Process Of Distraction Osteogenesis Research Articles

Distraction osteogenesis in combined sequential use of external fixation and nailing (lengthening and then nailing): An experimental study in rabbits.

Limb lengthening relies on the process of distraction osteogenesis. The active periosteal bone formation has been detected in clinical practice with a lengthening and then nail (LATN) technique but has not been confirmed by experimental studies to date. The aim of this study is to compare the tissue regeneration of the distraction regenerate during tibial lengthening in rabbits using a LATN technique. This study was performed on 54 mature rabbits of the Soviet Chinchilla breed, which were divided into three groups of 18 animals. In group 1 (control), the tibia was lengthened in an external fixator. In group 2, the LATN technique was modeled and in group 3, lengthening over nail (LON) was modeled. The total duration of the experiment was 45 days. On the 10th, 15th, 20th, 30th, and 45th day X-ray, computed tomography and morphological studies were performed. In the experimental groups (2 and 3), a more pronounced periosteal bone formation in the area of regenerate was noted when compared to group 1. In group 2 (LATN), wide cortical plates were formed from the intermediate and periosteal areas. In this group, the maximum densitometric density values were noted. Endosteal bone formation was preserved in all groups. The LON and LATN techniques, when compared with the classical Ilizarov lengthening, do not demonstrate any deficiency in the tissue regeneration of the bone tissue at the regenerate sites. The most powerful bone structures are formed with the sequential use of the external fixation and nailing (LATN).

Time-Dependent Collagen Fibered Structure in the Early Distraction Callus: Imaging Characterization and Mathematical Modeling

Collagen is a ubiquitous protein present in regenerating bone tissues that experiences multiple biological phenomena during distraction osteogenesis until the deposition of phosphate crystals. This work combines fluorescence techniques and mathematical modeling to shed light on the mechano-structural processes behind the maturation and accommodation-to-mineralization of the callus tissue. Ovine metatarsal bone calluses were analyzed through confocal images at different stages of the early distraction osteogenesis process, quantifying the fiber orientation distribution and mean intensity as fiber density measure. Likewise, a mathematical model based on the experimental data was defined to micromechanically characterize the apparent stiffening of the tissue within the distracted callus. A reorganization of the fibers around the distraction axis and increased fiber density were found as the bone fragments were gradually separated. Given the degree of significance between the mathematical model and previous in vivo data, reorganization, densification, and bundle maturation phenomena seem to explain the apparent mechanical maturation observed in the tissue theoretically.

Quality of life of children during distraction osteogenesis: a comparison between intramedullary magnetic lengthening nails and external fixators

BackgroundDistraction osteogenesis is a very demanding process. For decades, external fixation was the only reliable option for gradual deformity correction. Recently, intramedullary magnetic nails have gained popularity. This research aimed to assess the quality of life in children during gradual deformity correction using intramedullary lengthening nails compared to external fixation.MethodProspective analysis included children who had gradual lower limb deformity correction between 2017 and 2019. Group A included children who had magnetic lengthening nails; patients in group B had external fixation devices. Child health utility 9D (CHU- 9D) and EuroQol 5D youth (EQ- 5D-Y) were used to measure the quality of life at fixed points during the distraction osteogenesis process. The results were used to calculate the utility at each milestone and the overall quality of life adjusted years (QALYs).ResultsThirty-four children were recruited, group A had 16 patients, whilst group B had 18 patients. The average ages were 16.0 years and 14.7 years for groups A and B, respectively. Group A patients reported significantly better utility compared to group B. This was observed during all stages of treatment (P = 0.00016). QALYs were better for group A (0.44) compared to group B (0.34) (P < 0.0001).ConclusionThe quality of life was generally better in group A compared to group B. In most patients, the health utility progressively improved throughout treatment. In the same way, QALYs were better with the lengthening nails compared to external fixators. The magnetic lengthening devices (PRECICE nails) which were used in this research were recently relabelled to restrict their applications in children; this study was conducted before these restrictions.

