Distraction osteogenesis for ulnar lengthening in Kienbock's disease.
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ABSTRACT:
SUBMITTER: Kawoosa AA
PROVIDER: S-EPMC2267598 | biostudies-other | 2007 Jun
REPOSITORIES: biostudies-other
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Project description:BackgroundDistraction osteogenesis (DO) is a surgical technique to promote bone regeneration which may require long duration for bone consolidation. Bone marrow-derived mesenchymal stem cells (MSCs) have been applied to accelerate bone formation in DO. However, the optimal time point for cell therapy in DO remains unknown. This study sought to determine the optimal time point of cell administration to achieve early bone consolidation in DO. We hypothesized that the ratio of circulating MSCs to peripheral mononuclear cells and the level of cytokines in serum might be indicators for cell administration in DO.MethodsUnilateral tibial osteotomy with an external fixator was performed in adult Sprague Dawley rats. Three days after osteotomy, the tibia was lengthened at 0.5 mm/12 h for 5 days. At first, 5 rats were used to analyze the blood components at 6 different time points (3 days before lengthening, on the day lengthening began, or 3, 6, 10, or 14 days after lengthening began) by sorting circulating MSCs and measuring serum levels of stromal cell-derived factor 1 (SDF-1) and interleukin 1β. Then, 40 rats were used for cell therapy study. A single dose of 5 × 105 allogeneic MSCs was locally injected at the lengthening site on day 3, 6, or 10 after lengthening began, or 3 doses of MSCs were injected at the three time points. Sequential X-ray radiographs were taken weekly. Endpoint examinations included micro-computed tomography analysis, mechanical testing, histomorphometry, and histology.ResultsThe number of circulating MSCs and serum level of SDF-1 were significantly increased during lengthening, and then decreased afterwards. Single injection of MSCs during lengthening phase (on day 3, but not day 6 or 10) significantly increased bone volume fraction, mechanical maximum loading, and bone mineralization of the regenerate. Triple injections of MSCs at three time points also significantly increased bone volume and maximum loading of the regenerates.ConclusionThis study demonstrated that bone consolidation could be accelerated by a single injection of MSCs during lengthening when the ratio of peripheral MSCs to mononuclear cells and the serum SDF-1 presented at peak levels concurrently, suggesting that day 3 after lengthening began may be the optimal time point for cell therapy to promote early bone consolidation.
| S-EPMC7083044 | biostudies-literature
Project description:Distraction osteogenesis is an effective method for generating large amounts of bone in situ for treating pathologies such as large bone defects or skeletal malformations, for instance leg-length discrepancies. While an optimized distraction procedure might have the potential to reduce the rate of complications significantly, our knowledge of the underlying mechanobiological processes is still insufficient for systematic optimization of treatment parameters such as distraction rate or fixation stiffness. We present a novel numerical model of lateral distraction osteogenesis, based on a mechanically well-controlled in vivo experiment. This model extends an existing numerical model of callus healing with viscoplastic material properties for describing stress relaxation and stimuli history-dependent tissue differentiation, incorporating delay and memory effects. A reformulation of appositional growth based non-local biological stimuli in terms of spatial convolution as well as remeshing and solution-mapping procedures allow the model to cope with severe mesh distortions associated with large plastic deformations. With these enhancements, our model is capable of replicating the in vivo observations for lateral distraction osteogenesis in sheep using the same differentiation rules and the same set of parameters that successfully describes callus healing in sheep, indicating that tissue differentiation hypotheses originally developed for fracture healing scenarios might indeed be applicable to distraction as well. The response of the model to modified distraction parameters corresponds to existing studies, although the currently available data is insufficient for rigorous validation. As such, this study provides a first step towards developing models that can serve as tools for identifying both interesting research questions and, eventually, even optimizing clinical procedures once better data for calibration and validation becomes available.
| S-EPMC5854389 | biostudies-literature
Project description:Mandibular distraction has revolutionized the treatment of Robin sequence associated with severe airway obstruction. The distraction technique remains the only intervention that directly corrects mandibular hypoplasia and the retropositioned tongue, providing efficient relief of airway stenosis. Multiple studies have demonstrated the efficacy of distraction in avoiding tracheostomy and decreasing the severity airway obstruction in this patient population. The benefit to avoiding tracheostomy and relieving airway obstruction is superior to that of tongue-lip adhesion. It is, therefore, not surprising that mandibular distraction has become the first-line intervention at many centers for the surgical treatment of Robin sequence. The complication profile associated with mandibular distraction appears low; the most common complication is infection, which can be treated by antibiotics alone. The severity of airway obstruction can be quantified by polysomnogram: This tool has become one of the most widely used objective metrics in the Robin sequence population. Therefore indications for surgery, timing of palatoplasty and long-term assessment of airway function should be performed in conjunction with sleep study analysis. The effects of mandibular lengthening on feeding difficulty in Robin sequence patient remains a topic of controversy. Studies have demonstrated conflicting results: This can be an area of future study. Agreed-upon indications for surgery and definitive protocols of care have yet to be formulized; future research should focus on achieving these goals. Such studies would require agreed-upon terminology for Robin sequence, an increase in comparative and prospective analysis, and the use of quantifiable metrics of clinical results.
