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.

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.

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.

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

Mandibular functional reconstruction using internal distraction osteogenesis

OBJECTIVE: To study the potential and advantages of internal distraction osteogenesis in mandibular functional reconstruction. METHODS: Three types of mandibular distractors were used in eight patients with various mandibular defects due to tumor or cyst resection. The average age of the patients was 31.5 years old (ages ranged from 8 to 54 years). For two patients with ramus defects, specially designed distractors were used to restore the normal ramus height. In two other patients, specially designed trifocal distractors were used. In three patients, vertical distractors were used. RESULTS: All the mandibles were successfully reconstructed in accordance with the direction and distance designed before operation except in one patient. In that patient the distal 23 mm defect failed to be corrected because of loosening of transport block fixation screws. CONCLUSIONS: Mandibular defects can be successfully corrected using internal distraction osteogenesis. Performing mandibular reconstruction using distraction osteogenesis is best done at the time of tumor or cyst resection.

Advancement of maxillary anterior segment by distraction osteogenesis for severe maxillary retrusion in cleft lip and palate

Background Maxillary anterior segmental distraction osteogenesis （MASDO） is a recently used method for correction of severe maxillary retrusion in cleft lip and palate （CLP） patients.In this article,we evaluated the feasibility of MASDO using rigid external distraction （RED） and rapid orthodontic tooth movement to correct severe maxillary retrusion in CLP patients.Methods Fourteen male and five female complete CLP patients between the ages of 18 and 22 years （mean age 19.7 years） at the time of distraction,with severe maxillary retrusion,were treated with the rigid external distraction （RED） device after maxillary anterior osteotomy.Rapid orthodontic tooth movement was started one week after the MASDO.Standard profile photographic,cephalometric films were obtained preoperatively and after therapy.Sella-nasion-point A （SNA） and Sella-nasion-point B （SNB） angles were measured to reflect changes in maxillary and mandibular position,and the distance between anterior nasal spine and posterior nasal spine （ANS-PNS） was measured to represent the maxillary dental arch length.Results The SNA angle increased from an average of 74.6° （range 73.0°-78.0°）,preoperatively,to 83.4° （range 78.6°-88.0°） after the RED was removed （P ＜0.01）.All cases of severe maxillary retrusion were improved.Nine patients＇ profiles became harmonious after therapy.One patient had a bimaxillary protrusion deformity and needed further surgery.The regenerate alveolar crest and edentulous space on both segments was almost completely eliminated after rapid orthodontic tooth movement.Conclusion MASDO with the RED system and rapid orthodontic tooth movement is a successful way of correcting severe maxillary retrusion in CLP patients.

Rapid tooth movement through distraction osteogenesis of the periodontal ligament in dogs

Background Animal models are needed for the study of rapid tooth movement into the extraction socket through distraction osteogenesis of the periodontal ligament. Methods Modified distraction devices were placed on eight dogs between the first and third mandibular premolars on the left sides; similar placement of traditional straight wise appliances on the right sides served as the control. The experimental distractors were activated （0.25 mm/d） twice a day and the control devices were activated （100 g） for two weeks with consolidation periods at weeks two, three, six, and ten. Two dogs were sacrificed at each consolidation time point; rates and patterns of tooth movement, loss of anchorage, and periapical films were evaluated, and the affected premolars and surrounding periodontal tissues were decalcified and examined histologically. General observations, X-ray periapical filming and histology examination were performed. Results Distal movement （（3.66±0.14） mm） measured two weeks after modified distraction exceeded that achieved using the traditional device （（1.15±0.21） mm; P 〈0.05）. Loss of anchorage was minimally averaged （0.34±0.06） mm and （0.32±0.07） mm in the experimental and control sides, respectively. By radiography, apical and lateral surface root resorptions on both sides were minimal. Alveolar bone lesions were never evident. Fibroblasts were enriched in periodontal ligaments and bone spicules formed actively along directions of distraction. Conclusions The canine model is suitable for the study of rapid tooth movement through distraction osteogenesis of the periodontal ligament. The technique accelerates tooth movement, periodontal remodeling, alveolar bone absorption, and may induce fibroblast formation, as compared to the traditional orthodontic method, without adversely affecting root absorption, bone loss, tooth mobility and anchorage loss.