Effect of platelet-rich plasma on bone regenerate consolidation in distraction osteogenesis: An experimental study in rabbits.

The aim of this study was to determine the effect of platelet-rich plasma (PRP) on bone regenerate consolidation in a rabbit model of distraction osteogenesis. In this study, 12 male New Zealand rabbits weighing 1600 to 2000 g were used. All the rabbits were randomly divided into two groups (n = 6 per group): PRP group and control group. A two-ring, circular external fixator was applied to the right tibia of each rabbit in both groups. After corticotomy, all the tibiae were distracted at a rate of 0.5 mm/day for 20 days. PRP was injected to the osteotomy sites on the 7th, 14th, and 21st days postoperatively. Mineral density of the new bone tissue formed in the distraction zone was measured using quantitative computed tomography in the 3rd, 4th, and 5th weeks. At the end of the 6th week, the animals were sacrificed, and the specimens were evaluated biomechanically and histologically. Microcomputed tomography assessment showed significant bone mineral density increase from the 3rd to the 6th week (62.3% and 43.7% for the PRP and control groups, respectively). In the PRP group, the measurements on the 3rd, 4th, and 5th weeks were 416 ± 29, 487 ± 9.9, and 675 ± 37.8 HU (Hounsfield units), respectively, whereas in the control group were 313, 374, and 450 HU, respectively. In the comparison of weekly measurements of the two groups, the increase in bone density in the PRP group was higher than that in the control group (P < 0.001). During the mechanical tests, in the PRP group, the mean torsion was 46.50°and the mean torque 0.53 Nm, while in the control group, the mean torsion was 19.33°and the mean torque 0.65 Nm. The mechanical analysis of the groups revealed significant differences in the mean maximum torsion angles (P = 0.024). The histological examination showed that both groups had external and internal periosteal calli. Callus tissue in four rabbits in the PRP group and two rabbits in the control group was remodeled; normal bone formation occurred and distracted bone ends were completely healed. The results of the present study have indicated that PRP injection can enhance bone regenerate consolidation and increase bone mineral density during the healing process of distraction osteogenesis.

Suture Cells in a Mechanical Stretching Niche: Critical Contributors to Trans-sutural Distraction Osteogenesis.

Trans-sutural distraction osteogenesis has been proposed as an alternative technique of craniofacial remodelling surgery for craniosynostosis correction. Many studies have defined the contribution of a series of biological events to distraction osteogenesis, such as changes in gene expression, changes in suture cell behaviour and changes in suture collagen fibre characteristics. However, few studies have elucidated the systematic molecular and cellular mechanisms of trans-sutural distraction osteogenesis, and no study has highlighted the contribution of cell-cell or cell-matrix interactions with respect to the whole expansion process to date. Therefore, it is difficult to translate largely primary mechanistic insights into clinical applications and optimize the clinical outcome of trans-sutural distraction osteogenesis. In this review, we carefully summarize in detail the literature related to the effects of mechanical stretching on osteoblasts, endothelial cells, fibroblasts, immune cells (macrophages and T cells), mesenchymal stem cells and collagen fibres in sutures during the distraction osteogenesis process. We also briefly review the contribution of cell-cell or cell-matrix interactions to bone regeneration at the osteogenic suture frontfrom a comprehensive viewpoint.

Distraction Osteogenesis: Mandible and Maxilla.

Mandibular and maxillary deformities commonly require surgical intervention. Prior to distraction osteogenesis, traditional modalities involving single-staged translocation and rigid fixation were used to correct these craniofacial anomalies. Distraction osteogenesis has evolved as a compelling alternative for treating aesthetic and functional dentofacial defects. The process of distraction osteogenesis involves three phases-latency, activation, and consolidation-which allow for appropriate translation of the affected craniofacial skeleton. This review will cover the role of distraction for managing congenital and acquired deformities of the mandible and maxilla. This novel technique can be performed at numerous anatomical sites along the craniofacial skeleton to treat a variety of anomalies, which serves as a testament to its adaptability and efficacy. Importantly, distraction osteogenesis also has the ability to simultaneously increase bone length and the overlying soft tissue envelope. This advantage results in larger advancements with reduced relapse rates and improved patient satisfaction. While complications remain a concern, it stands to reason that the measurable benefits observed underscore the power and versatility of distraction osteogenesis.

