Determinación de los parámetros idóneos de la distracción osteogénica de la mandíbula. Estudio experimental / Determination of mandibular distraction osteogenesis most suitable parameters. An experimental study

Resumen Antecedentes: Respecto a la distracción osteogénica (generación ósea inducida), con mayor o menor éxito han sido descritos diversos protocolos para el manejo del período de latencia, velocidad de distracción y período de consolidación. Objetivo: Entender mejor el proceso de la distracción mandibular y establecer los factores determinantes y sus tiempos óptimos. Material y métodos: Se estudiaron 27 perros sometidos a distracción osteogénica unidireccional, bilateral de la mandíbula. Los procesos de distracción se aplicaron con seis variantes, dos por cada factor (período de latencia, período de distracción y velocidad de distracción). Se estudiaron los cambios mediante biopsias del hueso y radiografías de la zona a los 0, 7, 14, 21, 45 y 55 días del proceso. Resultados: Los parámetros de distracción osteogénica más eficientes fueron período de latencia de cinco días, período de consolidación de seis semanas, 1 mm diario de velocidad de distracción para distancias menores a 20 mm y 3 mm diarios para distancias mayores. Conclusiones: El estudio histológico secuencial permitió observar la aparición de los elementos celulares (osteocitos, osteoclastos, matriz osteoide, trabeculado, etcétera) y su participación en el tejido de granulación, el hueso neoformado y el hueso maduro compacto.

Abstract Background: Distraction osteogenesis is a process of induced bone generation. Various protocols have been described for the management of the latency period, distraction speed and consolidation period, with greater or lesser success. Objective: To better understand the process of mandibular distraction and establish the determining factors and their optimal times. Material and methods: Twenty-seven dogs were studied, which had 54 distractors placed and that underwent unidirectional, bilateral mandibular distraction osteogenesis. The distraction processes were applied using six variants, two for each factor: latency period, distraction period and distraction speed. The changes were examined by means of bone biopsies and X-rays of the area at 0, 7, 14, 21, 45 and 55 days of the process. Results: The most efficient osteogenic distraction parameters were a latency period of five days, a consolidation period of six weeks, distraction speed of 1 mm/day for distances of less than 20 mm, and 3 mm/day for longer distances. Conclusions: The sequential histological study allowed to observe the appearance of cellular elements (osteocytes, osteoclasts, osteoid matrix, trabeculate, etc.) and their participation in granulation tissue, newly-formed bone and compact mature bone.

Application and accuracy assessment of a novel 3D-printed osteotomy guide in anterior maxillary segmental distraction osteogenesis / 上海交通大学学报（医学版）

Objective·To evaluate the effects of anterior maxillary segmental distraction osteogenesis(AMSDO)in treating sagittal maxillary hypoplasia in cleft lip and palate(CLP)patients and to report a 3D-printed surgical guide to facilitate the osteotomy.Methods·Twelve patients with CLP who underwent AMSDO were included in this study.Virtual osteotomy was performed in a 3-dimensional model and the osteotomy line were fabricated into a tooth-borne surgical guide by using 3D-printing technique.Lateral cephalograms taken before surgery(T0),at the end of consolidation(T1)and six months after consolidation(T2)were used to evaluate the effects of AMSDO.The accuracy of the osteotomy guide was measured by superimposing the postoperative CT data to virtual planning.Results·All the patients went through surgery without serious complications.SNA and overjet changed significantly both from T0 to T1 and from T0 to T2.ANB,facial convexity,and palatal length changed without significance from T0 to T1 and from T0 to T2.SNB remained stable.All the variables remained relatively stable from T1 to T2.The anteroposterior linear root-mean-square deviation(RMSD)between planning and actual results was 0.90 mm,while the angular RMSD in the sagittal plane was 5.07°.Conclusion·AMSDO is an effective treatment for maxillary hypoplasia secondary to CLP.The accuracy of this 3D-printed osteotomy guide is clinically acceptable,and this can simplify the surgery with fewer complications.

A study on the animal model preparation and early histological changes of trans-sutural distraction osteo-genesis / 实用口腔医学杂志

Objective:To establish an animal model of trans-sutural distraction osteogenesis in SD rats.Methods:A self-designed V-shaped distraction device(distractor)was fabricated with the traction force(N)of 0,1.3,2.2,3.0,4.3 and 5.0 corresponding to the distraction length(mm)of 5,4,3,2,1 and 0 respectively,meeting the trans-sutural distraction osteogenesis requirements in skull of 5-week-old SD rats.The distractor was plased into the sagittal suture of 12 SD rats.Continuous sampling was conducted 1,3,5 and 7 days respectively(n=3)after operation.The tissue changes in the trans-sutural distraction area were observed by HE and Masson's trichrome staining.Inflammation levels were determined using Arg-1 immunofluorescence staining.The early angiogenesis was clarified through co-staining with CD31 and EMCN.Results:A stable trans-sutural distraction osteogenesis model was estab-lished,5 mm distraction osteogenesis width was observed completely within 7 days of distraction.Significant new bone formation was observed at 7 days after operation.Arg-1 expression increased and was concentrated at the bone margins,overlapping with the areas of new bone formation.EMCN expression gradually decreased,and by day 7 CD31 was predominant,indicating the basic maturation of blood vessels.Conclusion:This study successfully constructed a stable and effective trans-sutural distraction osteogenesis animal model,and provides an experimental basis for the investigation of its early continuous histological changes.