Effect of a combination of local flap and sequential compression- distraction osteogenesis in the reconstruction of post-traumatic tibial bone and soft tissue defects

Background Treatment of extensive post-traumatic composite bone and soft tissue defects remains a complicated therapeutic problem and a challenge for surgeons. We investigated the application of local flaps and Ilizarov osteogenesis in the reestablishment of severe combined defects of tibial bone and soft tissue. Methods Sixteen patients with bone and soft tissue defects were included. The mean age of the patients was 31.5 years. The average time from injury to initial surgery was 14.4 weeks. The average soft tissue and bone defect sizes were 92.9 cm2 and 8.7 cm, respectively. Local flaps were created to reconstruct the soft tissue defects. The Ilizarov external fixator or the Orthofix Limb Reconstruction System was used to reconstruct bony defects using delayed distraction osteogenesis. Results Two myocutaneous flaps and 14 reverse island flaps were applied. All transferred flaps survived. Fifteen patients healed with equal leg length, and one healed with a residual leg-length discrepancy of 1.5 cm. One patient with an Ilizarov external fixator developed ankle joint stiffening and a pin-track infection that was successfully treated with oral antibiotics. No patient developed pin loosening. All patients walked without assistance. Fifteen patients returned to their work, and one lost her job. The results were evaluated using the Paley bone and functional assessment scores. The bone assessment results were excellent in 14 and good in two patients. Functional assessment scores were excellent in 13, good in two, and fair in one patient. Conclusion The combination of local flaps and sequential distraction osteogenesis can be used for successful reconstruction of defects of incorporated bone and soft tissue.

Adipose-derived stem cells transfected with pEGFP-OSX enhance bone formation during distraction osteogenesis

This study was designed to investigate the effects of local delivery of adipose-derived stem cells （ADSCs） transfected with transcription factor osterix （OSX） on bone formation during distraction osteogenesis. New Zealand white rabbits （n=54） were randomly divided into three groups （18 rabbits per group）. A directed cloning technique was used for the construction of recombinant plasmid pEGFP-OSX, where EGFP is the enhanced green fluorescence protein. After osteodistraction of the dght mandible of all experimental rabbits, rabbits in group A were treated with ADSCs transfected with pEGFP-OSX, group B with ADSCs transfected with pEGFP-N1, and group C with physiological saline. Radiographic and histological examinations were processed after half of the animals within each group were humanely killed by injection of sodium pentothal at Week 2 or 6 after surgery. The distraction bone density was measured as its projectional bone mineral density （BMD）. Three parameters were measured, namely, the thickness of new trabeculae （TNT）, and the volumes of the newly generated cortical bone （NBV1） and the cancellous bone （NBV2） of the distracted regions. Good bone generation in the distraction areas was found in group A, which had the highest BMD, TNT, and NBV in the distraction zones among the groups. There was no significant difference in bone generation in the distraction areas between groups B and C. The results indicate that the transplantation of ADSCs transfected with pEGFP-OSX can effectively promote bone generation during distraction in vivo.

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.

Mechanical regulation of bone regeneration during distraction osteogenesis

Distraction osteogenesis(DO)is a mechanobiological process of regenerating bone tissue by tension stress.DO is used clinically to lengthen bones or to treat critical size bone defects.Although DO provides satisfactory results in many cases,the prolonged period of treatment remains a major challenge that needs to be overcome.Various attempts have been devoted to accelerating bone regeneration during DO.One common approach is manipulation of the applied mechanical loading by altering distraction strategies.In this article,we reviewed relevant in vivo animal studies exploring the effects of changing mechanical environments,by varying distraction parameters(e.g.,rate and frequency)or adding compression loading,on bone regeneration in DO.We further presented how the mechanically-regulated bone regeneration process during DO could be simulated by in silico models incorporating mechano-regulatory tissue differentiation rules.A comprehensive review of those in vivo and in silico studies may not solely provide important references for development of improved DO protocols in clinic,but also promote a deeper understanding of the mechanobiological mechanism of bone regeneration.

3D打印导板在上颌骨前段牵引成骨中的应用及精度测量

目的·评估上颌骨前段牵引成骨(anterior maxillary segmental distraction osteogenesis,AMSDO)在治疗唇腭裂继发上颌骨发育不足中的作用以及3D打印导板在截骨中的精度。方法·收集12例接受了AMSDO治疗的唇腭裂患者的病例资料。手术前在患者的三维模型上进行虚拟手术,并通过3D打印将患者的截骨线制成牙支持式导板。术前(T0)、巩固期结束(T1)以及巩固期后6个月(T2)进行头影测量以评估AMSDO的效果及稳定性。导板的精度通过术后即刻CT与术前设计CT进行叠加,并通过计算位置和角度误差进行评估。结果·所有患者都顺利完成了牵引治疗,没有发生严重的并发症。SNA(S-N-A角)和覆盖从T0到T1以及T0到T2都发生了显著的改变。ANB(A-N-B角)、面部突度、硬腭长度都发生了变化,但是差异没有统计学意义。SNB(S-N-B角)基本没有发生变化。从T1到T2,所有的参数都没有发生明显变化。导板截骨精度在矢状向的线性均方根误差为0.90 mm,角度均方根误差为5.07°。结论·AMSDO是治疗唇腭裂继发上颌骨发育不足的一种有效方法。3D打印的截骨导板具有良好的精度,在减少手术并发症的同时降低了手术的难度。