Expert consensus on the treatment of diabetic foot ulcers using tibial transverse transport (2020)

Ilizarov first reported the tibial transverse transport (TTT) for limb regeneration and functional reconstruction. The law of tension-stress could activate and enhance the regenerative potentials of living tissues, leading to growth or regeneration of muscles, fascia, blood vessels, and nerves simultaneously. Ilizarov discovered the phenomenon of rich vascular network formation during distraction osteogenesis process, but he did not apply this technique purposely to reconstruct microcirculation. Chinese orthopedic surgeons first used the TTT to treat lower extremity vascular lesions and diabetic foot ulcers. At present, some small sample clinical studies showed that the TTT could reconstruct microvascular network in the lower limbs of diabetic foot and promote the healing of foot ulcers. The use of TTT could significantly reduce the overall risk of diabetic foot complication especially the amputation risk. This expert consensus is initiated by the Chinese Association of Orthopaedic Surgeons (CAOS), Taskforce Group of Tibial Cortex Transverse Transport Technique for the Treatment of Diabetic Foot Ulcers. This expert consensus provides clear recommendations for indications, contraindications, principles for surgical procedures, preoperative and postoperative management, which maximize the success rate for TTT surgery in treatment of severe diabetic foot ulcers.

Overexpressed osteoactivin reduced osteoclastic callus resorption during distraction osteogenesis in mice.

Distraction osteogenesis is a widely used surgical technique to treat bone deformity and shortening. Several biological treatments have been studied to enhance bone formation during distraction osteogenesis in animals. However, role of osteoactivin in the osseous tissues during distraction osteogenesis remains poorly understood. In this animal experimental study, we investigated the spatiotemporal expression of osteoactivin by immunohistochemistry and real-time PCR using a mouse model for tibial lengthening. Furthermore, to address the role of osteoactivin in bone lengthening, we subjected the osteoactivin-transgenic mice to distraction osteogenesis model. During the lag phase, the fibroblast-like cells (possible progenitors of the osteoblasts or chondrocytes), which mainly express osteoactivin, were infiltrated into the osteotomy site. Osteoactivin was ubiquitously expressed in the lengthened segment during the distraction and consolidation phases. Consistent with the immunohistochemical analysis, the levels of the osteoactivin transcripts in the tibias were significantly increased throughout the distraction osteogenesis process. The bone mineral content in the osteoactivin-transgenic mice calculated using peripheral quantitative computed tomography was also significantly increased at the remodeling zone. The histomorphometric analysis revealed that newly formed callus resorption in the remodeling zone was significantly reduced but bone formation was not altered in the osteoactivin-transgenic mice. We conclude that osteoactivin functions as an inhibitor of callus resorption during the consolidation phase of distraction osteogenesis.

Enhancement of bone regeneration with the accordion technique via HIF-1α/VEGF activation in a rat distraction osteogenesis model.