Effect of tibial nerve injury on treatment of tibial single-plane osteotomy and bone transport / 中国组织工程研究

BACKGROUND:Peripheral nerves play an important role in bone metabolism.In clinical practice,the specific impact of nerve injury on bone transport technology needs further study. OBJECTIVE:To investigate the effect of tibial nerve injury on the treatment of tibial slip by single-plane osteotomy. METHODS:Thirty-two patients with tibial bone defects admitted to Tangshan Second Hospital from May 2011 to June 2022 were selected.According to the presence or absence of tibial nerve injury,patients were divided into the tibial nerve injury group(n=16)and the non-tibial nerve injury group(n=16).Both groups were treated with single-plane osteotomy and bone slip.After treatment,the patients were followed up to collect the mineralization zone healing index,external fixation index,docking point healing and needle infection.After the removal of external fixation,the bone healing and functional evaluation were evaluated by a classification of the Association for the Study and Application of the Method of Ilizarov(ASAMI). RESULTS AND CONCLUSION:(1)All 32 patients were followed up for(25.28±4.79)months.There were no significant differences in bone healing time,external fixation time,healing index and external fixation index between the two groups(P＞0.05).Needle infection occurred in two cases of the tibial nerve injury group and one case of the non-tibial nerve injury group,all of which were PALEY I,and there was no significant difference between the two groups(P＞0.05).The non-union rate of the occlusal end of the tibial nerve injury group was 31%,and that of the non-tibial nerve injury group was 13%;there was no statistical difference between the two groups(P＞0.05).The excellent and good rate of ASAMI bone healing score in the two groups was 100%;the excellent and good rate of limb score was 81%in the tibial nerve injury group and 94%in the non-tibial nerve injury group;there was no statistical difference between the two groups(P＞0.05).(2)Our research shows that tibial nerve injury has no significant effect on the mineralization speed,external fixation time,union of the occlusal end,infection of the needle tract,and the quality of bone formation in the mineralized area of the single-plane osteotomy.

Mechanism by which alendronate promotes rapid mandibular distraction osteogenesis in rabbits / 中国组织工程研究

BACKGROUND:Some studies have found that local application of alendronate can promote osteogenesis,but less is reported on the process of distraction osteogenesis. OBJECTIVE:To observe the promoting effect of alendronate on rapid mandibular distraction in a rabbit model and explore its possible mechanism. METHODS:Thirty-six male New Zealand white rabbits were randomly divided into groups A,B and C(n=12 per group)after operation and rapid distraction(3-day delay period followed by 3-day distraction at 1.5 mm/12 hours).At the 1st,3rd and 7th days of the consolidation period,animal were injected with 200 μg/kg alendronate in group A and 100 μg/kg alendronate in group B,while those in group C were treated as controls.CT scanning and dual energy X-ray bone mineral density measurement were performed at 4 and 8 weeks of the consolidation period.After the radionuclide scanning was completed at the 4th week,several animals were sacrificed and the samples were collected for western blot assay and tartrate resistant acid phosphatase staining.A three-point bending test was performed after the animals were sacrificed at the 8th week. RESULTS AND CONCLUSION:CT results showed that bone formation in the distraction space of group B was significantly better than that in groups A and C.At the 4th week,the bone mineral density in group B was(0.092±0.010)g/cm2,which was 1.26 times higher than that in group A(P＜0.001)and 1.28 times higher than that in group C(P＜0.001).At the 8th week,the bone mineral density in group B was(0.175±0.029)g/cm2,which was 1.38 times higher than that in group A(P＜0.001)and 1.45 times higher than that in group C(P＜0.001).Tartrate resistant acid phosphatase staining showed that the number of osteoclast-like cells in group C were 2.83 times more than that in group A(P＜0.001)and 2.21 times more than that in group B(P＜0.001).The radionuclide intensity was higher in group C than in groups A and B.Western blot assay results showed that the expression of Runx2 was significantly stronger in group B than in groups A and C.The maximum biomechanical load in group B was(158.48±23.21)N,which was 1.26 times higher than that in group A(P=0.007)and 1.31 times higher than that in group C(P=0.003).To conclude,the low concentration of alendronate may promote rapid distraction osteogenesis of the rabbit mandible by inhibiting osteoclast signals.