| S-EPMC4219917 | biostudies-other
Project description:Background: Interfragmentary movements have benefits in the improvement of bone formation during distraction osteogenesis (DO). Although several clinical studies reported positive outcomes regarding the application of the cyclic distraction-compression (CDC) dynamization technique in cases with poor bone formation during DO, they are mostly anecdotal without a detailed description. The purpose of this study was to investigate the effectiveness and potential mechanism of different amplitudes and rates of the CDC technique on bone regeneration in a rat femur DO model. Methods: A total of 60 adult male Sprague-Dawley rats underwent right femoral mid-diaphysis transverse osteotomy and were randomly and evenly divided into Control (no manipulation), Group1 (CDC therapy), Group2 (CDC therapy with larger amplitude), and Group3 (CDC therapy with a slower rate) after distraction. The CDC technique was performed during the middle phase of the consolidation period according to different protocols. Animals were sacrificed after 4 and 6 weeks of consolidation. The process of bone formation was monitored by digital radiographs, and the regenerate bone was evaluated by micro-computed tomography (micro-CT), biomechanical test, and histological analysis. The serum contents of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay (ELISA). Results: Bone regeneration after the CDC technique was improved significantly during DO. The digital radiograph, micro-CT, histomorphological analysis, and biomechanical evaluation showed better effects regarding volume, continuity, and mechanical properties of the regenerate bone in Group2 and Group3 when compared to Group1. The angiogenic and osteogenic markers were more highly expressed in Group2 and Group3 than in Group1 according to the immunohistochemical analysis. As for ELISA, the serum contents of HIF-1α and VEGF were also increased after the CDC technique, especially in Group2 and Group3. Conclusion: The CDC dynamization technique has benefits on the improvement of bone formation during DO, and the mechanism may be due to tissue hypoxia activating the HIF pathway followed by the augmentation of osteogenic-angiogenic coupling. Better outcomes may be achieved by moderately increasing the amplitude and slowing down the rate of the CDC technique.
| S-EPMC8806138 | biostudies-literature
Project description:In the field of orthopedic surgery, distraction osteogenesis (DO) is well known for limb lengthening procedures or secondary corrective surgery in the fracture treatment of the extremities. The principle of gradual expansion of bone and surrounding soft tissues as originally described by G.A. Ilizarov is also applicable to the craniofacial skeleton when growth deficiency is present, and the patients affected by craniofacial or dentofacial anomalies may require distraction procedures. The surgical management is comparable. After osteotomy and the mounting of a specific craniomaxillofacial distraction device, active distraction is started after a latency phase of several days, with a distraction rate of up to 1 mm/day until the desired amount of distraction has been achieved. Subsequently, distractors are locked to provide appropriate stability within the distraction zone for callus mineralization during the consolidation phase of 3-6 months, which is followed by a further remodeling of the bony regenerate. After 14 years of clinical application, the role and significance of craniomaxillofacial DO are discussed after reviewing the files of all patients who were treated by craniomaxillofacial distraction procedures.
| S-EPMC6753988 | biostudies-literature
Project description:INTRODUCTION:The aim of this research was to evaluate the level of satisfaction of patients who were undergoing distraction osteogenesis of mandible with extraoral distraction appliance. MATERIAL AND METHODS:The prospective study was performed on 13 patients with facio-mandibular deformity reporting to the Oral Health Sciences Center, PGIMER, Chandigarh, India, who required surgical and orthodontic intervention for correction. A standardized multiple choice questionnaire was provided to all patients at 3 stages of treatment i.e. during predistraction, distraction and post distraction period. RESULTS:Predistraction evaluation showed that the main reason for patients to seek treatment was lack of facial esthetics and all of them were sure that there would be a change in their lives after they underwent this treatment procedure. During distraction phase the most common complaint was pain. None of the patients felt that they were suffering during active distraction phase and all felt that they made the right decision. In post distraction phase, all patients were satisfied with the treatment and felt that the treatment was worth it. Twelve out of 13 patients would recommend treatment to others without any hesitation. CONCLUSION:Our study concludes that distraction osteogenesis of the mandible with extra-oral appliances is acceptable to patients, and improved facial appearance is a positive influence. The appliance and results of the procedure are socially accepted and appreciated.