Axial micromotion of bone fragments promotes callus formation and bone healing during the process of distraction osteogenesis (DO). This study investigated the effects of the combined axial compression and distraction (accordion) technique on bone regeneration in rat DO model. Male Sprague-Dawley rats (n=62) underwent right tibial transverse osteotomy and were randomly divided into four groups after lengthening: control (no manipulation) and three experimental groups assigned on the basis of the period of accordion manoeuvres in the consolidation phase (Groups 1, 2, and 3 with accordion technique applied at Weeks 1, 3, and 5, respectively). Animals were terminated at 1week after each accordion phase (i.e., Weeks 2, 4, and 6). Callus formation was monitored by X-ray radiography; new bone quality was evaluated by microcomputed tomography, histological analysis, and mechanical testing. Serum levels of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were measured. Callus formation after accordion manoeuvre at Week 3 (Group 2) increased significantly over time of consolidation. The microcomputed tomography and mechanical analysis revealed Group 2 had more newly formed bone and superior mechanical properties in contrast to the other groups at termination. Histomorphological and immunohistochemical analyses confirmed a greater degree of osteogenesis and angiogenesis corresponding to increased serum levels of HIF-1α and VEGF in Group 2. The accordion technique was effective in promoting bone consolidation via activation of HIF-1α/VEGF during DO. The accordion technique may be used in the middle phase of bone consolidation to promote bone formation in patients undergoing DO treatment.

PARACRINE REGULATORS IN DISTRACTION OSTEOGENESIS (pilot study)

Purpose – to evaluate effect of protein extracted from lengthened skeletal muscles on callus formation in dogs after tibia lengthening using Ilizarov method.Materials and methods. The authors studied properties of distraction callus formation in three groups of dogs after tibia lengthening by Ilizarov method. In the first group (n = 10) distraction was achieved at a rate of 1 mm in four stages during 28 days. In the second (n = 4) and third (n = 4) groups distraction was done at a rate of 1.5 mm in 6 stages per day within 20 days. Mean lengthening value in all groups amounted to 14,64±0,67% of the overall segment length. At the 10th day of distraction the authors introduced to animals of the second group into anterior tibial and gastrocnemius muscles of the lengthened segment at callus level the extract of sarcoplasmic proteins in amount of 1.5ml based on 1 mg of lyophilizate per 1 kg of body weight (protein concentration in injectate amounted to 30±2 gr/l). Animals in the third group received natural saline solution in the same manner. Extract consisted of lyophilized sarcoplasmic proteins harvested from anterior tibial muscle of animal at 14th day of lengthening by Ilizarov method (rate of 1 mm per day in 4 stages). Extraction was performed according to patented method (Russian Federation patent for invention №2476234) by consecutive muscle proteins sedimentation in KCl solutions of varied ionic strength. The lyophilizate was sterilized after obtaining and dissolved in normal saline solution prior to introduction.Results. Radiographic signs of anatomically solid callus in the first group were observed in the average at 33±1 day of fixation; in the second group – at 24±2 day; in the third group – at 39±3. Difference in mean values of fixation in animals of second group as compared to first and third groups was significant (р = 0,04). After extract introduction the animals of the second group demonstrated a greater growth of γ-globulins and α2-globulins fraction volumes.Conclusion. Skeletal muscles of limb segment lengthened by Ilizarov method produce specific factors that impact the process of distraction osteogenesis.

Troubleshooting Distraction Osteogenesis for Craniosynostosis

Purpose: We previously reported that distraction osteogenesis is less invasive and gives greater skull advancement compared to conventional cranioplasty [Akai et al: Pediatr Neurosurg 2006;42:288-292]. In this study, we analyzed the distraction osteogenesis process and tried to identify and solve various technical problems. Patients and Results: We operated on 22 patients, 5 syndromic and 17 nonsyndromic. During treatment, we encountered several problems: (i) dural laceration during craniotomy (2 cases), solution: repair by suturing with fascia; (ii) skull fracture at sphenofrontal or coronal sutures (2 cases), solution: completed distraction; (iii) device dislocation during distraction (1 case), solution: the device was secured to the skull with stainless wire; (iv) wound issues around shaft and device (3 cases), solution: treated with antibiotic ointment. Discussion: (1) Extra caution is needed to avoid dural damage at frontal bottom burr holes. (2) Completion of craniotomy should be confirmed by checking if the bone flap moves in sync with brain pulsation. The craniotomy line should be placed forward of coronal sutures. (3) For patients younger than 2 years, employ clamp-type devices. (4) Shafts should be cut short enough to prevent their tips from exerting pressure or puncturing the scalp from beneath. Conclusions: The distraction osteogenesis technique has complications that may not occur in conventional one-stage cranioplasty. In this study, neither age at operation nor distraction distance were significant causes of complications during distraction osteogenesis.