Risk factors for first weaning failure following mandibular distraction osteogenesis in pediatric patients with Pierre Robin sequence: a nested case-control study / 中华麻醉学杂志

Objective:To identify the risk factors for the first weaning failure following mandibular distraction osteogenesis in pediatric patients with Pierre Robin sequence (PRS).Methods:Clinical data of pediatric patients with PRS who underwent mandibular distraction osteogenesis from January 2018 to February 2023 were collected, including sex, age, premature birth, birth weight, surgical weight, cleft palate, syndrome type PRS, laryngeal/tracheobronchial malacia, simple congenital heart disease, complex congenital heart disease, preoperative mechanical ventilation, preoperative pulmonary infection, blood albumin concentration, difficulty in tracheal intubation under a visual laryngoscope, surgical duration, postoperative ventilator-associated pneumonia, duration of mechanical ventilation at first weaning, and traction length at first weaning. Children in whom the first postoperative machine withdrawal failed were included in observation group and matched to control cases(control group) in a 1∶4 ratio. The risk factors of which P values were less than 0.05 would enter the logistic regression analysis to stratify the risk factors for postoperative weaning failure. Results:There were significant differences in birth weight, cleft palate, duration of mechanical ventilation and traction length at first weaning, rate of combined cleft palate, preoperative pulmonary infection rate, rate of preoperative mechanical ventilation, and rate of postoperative ventilator-associated pneumonia between the two groups ( P<0.05). Binary logistic stepwise regression analysis showed that the preoperative mechanical ventilation ( OR=18.154, 95% CI 3.971-82.990, P<0.001) and postoperative ventilator-associated pneumonia ( OR=36.942, 95% CI 1.307-1043.985, P=0.034) were independent risk factors for first weaning failure after mandibular distraction osteogenesis, while birth weight gain ( OR=0.225, 95% CI 0.076-0.668, P=0.007) was a protective factor for first weaning failure ( P<0.05). Conclusions:Preoperative mechanical ventilation and postoperative ventilator-associated pneumonia are independent risk factors and birth weight gain is a protective factor for first weaning failure following mandibular distraction osteogenesis in pediatric patients with PRS.

The airway management and treatment of newborns with micrognathia and laryngomalacia / 临床耳鼻咽喉头颈外科杂志

Objective:To explore the perioperative airway management and treatment of newborns with micrognathia and laryngomalacia. Methods:From January to December 2022, a total of 6 newborns with micrognathia and laryngomalacia were included. Preoperative laryngoscopy revealed concomitant laryngomalacia. These micrognathia were diagnosed as Pierre Robin sequences. All patients had grade Ⅱ or higher symptoms of laryngeal obstruction and required oxygen therapy or non-invasive ventilatory support. All patients underwent simultaneous laryngomalacia surgery and mandibular distraction osteogenesis. The shortened aryepiglottic folds were ablated using a low-temperature plasma radiofrequency during the operation. Tracheal intubation was maintained for 3-5 days postoperatively. Polysomnography（PSG） and airway CT examination were performed before and 3 months after the surgery. Results:Among the 6 patients, 4 required oxygen therapy preoperatively and 2 required non-invasiveventilatory support. The mean age of patients was 40 days at surgery. The inferior alveolar nerve bundle was not damaged during the operation, and there were no signs of mandibular branch injury such as facial asymmetry after the surgery. Laryngomalacia presented as mixed type: type Ⅱ+ type Ⅲ. The maximum mandibular distraction distance was 20 mm, the minimum was 12 mm, and the mean was 16 mm. The posterior airway space increased from a preoperative average of 3.5 mm to a postoperative average of 9.5 mm. The AHI decreased from a mean of 5.65 to 0.85, and the lowest oxygen saturation increased from a mean of 78% to 95%. All patients were successfully extubated after the surgery, and symptoms of laryngeal obstruction such as hypoxia and feeding difficulties disappeared. Conclusion:Newborns with micrognathia and laryngomalacia have multi-planar airway obstruction. Simultaneous laryngomalacia surgery and mandibular distraction osteogenesis are safe and feasible, and can effectively alleviate symptoms of laryngeal obstruction such as hypoxia and feeding difficulties, while significantly improving the appearance of micrognathia.

Compresión-distracción en el tratamiento de pseudoartrosis de tibia distal utilizando el aparato de Ilizarov: reporte de casos / Compression-distraction in the treatment of distal tibial no union using the Ilizarov apparatus: case report / Compressão-distração no tratamento da pseudoartrose distal da tibia com Ilizarov: relato de caso

El método de Ilizarov, con sus diferentes variantes y mediante la utilización de su aparato, desarrollado en la década del 50, continúa vigente, sobre todo en el tratamiento de las complicaciones de fracturas, principalmente aquellas vinculadas a la infección y a las dificultades de la consolidación. Reportamos 2 pacientes adultos con diagnóstico de pseudoartrosis hipertrófica, rígida, con deformidad, sin infección activa y sin dismetría, tratados mediante el método de distracción y compresión realizado con el aparato de Ilizarov. En ambos casos se logró la alineación y consolidación del miembro con escasas complicaciones.

The Ilizarov method, with its different variants and using its apparatus, developed in the 1950s, is still valid, especially in the treatment of fracture complications, mainly those linked to infection and consolidation difficulties. We report 2 adult patients with a diagnosis of hypertrophic, rigid nonunion, with deformity, without active infection and without dysmetria, treated by the distraction and compression method performed with the Ilizarov device. In both cases, the alignment and consolidation of the limb was achieved with few complications.