| S-EPMC4444682 | biostudies-literature
Project description:BackgroundOsteogenesis is tightly coupled with angiogenesis during bone repair and regeneration. However, the underlying mechanisms linking these processes remain largely undefined. The present study aimed to test the hypothesis that epidermal growth factor-like domain-containing protein 6 (EGFL6), an angiogenic factor, also functions in bone marrow mesenchymal stem cells (BMSCs), playing a key role in the interaction between osteogenesis and angiogenesis.MethodsWe evaluated how EGFL6 affects angiogenic activity of human umbilical cord vein endothelial cells (HUVECs) via proliferation, transwell migration, wound healing, and tube-formation assays. Alkaline phosphatase (ALP) and Alizarin Red S (AR-S) were used to assay the osteogenic potential of BMSCs. qRT-PCR, western blotting, and immunocytochemistry were used to evaluate angio- and osteo-specific markers and pathway-related genes and proteins. In order to determine how EGFL6 affects angiogenesis and osteogenesis in vivo, EGFL6 was injected into fracture gaps in a rat tibia distraction osteogenesis (DO) model. Radiography, histology, and histomorphometry were used to quantitatively evaluate angiogenesis and osteogenesis.ResultsEGFL6 stimulated both angiogenesis and osteogenic differentiation through Wnt/β-catenin signaling in vitro. Administration of EGFL6 in the rat DO model promoted CD31hiEMCNhi type H-positive capillary formation associated with enhanced bone formation. Type H vessels were the referred subtype involved during DO stimulated by EGFL6.ConclusionEGFL6 enhanced the osteogenic differentiation potential of BMSCs and accelerated bone regeneration by stimulating angiogenesis. Thus, increasing EGFL6 secretion appeared to underpin the therapeutic benefit by promoting angiogenesis-coupled bone formation. These results imply that boosting local concentrations of EGFL6 may represent a new strategy for the treatment of compromised fracture healing and bone defect restoration.
| S-EPMC8296592 | biostudies-literature
Project description:During development and tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. A thorough understanding of how stem cells in the skeleton interpret mechanical stimuli and enact regeneration will also shed light on how mechanical forces are transduced in other embryonic and regenerative processes. Here we employ a rigorous mandibular distraction model in mice that is genetically dissectable, allowing for detailed examination of the fundamental principles regulating de novo bone formation. Using lineage tracing, we show that regions of new bone are clonally derived, indicating a stem/progenitor cell origin in regeneration. We go on to profile the distraction-specific response of skeletal stem cells (d-SSC) within the facial skeleton and track their downstream progenitors, revealing that this lineage gives rise to the regenerate. Using the assay for transposase accessible chromatin (ATAC-seq), we show that these stem cell populations have a distinct pattern of chromatin accessibility during distraction, including within the FAK pathway. Inhibiting the FAK pathway blocks bone formation and reverts the chromatin accessibility profile back to that of a fractured bone with suboptimal healing. Mechanotransduction and FAK-responsiveness in skeletal stem cells activates regulatory elements and retrotransposons normally active only in primitive neural crest cells; this reversion of chromatin state may allow robust developmental tissue growth that facilitates regeneration.
2018-10-02 | GSE104473 | GEO
Project description:The rapid growth of the brain in the first few years of life drives the expansion of the cranial vault. This expansion occurs primarily at the cranial sutures; premature fusion of these results in growth restriction perpendicular to the axis of the suture. The result of this is physical deformation of the cranial and facial skeleton, as well as the distortion of the underling brain and its physiology. These patients can present with symptoms of raised intracranial pressure, neurodevelopmental delay, as well as the morphological features of craniosynostosis. Acquired conditions such as the slit ventricle syndrome may also result in cephalocranial disproportion with these clinical features. Traditional vault remodeling surgery is able to correct the physical abnormalities as well as correcting cephalocranial disproportion. Its limitations include the degree of scalp expansion achievable as well as resulting defects in the bone. The use of distraction osteogenesis of the cranial vault permits a controlled expansion in a predetermined vector in a gradual manner. When used in the calvarium, this combines the benefits of tissue expansion on the scalp, as well as stimulating the production of new bone, reducing the defects resulting from expansion. In this review, the authors describe some of the surgical considerations important to the use of this technique. This includes the relevant anatomy and technical aspects illustrated with the use of clinical cases. Finally, they present a summary of their experience and discuss the complications associated with cranial vault distraction osteogenesis.
| S-EPMC4219914 | biostudies-other
Project description:Treatment of maxillary hypoplasia has traditionally involved conventional Le Fort I osteotomies and advancement. Advancements of greater than 10 mm risk significant relapse. This risk is greater in the cleft lip and palate population, whose anatomy and soft tissue scarring from prior procedures contributes to instability of conventional maxillary advancement. Le Fort I advancement with distraction osteogenesis has emerged as viable, stable treatment modality correction of severe maxillary hypoplasia in cleft, syndromic, and noncleft patients. In this article, the authors provide a review of current data and recommendations concerning Le Fort I advancement with distraction osteogenesis. In addition, they outline their technique for treating severe maxillary hypoplasia with distraction osteogenesis using internal devices.
| S-EPMC4219915 | biostudies-other