （p = 0.0001）. Conclusions： The injection of adipose derived mesenchymal stem cell was effective to improve bone regeneration distraction callus on the irradiated mandible.

Ultrastructural and element spectrometric analysis of distraction osteogenesis for reconstruction of cleft palate in rhesus macaque model

Objective To study the ultrastructure and Ca/P clement spectrometry of distraction osteogenesis(DO) for reconstruction of cleft palate(CP),so as to explore the osteogenesis and remodeling of new bone in situ.Methods 23 rhesus macaques

Dentoalveolar changes following maxillary distraction osteogenesis

The purpose of this study was to compare the dentoalveolar changes produced when using two different intraoperative surgical procedures for maxillary distraction osteogenesis. Eight patients were assigned into two groups according to the surgical procedure: down-fracture (DF, n = 6) vs non-down-fracture (NDF, n = 2). Lateral cephalograms and 3-D models before and after maxillary distraction were analyzed. The Mann-Whitney U test was used to compare the differences in the amounts of advancement and dento-alveolar changes between the DF and NDF groups. The significance level was established at 0.05. Although a significantly greater amount of maxillary movement was observed in the DF group (10.0 mm ± 2.2) than in the NDF group (5.9 mm ± 2.3), significantly greater arch length (8.7 mm ± 5.2) and arch width changes (6.0 mm ± 1.0) were observed in the NDF group than in the DF group, (arch lengths 3.0 mm ± 1.1 and arch width changes 3.2 mm ± 2.0). A significantly greater amount of dental anchorage loss was observed in the NDF group. The use of the NDF procedure resulted in greater amounts of dental anchorage loss than resulted from the DF procedures when tooth-borne devices were used during maxillary distraction osteogenesis. The type of surgical procedure might play an important role in the amount and direction of the dental changes.

Sinomenine increases osteogenesis in mice with ovariectomyinduced bone loss by modulating autophagy

BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.AIM To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying mechanisms.METHODS For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor 3-methyladenine.In vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.RESULTS SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.CONCLUSION The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.

Case Report and Clinical Management of a Case of Osteogenesis Imperfecta Detected in the Prenatal Period

Osteogenesis imperfecta is a hereditary disease characterized by bone fragility due to a defect in type I collagen synthesis. The diagnosis is typically suspected based on suggestive ultrasound findings and confirmed through genetic studies. We present a case of osteogenesis imperfecta suspected during obstetrical ultrasound at 19 weeks’ gestation, which was later confirmed radiographically through computed tomography. Due to the severity of the condition, therapeutic termination of pregnancy was indicated.

Neurophysiological, histological, and behavioral characterization of animal models of distraction spinal cord injury: a systematic review

Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.

Distraction osteogenesis for correction of post ankylosis mandibular deformities

Temporomandibular joint ankylosis, a debilitating disease mainly affecting children, is characterized by progres- sive restriction of mouth opening and maxilla-mandibular developmental deformities. Craniofacial distraction osteo- genesis has been developed as a standard surgical strategy for rectification of craniofacial deformities. The purpose of this study was to assess mono-planar distraction devices for the correction of various mandibular asymmetries in patients with unilateral temporomandibular joint ankylosis who developed restricted mouth opening and mandibular retrognathia. All patients were treated using one-stage distraction osteogenesis followed by temporalis fascia inter- positional arthroplasty under general anesthesia. A significant increase in mandibular ramus and base length was observed. Although an increase in anterior lower facial height was observed, it was not significant statistically. A decrease in posterior lower facial height and corpus was observed. Oblique distraction with angular osteotomy allowed lengthening of both the ramus and corpus, yielding satisfactory results and hence eliminating the need of secondary surgery. In conclusion, univector internal distractors are effective for correction of multi-planar mandib-ular deficiencies by optimizing its placement through meticulous planning.

Super enhancers targeting ZBTB16 in osteogenesis protect against osteoporosis

As the major cell precursors in osteogenesis, mesenchymal stem cells(MSCs) are indispensable for bone homeostasis and development. However, the primary mechanisms regulating osteogenic differentiation are controversial. Composed of multiple constituent enhancers, super enhancers(SEs) are powerful cis-regulatory elements that identify genes that ensure sequential differentiation. The present study demonstrated that SEs were indispensable for MSC osteogenesis and involved in osteoporosis development. Through integrated analysis, we identified the most common SE-targeted and osteoporosis-related osteogenic gene,ZBTB16. ZBTB16, positively regulated by SEs, promoted MSC osteogenesis but was expressed at lower levels in osteoporosis.Mechanistically, SEs recruited bromodomain containing 4(BRD4) at the site of ZBTB16, which then bound to RNA polymerase IIassociated protein 2(RPAP2) that transported RNA polymerase Ⅱ(POL Ⅱ) into the nucleus. The subsequent synergistic regulation of POL Ⅱ carboxyterminal domain(CTD) phosphorylation by BRD4 and RPAP2 initiated ZBTB16 transcriptional elongation, which facilitated MSC osteogenesis via the key osteogenic transcription factor SP7. Bone-targeting ZBTB16 overexpression had a therapeutic effect on the decreased bone density and remodeling capacity of Brd4^(fl/fl)Prx1-cre mice and osteoporosis(OP) models.Therefore, our study shows that SEs orchestrate the osteogenesis of MSCs by targeting ZBTB16 expression, which provides an attractive focus and therapeutic target for osteoporosis.

Zuo Gui Wan Promotes Osteogenesis via PI3K/AKT Signaling Pathway:Network Pharmacology Analysis and Experimental Validation

Objective Osteogenesis is vitally important for bone defect repair,and Zuo Gui Wan(ZGW)is a classic prescription in traditional Chinese medicine(TCM)for strengthening bones.However,the specific mechanism by which ZGW regulates osteogenesis is still unclear.The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis.Methods A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells(BMSCs).Results In total,487 no-repeat targets corresponding to the bioactive components of ZGW were screened,and 175 target genes in the intersection of ZGW and osteogenesis were obtained.And 28 core target genes were then obtained from a PPI network analysis.A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress,metal ions,and lipopolysaccharide.Additionally,KEGG pathway enrichment analysis revealed that multiple signaling pathways,including the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway,were associated with ZGW-promoted osteogensis.Further experimental validation showed that ZGW could increase alkaline phosphatase(ALP)activity as well as the mRNA and protein levels of ALP,osteocalcin(OCN),and runt related transcription factor 2(Runx 2).What’s more,Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT,and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002.Finally,the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002.Conclusion ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.