O método de Ilizarov, com suas diferentes variantes e pelo uso de seu aparato, desenvolvido na década de 1950, ainda é válido, principalmente no tratamento de complicações de fraturas, principalmente aquelas ligadas à infecção e dificuldades de consolidação. Relatamos 2 pacientes adultos com diagnóstico de pseudoartrose hipertrófica, rígida, com deformidade, sem infecção ativa e sem dismetria, tratados pelo método de distração e compressão realizado com o dispositivo de Ilizarov. Em ambos os casos, o alinhamento e a consolidação do membro foram alcançados com poucas complicações.

Effect of local gene therapy on expression of Wnt3a and β-catenin in callus of distraction gap during mandibular distraction osteogenesis in rabbits / 中华医学美学美容杂志

Objective:To investigate the effect of electroporation-mediated local gene therapy on the expression of Wnt3a and β-catenin in callus of distraction gap during mandibular distraction osteogenesis of rabbits.Methods:The experiments were conducted in the laboratory of the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University from September 2019 to December 2019. Forty eight New-Zealand rabbits were randomly divided into control group (group A), gene therapy group (group B) and normal saline group (group C), with 16 rabbits in each group. After bilateral mandible osteotomy and distractors were implanted, the distractors were activated at a speed of 0.8 mm/d on 4th day, postoperatively, and lasted for 7 days, followed by consolidation period. Group A distracted only, group B was subject to local injection of recombinant plasmid pIRES-hBMP2-hVEGF165 in the distraction gap and electroporation stimulation at the beginning of activation distractors; and group C local injection of the same dose of normal saline in the distraction gap and electroporation stimulation at the beginning of activation distractors. Four animals in each group were sacrificed on the day at the end of distraction, 7th, 14th, 28th days of consolidation period, respectively. The callus in the distraction gap was taken for immunohistochemical staining and RT-PCR to detect the expression of Wnt3a and β-catenin, and image analysis was performed. SPSS 22.0 statistical software was used for data analysis.Results:Immunohistochemical staining showed that Wnt3a and β-catenin were mainly located in the cytoplasm and nuclei of fibroblasts, chondrocytes and osteoblasts in callus tissue. Immunohistochemistry and RT-PCR showed that the expression of Wnt3a and β-catenin reached a peak at the end of distraction. With the disappearance of distraction tension, the expression of Wnt3a and β-catenin gradually decreased. After gene therapy intervention, the expression of Wnt3a and β-catenin was significantly increased, and the expression of Wnt3a and β-catenin in group B was the highest at each time point, with statistically significant difference compared with groups A and C ( F=96.3, P<0.01). Conclusions:Gene therapy promotes the expression of Wnt3a and β-catenin in the callus of distraction gap, regulating the balance of the bone reconstruction system and thus promoting the formation of new bone in the distraction gap.

One-stage biplanar osteotomy correction of angulation and shortening deformity of the lower extremity after epiphyseal injury of the distal femur with a monorail external fixator / 中华实用儿科临床杂志

Objective:To investigate the clinical effectiveness of one-stage biplanar osteotomy correction of angulation and shortening deformity of the lower extremity after epiphyseal injury of the distal femur with a monorail external fixator.Methods:The data of 5 patients (2 males and 3 females) with angulation and shortening deformity in the lower extremity after epiphyseal injury of the distal femur were retrospectively analyzed.The patients underwent monorail external fixator assisted one-stage osteotomy correction of the distal femur and distraction osteogenesis of the middle and upper femur in Zhengzhou Orthopeadics Hospital from May 2017 to December 2019.The mean age was 13.6 years old (range: 10 to 17 years old). The affected limbs were shortened by 5.1 cm on average (range: 3.9 to 6.5 cm). The average angulation deformity of the distal femur was 24.9° (range: 17.0°to 30.5°). The mechanical lateral distal femoral angle (mLDFA), the mechanical posterior distal femoral angle (mPDFA), the mechanical axis deviation (MAD), the range of motion (ROM) of the knee, and the length of the lower limbs before surgery and at the final follow-up were measured and analyzed.Results:All patients were followed up for 22 months on average (range: 15 to 32 months). For all the 5 patients, the mechanical axis was well realigned, mLDFA, mPDFA, and MAD returned to normal range, and the length of the affected limb achieved the goal as planned before the surgery.Besides, the affected limbs were lengthened by 5.6 cm on average (range: 3.9 to 8.0 cm), and the median healing index was 35.6 d/cm (range: 29.0 to 45.0 d/cm). The bone callus in the distraction area and the osteotomy end were well healed at the final follow-up, as indicated by the X-ray results.At the end of the distraction period, the flexion ROM of the knee in all patients reached basically 90°.By the final follow-up, all patients had a normal knee ROM.No vascular or nerve injury, dislocation of hips or knee joints, re-fracture after disassembly, deep infection and other complications were observed in all patients.Conclusions:One-stage biplanar osteotomy correction of angulation and shortening deformity of the lower extremity after epiphyseal injury of the distal femur with a monorail external fixator is safe and feasible.The method requires no multiple operations and improves the tolerance of patients during the treatment period.