Orientação do plano mandibular após distração osteogénica dento-suportada: estudo experimental no cão

ObjectivesSeveral studies suggest that the orientation of the distractors is one of the most important biomechanical parameters in the success of mandibular distraction osteogenesis. The purpose of this study is to evaluate the angle of the mandible body before and after the process of distraction osteogenesis in an animal model. MethodsTen one year old male dogs, weighting 15-18 Kg, were used for this experiment. Three remained as a control group and seven underwent of bilateral mandibular lengthening by intraoral distraction osteogenesis. Lateral cephalometric radiographs were taken of each animal's head before the beginning of distraction and after the consolidation period. Cephalometric analyses were performed by direct digital method. It was created a cephalometric angular variable (Cd-Aa-Ii (°)) and a cephalometric plane (Cd-Aa) for orientation and reference, not changeable by the experimentation and thus allowing to measure the angle of the anterior part of the mandibular body and ramus, before and after mandibular lengthening. ResultsThere were statistically significant differences from the linear variable between the different groups. The mean lengthening, measured in radiographic cephalometry, was 8.7mm. There were no statistically significant differences in the variable angle between the control group and the group protocol. ConclusionsThe distractors anchored on the teeth and parallel to the occlusal plane; significantly increase the anterior bone segment without producing lateral changes or vertical statistically significant changes.

Efeitos do ritmo da distração osteogénica no alongamento sagital mandibular

ObjectiveFrequency of activation during distraction can theoretically influence the process of distraction osteogenesis. The aim of the study is to evaluate the effect of two different frequencies of distraction in the amount and architecture of new bone using a tooth-borne distractor. Materials and methodsTen beagle dogs, weighing between 15-18kg, were used. Three remained as the control group and seven underwent a mandibular distraction protocol. Both hemi-mandibles were used for experimental purposes, with the following division: Group A: Six did not undergo any surgical procedure, remaining as a control group; Group B: Seven were subjected to two daily activations of 0.5mm, with an interval of twelve hours; Group C: Seven received a single daily distraction of 1mm.After the distraction period, all devices were properly blocked and submitted to a consolidation period of 12 weeks. The mean distraction achieved was 9,8mm.The evaluation of bone tissue was made radiographically and by Dual X-ray absorptiometry, and the values obtained were subsequently sent for statistical analysis. ResultsRadiographic evaluation showed that a greater the consolidation period leads to a greater amount of bone tissue in the distraction gap. There were no statistically significant differences in bone mineral content and bone mineral density among groups A, B and C. There were statistically significant differences between the coefficient of variation in groups B and C (p=0,041). ConclusionsAn increased in rhythm from one to two daily activations changed the quality of new bone present in the area created by distraction.

The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible

The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague–Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.

Alveolar Distraction Osteogenesis: Revive and Restore the Native Bone

In prosthodontics, knife-edge bony alveolar ridges can cause a problem in their rehabilitation. The distraction osteogenesis process raises the medullary component of the alveolus, allowing the labial plate of the existing natural bone to be displaced. This process involves mobilization, transport, and fixation of a healthy segment of bone adjacent to the deficient site. It entails use of the gradual controlled displacement of surgically created fractures, which results in simultaneous expansion of soft tissue and bone volume. A mechanical device, the alveolar distraction device, is used for this purpose. This modality of treatment can be used in implant dentistry cases for rehabilitation of resorbed ridges. The objective of this overview is to explain this procedure wherein the alveolar housing, including the osseous and soft-tissue components, is enlarged in a single, simultaneous process, which makes creation of an appropriate alveolar morphology possible.