Distracción osteogénica del tercio medio facial. Reporte de dos casos clínicos / Distraction osteogenesis of the midface. Two clinical cases report

La corrección quirúrgica de grandes asimetrías faciales son un desafío para el equipo quirúrgico. En dichos casos, los resultados de la corrección utilizando técnicas quirúrgicas convencionales son limitados, lo que hace necesario la utilización de otras herramientas terapéuticas. La distracción ósea (DO) es una de ellas, pues permite el estiramiento controlado del callo óseo previamente creado mediante osteotomías. La DO permite realizar cambios en el posicionamiento óseo de gran envergadura, favoreciendo el crecimiento óseo como mecanismo de acción. El objetivo de este artículo es describir los resultados quirúrgicos de DO intraoral del tercio medio facial utilizado en dos pacientes con severas asimetrías faciales asociadas a malformaciones de origen genético. Se relata el diagnóstico, la planificación, las herramientas tecnológicas utilizadas, técnica quirúrgica y los resultados obtenidos.

Surgical correction of major facial asymmetries is a challenge for the surgical team. In such cases, treatment results from conventional surgical techniques are limited, which requires using other therapeutic tools. Bone distraction is one of them, as it allows controlled stretching of the bone callus previously developed through osteotomies. Distraction osteogenesis allows making changes in large bone positioning, favoring bone growth as an action mechanism. This article aims to describe the surgical results of intraoral distraction osteogenesis of the midface used in two patients with severe facial asymmetries related to congenital malformations. Diagnosis, planning, technological tools, surgical techniques, and results obtained are explained.

Perioperative evaluation and management of neonates with Pierre-Robin sequence / 中华实用儿科临床杂志

Objective:To summarize the clinical characteristics of neonates with Pierre-Robin sequence (PRS) who received mandibular distraction osteogenesis (MDO), in order to provide a basis for perioperative evaluation and management.Methods:Data of neonates diagnosed with PRS and receiving MDO in the Department of Neonatology, Guangzhou Women and Children′s Medical Center between December 2016 and December 2019 were collected for a retrospective study.According to the types of respiratory support needed before surgery, they can be categorized into 3 groups: the invasive ventilation group, the noninvasive ventilation group, the oxygen therapy/positioning therapy group.According to the usage of sedative and analgesic drugs after surgery, they were categorized into 2 groups: the sedative-analgesic group(Fentanyl Citrate and Midazolam) and the single sedative group(Midazolam alone).Results:A total of 31 children were admitted, 22 cases of whom received MDO at an age of (22.09±8.42) d, including 11 cases in the invasive ventilation group, 5 cases in the non-invasive ventilation group, and 6 cases in the therapy/positioning therapy group before surgery; there was statistical significance in severe respiratory distress (81.8% vs.60.0% vs.0) and feeding difficulties (100.0% vs.80.0% vs.50.0%) among the 3 groups (all P<0.05), while there was no difference in laryngomalacia rate(63.6% vs.20.0% vs.33.3%), non-gain in weight before surgery(81.8% vs.80.0% vs.66.7%), postoperative ventilation duration[(7.5±3.4) d vs.(7.2±5.3) d vs.(6.9±4.1) d]and hospital stay[(36.3±9.3) d vs.(34.1±0.3) d vs.(33.8±7.5) d] (all P>0.05). Among these 22 patients, there were 9 cases in the sedative-analgesic group, and 13 cases in the single sedative group.Compared with the single sedative group, cases in the sedative-analgesic group had significantly lower extubation rate (0 vs.15.4%) and shorter hospital stay[(32.3±5.2) d vs.(39.8±7.3) d], and the difference were statistically significant (all P<0.05). Besides, there were no differences in postoperative ventilation duration[(7.4 ± 3.9) d vs.(7.6 ± 4.2) d]between both groups ( P>0.05). The postoperative remission rate of airway obstruction was 100%. Conclusions:MDO in children in their neonatal period could achieve favorable efficacy.The duration of postoperative ventilator support and hospital stay in children with severe airway obstruction could not be prolonged compared with children with mild obstruction, and postoperative sedation and analgesic management can reduce the extubation rate.

Research progress on the reconstruction of mandibular defects in adolescents / 口腔疾病防治

@#Mandibular defects in adolescents are mostly caused by surgical resection of benign and malignant tumors, trauma and jaw inflammation. The reconstruction of mandibular defects in adolescents is challenging. In addition to solving the problem of jaw reconstruction in adults, some clinical factors, including the influence of surgery on the growth of donor and recipient areas, the long-term effects of reconstruction, and the outcome of bone grafts, must also be considered. At present, the main reconstructive methods include autogenous bone grafts and distraction osteogenesis. Autogenous bone grafts are still the gold standard due to their long-term effects. Favorable growth potential after repair was shown in adolescent cases of mandibular reconstruction with fibula flap. Normal occlusion was restored, and a long-term stable effect was achieved in cases of condylar reconstruction with costal cartilage. The safety and clinical effects of distraction osteogenesis have been confirmed, but the long-term effects of large-scale mandibular defects are still uncertain. In addition, other tissue engineering techniques also have good application prospects for the repair and reconstruction of adolescent mandible defects, but more in-depth basic research and more extensive clinical trials should be performed to verify the efficacy.

Kaempferol promotes osteogenic differentiation of mouse bone marrow mesenchymal cells under tension stress via the mTORC1 signaling pathway / 口腔疾病防治

Objective @#To investigate the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway molecules during the process by which kaempferol (Kae) promotes osteogenic differentiation of mouse bone marrow mesenchymal cells (BMMCs) under cyclic and uniaxial tension.@*Methods @#BMMCs isolated and cultured in vitro were subjected to uniaxial dynamic tension with a 10% shape variable. The appropriate concentration of Kae was selected by cytotoxicity testing. The endogenous mTOR signal was inhibited by pp242. Four hours after traction, alkaline phosphatase (ALP) and osteocalcin (OCN) were detected by chemical colorimetry and ELISA, and the relative concentration of intracellular calcium was detected by flow cytometry. Phosphorylation of mTOR, 4E/BP1, and ribosomal protein S6 kinases (S6K), which are the main molecules of the endogenous mTORC1 signaling pathway, and expression of osteogenic transcription factors (Runx2 and Osterix) were detected by western blotting (WB), and mRNA expression levels of the above factors were detected by qRT-PCR.@*Results @# The cytotoxicity test showed that 10 μmol/L Kae had little inhibitory effect on cell proliferation but had the strongest osteogenic ability. Four hours after stretching, Kae effectively promoted the osteogenic differentiation of BMMCs. The expression of ALP was （153.04 ± 18.72） U/mg, the expression of OCN was （1.64 ± 0.25） U. The mRNA and protein levels of Runx2 and Osterix were upregulated, and the intracellular calcium content was decreased. The mRNA and protein phosphorylation of mTOR and S6K was upregulated, and the opposite effect was observed with 4E/BP1. After pp242 was added to inhibit mTOR signaling, mTOR and S6K mRNA and protein phosphorylation were downregulated, but 4E/BP1 mRNA and protein phosphorylation was upregulated. The osteogenic differentiation of BMMCs was also significantly inhibited, mRNA and protein expression of Runx2 and Osterix were significantly downregulated, ALP and OCN expression were downregulated, and intracellular calcium content was increased. @* Conclusion@#Kae promotes osteogenic differentiation of mouse BMMCs under uniaxial dynamic tension through the mTORC1 signaling pathway.

Study of rrPDGF-BB gene modified BMSCs in promoting distraction osteogenesis of rat femur / 中华显微外科杂志

Objective:To investigate the therapeutic effect of rat bone marrow mesenchymal stem cells (BMSCs) transfected with recombinant rat platelet-derived growth factor BB (rrPDGF-BB) gene on the distraction osteogenesis.Methods:From October, 2019 to June, 2020, 48 batches of BMSCs were cultured from 48 young SD rats, 24 of which were transfected with rrPDGF-BB gene by lentivirus. Meanwhile, other 72 male adult SD rats were randomly selected to establish the right femoral distraction osteogenesis model. The rats were equally divided into 3 groups. PBS, BMSCs without intervention and BMSCs transfected with rrPDGF-BB gene were injected into the distraction space of each group of rats assigned as Blank group, Negative group and Experimental group, respectively. Results of the experiment were evaluated by means of imaging and immunohistochemistry. P<0.05 indicated a statistically significant difference. Results:The cultured BMSCs grew well. The expression of CD34(0.1%) and CD45(2.8%) in the third generation of BMSCs was low, and that of CD29 (95.1%) was high, which was consistent with the phenotype of BMSCs described in literatures. After transfection, the expression of green fluorescence gradually increased with the extension of transfection time, confirming the success of transfection. After 14 days, all rats reached the expected distance of distraction. The rats were observed at assigned time points in 2, 4 and 8 weeks. The photos of femur specimen showed that continuous callus could be seen in the experimental group, the hardness and colour were close to the normal bone tissue, and the activity of the distraction space was poor, which was lower than that of the blank group. X-ray examination showed that there were more new callus in the experimental group, and the bone marrow cavity was re-canalized earlier than that of the blank group; Micro-CT examination, in sagittal plane, showed that the distraction space of the experimental group healed well, the broken end was connected, and the recanalization of bone marrow cavity was earlier than that of the blank group; Micro-CT parameters of each group showed that trabecular thickness[(0.297±0.005) mm], trabecular number [(1.663±0.032) mm], bone volume fraction[(59.832±2.187)%] and bone mineral density[(0.586±0.014) g/cm 3] of the experimental group were the greatest, while trabecular separation[(0.399±0.051) mm] of the experimental group was the smallest. There was statistical difference between each group( P < 0.05); HE staining and VEGF immunohistochemistry showed that the vessels and chondrocytes formed earlier and were more in the experimental group than that in the blank group. In 8 weeks, the new callus joined into one piece under the microscope in the experimental group, and the bone marrow cavity was re-canalized with a large number of red blood cells. Conclusion:Studies have shown that BMSCs transfected with rrPDGF-BB gene can promote the formation of callus in the distraction area of rats, shorten the mineralisation time of new callus, and promote the maturation of new bone in the area of distraction osteogenesis.