Growth mixture model of distraction osteogenesis: effect of pre-traction stresses

In tensional studies of bone fragments during limb lengthening, it is usually assumed that the stress level in the gap tissue before each distraction step (pre-traction stress) is rather modest. However, during the process of distraction osteogenesis, a large interfragmentary gap is generated and these pre-traction stresses may be important. To date, to the authors' knowledge, no computational study has been developed to assess the effect of stress accumulation during limb lengthening. In this work, we present a macroscopic growth mixture formulation to investigate the influence of pre-traction stresses on the outcome of this clinical procedure. In particular, the model is applied to the simulation of the regeneration of tibial defects by means of distraction osteogenesis. The evolution of pre-traction forces, post-traction forces and peak forces is evaluated and compared with experimental data. The results show that the inclusion of pre-traction stresses in the model affects the evolution of the regeneration process and the corresponding reaction forces.

An immunohistochemical analysis of the temporal and spatial expression of growth factors FGF 1, 2 and 18, IGF 1 and 2, and TGFbeta1 during distraction osteogenesis.

Distraction osteogenesis (DO) is a well established surgical technique that generates new bone by gradual distraction of two bony segments. In this study, we investigated the temporal and spatial profile of FGF 1, 2 and 18, IGF 1 and 2, and TGFbeta1 during distraction osteogenesis using immunohistochemistry. An osteotomy was performed on the right tibia of 13 white male New Zealand rabbits. After a delay of 7 days, distraction was started at a rate of 0.25 mm/12 hrs for 3 weeks which was followed by a 3 week period of consolidation. Immunohistochemical analysis was performed on a weekly interval to determine the expression of the growth factors. Staining of all growth factors was apparent at various levels in the centre and callus region in fibroblasts and chondrocyte cells. FGF2 however, showed continued high expression in osteoblasts. Within two weeks after the end of distraction all growth factors showed a reduction in expression except for FGF18 which maintained high levels of expression (up to 100% staining) throughout the distraction and consolidation phases. The study suggests that in comparison to the other investigated growth factors, FGF18 may play in important role throughout the entire process of distraction osteogenesis.

The healing potential of the periosteum: Molecular aspects

The presence of pluripotential mesenchymal cells in the under surface of the periosteum in combination with growth factors regularly produced or released after injury, provide this unique tissue with an important role in the healing of bone and cartilage. The periosteum contributes in the secondary callus formation with cells and growth factors and should always be preserved and protected when surgery is performed for the management of a fracture. The current evidence about the cellular interactions, the stimulants and the signalling pathways related to osteogenesis and chondrogenesis is described. An essential knowledge of the basics related to the contribution of the periosteum in the healing of fractures, osteotomies, during the process of distraction osteogenesis and in some degree in the repair of cartilagenous defects, provides the surgeons with a better insight to understand the upcoming "biological" interventions in the management of skeletal injuries.

Discussion

Since its first clinical introduction by McCarthy, the application of craniofacial distraction osteogenesis has exploded over the past decade. 1 Craniofacial Distraction Osteogenesis. , Mosby, St Louis, MO2001 Google Scholar A number of experimental and clinical investigations have shown that gradual mechanical traction of bone segments at an osteotomy site created in the craniofacial region generates new bone parallel to the direction of traction and allows adaptation of the surrounding soft tissues to new dimensions with complete preservation of function and without relapse. Moreover, soft tissue elongation is one of the most important parts of the distraction osteogenesis process, significantly affecting the result of lengthening.

A submerged osteodistraction device: an innovative technique for experimental animal studies.

The author presents a submerged mandibular distraction device that can be used in the rabbit mandible for additional experimental studies of the distraction osteogenesis process. A distractor to suit the rabbit mandible was designed by the author. It is fixed to the mandible under layers of skin and mucoperiosteum. It can distract both sides of the mandible simultaneously without the need for two separate devices. The body of the distractor is 1.5 x 1.0 cm, and the total length is 3 cm. It weighs 2 g.