Alargamiento óseo con clavo intramedular magnético experiencia preliminar y lecciones aprendidas / Bone lengthening with magnetic intramedullary nail preliminary experience and learned lessons

OBJETIVOS: Mostrar resultados, complicaciones y lecciones aprendidas utilizando el clavo intramedular magnético (IML, Intramedullary Magnetic Lengthener) en un grupo de pacientes sometidos a alargamiento óseo. PACIENTES Y MÉTODOS: Entre enero 2017 y diciembre 2019, 9 pacientes (15 segmentos), edad entre 15 y 39 años, fueron sometidos a alargamiento óseo con IML: 5 pacientes tuvieron alargamiento femoral bilateral por talla baja, 1 paciente se sometió a alargamiento de Piernas bilateral por Tibia vara y acortamiento mesomélico y 3 recibieron alargamientos femorales unilaterales por discrepancia de longitud de extremidades. Todos fueron operados por el mismo cirujano, con técnica standard. Se indicó kinesiterapia al menos 5 veces por semana durante la fase de distracción. RESULTADOS: En todos se logró el objetivo de alargamiento planteado. No hubo complicaciones intra ni postoperatorias graves (TVP, TEP, Embolia grasa), ni fallas del sistema distractor. Un paciente desarrolló contracturas articulares de ambas rodillas por no adhesión a Kinesiterapia. Ninguno requirió aporte de injerto óseo, sin embargo en 2 pacientes de alargamiento de Fémur bilateral, se presentó deformidad en varo, que hizo necesario recambio a clavo convencional y un paciente desarrolló una parálisis transitoria del Nervio Peroneo común. CONCLUSIONES: El advenimiento de los IML significó un gran avance en el campo de la osteogénesis por distracción, sin embargo, aún se trata de un procedimiento complejo, que debe ser planificado cuidadosamente para minimizar los riesgos y complicaciones. Una selección meticulosa del paciente y la evaluación física y psicológica previa, son fundamentales para el éxito del procedimiento. Los casos bilaterales requieren de un seguimiento cercano, por el riesgo de falla del implante.

objective: We show our results, complications and lessons learned using the Intramedullary Magnetic Lengthener (IML) in a group of patients who were subjected to bone lengthening. PATIENTS AND METHODS: Between January 2017 and December 2019, 9 patients (15 segments), aged between 15 and 39 years, underwent bone lengthening with IML: 5 patients had bilateral femoral lengthening due to short stature, 1 patient had bilateral leg lengthening due to Tibia vara and mesomelic shortening and 3 had unilateral femoral lengthening for limb length discrepancy. All were operated by the same surgeon, with standard technique. Physical therapy was indicated at least 5 times per week during the distraction phase. RESULTS: In every case, the proposed lengthening amount was achieved. There were no serious intraoperative or postoperative complications (DVT, Pulmonary Embolism, Fat Embolism), nor failures of the distractor system. One patient developed knee joint contracture due to non-adherence to Physical therapy. None required bone grafting, however, in 2 patients with bilateral Femur, a varus deformity appeared, which required nail exchange with a conventional trauma nail. One case developed a transit common Peroneal Nerve palsy. CONCLUSIONS: IMLs represent a great advance in the bone lengthening realm, however, it is still a complex procedure, which must be carefully planned to minimize risks and complications. Meticulous patient selection and prior physical and psychological evaluation are essential to the success of the procedure. Bilateral cases need a closer follow up, because implant failure is a potential risk.

Planejamento virtual em cirurgia ortognática para tratamento de assimetria: relato de caso / Virtual planning in orthognathicsurgey for assimetrytreatment: case report

Introdução: Os casos de assimetria facial são um desafio para tratamento no âmbito da cirurgia Bucomaxilofacial, devido a alteração craniofaciais nos três planos do espaço (Pitch,Yaw e Roll). Estes termos são utilizados para o planejamento da cirurgia ortognática e são essenciais para o planejamento virtual, A utilização da tecnologia neste sentido vem sendo cada vez mais empregada devido a sua previsibilidade de resultado tanto nos casos convencionais como nos mais desafiadores como os das assimetrias faciais. Este artigo visa relatar o planejamento virtual para a correção de um caso de assimetria através da cirurgia ortognática. Relato de caso: Paciente pediátrico leucoderma, do sexo masculino com 5 anos, possui limitação na abertura de boca, desvio da mandíbula para o lado direito com tempo de evolução de 5 meses. O procedimento consistiu na remoção da massa fibrótica através do acesso de Al Kayat. Após o procedimento cirúrgico o paciente foi submetido a uma série de sessões de fisioterapia agressiva. Considerações finais: A associação da remoção da massa fibrótica ou do bloco anquilótico e a fisioterapia intensa no pósoperatório propiciaram um resultado satisfatório, devolvendo a função mandibular do paciente... (AU)

Introduction: The temporomandibular ankylosis consists in mandibular movements limitation and is characterized as complete fusion of mandibular condyle to articular fossa or as a formation of a fibrotic mass in the region. Case Report: Pediatric male patient, white, 5 year-old, had a mouth opening limitation, mandibular deviation to the right side with 5 mouths of evolution. The procedure consisted in the removal of the fibrotic mass through the Al-Kayat approach. After the surgical procedure the patient was submitted to a series of aggressive physiotherapy sessions. Final considerations: The association of the removal of the fibrotic mass or the ankylotic bloc to intense physiotherapy in the post operatory provides a satisfactory result, restoring patient´s mandibular function... (AU)

Four-dimensional space events of fracture healing / 中国组织工程研究

BACKGROUND: Fracture fixation and surgical procedures have a very important impact on the final outcome of fracture healing, but the adverse outcome of fracture healing is the result of the combined action of surgical procedures and a series of four-dimensional space events. OBJECTIVE: To explore the four-dimensional space events in fracture healing. METHODS: China National Knowledge Infrastructure and Medline were retrieved, with the key words of “fracture healing, femoral fracture, stress shielding, fracture and blood flow” in Chinese and English. Retrieval of relatively macroscopic factual descriptions corresponds to the four-dimensional space events of fracture healing process, including logically supported and refuted evidence. Combined with literature review, the main four-dimensional space events after fracture fixation were analyzed. RESULTS AND CONCLUSION: The main four-dimensional space events after fracture fixation include blood flow tides, mechanical and biological impulses, grinding disc effect of small gap in hard tissue, stress shielding effect and four-dimensional space drift effect of internal fixation material. Fractures and surgical trauma are accompanied by months of super-compensatory blood flow tides, so there is no ischemia in the macro-level after fracture surgery, but the grinding disc effect will occur in the small gap of hard tissue under unstable condition, resulting in contusion injury and micro-ischemia in the fracture gap. Stress shielding effect caused by too strong fixation is an important reason for refracture after internal fixation removal and bone atrophy and thinning after internal fixation. The small axial drift of plate fixation screw may have important theoretical significance. It has “intelligent” axial dynamic effect, which can make the stress shared by plate gradually decrease with the healing of fracture. Discussing the four-dimensional space events of fracture healing will provide basic logic for the regulation of fracture healing and distraction osteogenesis.

The role of the mTORC1 signaling pathway during osteogenic differentiation of mouse bone marrow mesenchymal cells under tension stress / 口腔疾病防治

Objective@# To investigate the expression of the mTORC1 signaling pathway during the osteogenic differentiation of mouse bone marrow mesenchymal cells (BMMSCs) under cyclic uniaxial tension and explore its possible role.@*Methods @# The BMMSCs of mice were affected by uniaxial dynamic tensile force. Western blot was used to detect the expression changes of major molecules (mTOR, Raptor, S6K) in the endogenous mTORC1 signaling pathway at 0, 1, 2, 4, and 8 hours after stretching. Chemical colorimetry, ELISA and PCR were used to detect alkaline phosphatase (ALP), osteocalcin (OCN) and Runx2 mRNA, respectively. Then, inhibition, activation and control groups were established by administration of the drugs PP242, MHY1485 and PBS, respectively. Two hours after the stress, the expression of S6K was detected by western blot, and the expression of the osteogenic signal was continuously detected by the above methods.@*Results @#Western blot analysis showed that the main molecules of the mTORC1 signaling pathway were all expressed within 8 hours after traction, and the highest expression was 2 hours after the stress. Compared with those in the control group, the ALP activity and OCN expression decreased and the Runx2 mRNA levels increased after the mTORC1 signal pathway was inhibited (P ＜ 0.001); ALP activity and OCN expression increased after the mTORC1 signal pathway was activated, while the Runx2 mRNA levels decreased (P ＜ 0.001). @*Conclusion @#The mTORC1 signaling pathway participates in the osteogenic differentiation of mouse BMMSCs under tension. The osteogenesis of BMMSCs under cyclic uniaxial tension would be enhanced if the mTORC1 signaling pathway was activated.

Tracheostomy and mandibular distraction in acute sleep apnea

Severe restriction of airway volume in the orofacial region, caused by temporomandibular joint (TMJ) ankylosis, may lead to obstructive sleep apnea (OSA). If the TMJ ankylosis is progressive, rarely, the caregivers may fail to notice the problem. Such patients may have only symptoms of snoring, daytime sleepiness, fatigue, inability to concentrate, and irritability. At times, emergency tracheostomy may be needed to increase the oxygen supply. Distraction osteogenesis (DO) is a less invasive surgical technique in the management of such OSA by correcting the reduced airway space. In DO, the angulation of the distractors and the pace of activation determine the success of the neo-generation of segments of bone. The formation of a well-corticated mandibular canal (MC) in the newly generated bone is an evidence of the success of the procedure. Such bilateral formation of the MC is not reported from this part of the world. We report a case of a 4-year-old boy who was struggling with OSA due to TMJ ankylosis. He was successfully treated by bilateral mandibular DO. The formation and cortication of the MC is discussed with emphasis on the neural regeneration.