Consolidation In Distraction Osteogenesis Research Articles

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.

Overview of methods for enhancing bone regeneration in distraction osteogenesis: Potential roles of biometals.

BackgroundDistraction osteogenesis (DO) is a functional tissue engineering approach that applies gradual mechanical traction on the bone tissues after osteotomy to stimulate bone regeneration. However, DO still has disadvantages that limit its clinical use, including long treatment durationMethodsReview the current methods of promoting bone formation and consolidation in DO with particular interest on biometal.ResultsNumerous approaches, including physical therapy, gene therapy, growth factor-based therapy, stem-cell-based therapy, and improved distraction devices, have been explored to reduce the DO treatment duration with some success. Nevertheless, no approach to date is widely accepted in clinical practice due to various reasons, such as high expense, short biologic half-life, and lack of effective delivery methods. Biometals, including calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), manganese (Mn), and cobalt (Co) have attracted attention in bone regeneration attributed to their biodegradability and bioactive components released during in vivo degradation.ConclusionThis review summarizes the current therapies accelerating bone formation in DO and the beneficial role of biometals in bone regeneration, particularly focusing on the use of biometal Mg and its alloy in promoting bone formation in DO. Translational potential: The potential clinical applications using Mg-based devices to accelerate DO are promising. Mg stimulates expression of multiple intrinsic biological factors and the development of Mg as an implantable component in DO may be used to argument bone formation and consolidation in DO.

High-purity magnesium pin enhances bone consolidation in distraction osteogenesis via regulating Ptch protein activating Hedgehog-alternative Wnt signaling

Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. Magnesium has been proven to promote distraction osteogenesis. However, its mechanism of promoting distraction osteogenesis is not thoroughly studied. In this work, a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis. Mechanical test, radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time. Further RNA sequencing investigation found that alternative Wnt signaling was activated. In further bioinformatics analysis, it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway. We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein. In conclusion, HP Mg implants have the potential to enhance bone consolidation in the DO application, and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.

The effects of tubular structure on biomaterial aided bone regeneration in distraction osteogenesis

Long duration of bone consolidation in distraction osteogenesis (DO) has been regarded as a major disadvantage. Porous bone substitutes have been long used in aiding bone formation. However the effects of geometric tubular structure of the porous scaffolds on bone formation in DO remains unknown. This study investigated the effects of porous scaffolds with three different geometric structures on bone regeneration in a rabbit DO model. β-tricalcium phosphate (β-TCP) was fabricated into no tubular, single tubular, or multi-tubular structure constructs. The microstructure of the three types of β-TCP constructs was determined by scanning electron microscope (SEM). Unilateral tibial osteotomy was made at the midshaft with 1 cm tibial shaft removed, fixed with an external lengthener in adulkt New Zealand white rabbits. After acute tibial shortening of 0.5 cm, the remaining 0.5 cm defect was implanted with β-TCP constructs with no tubular, single tubular, or multi-tubular structure. Five days after surgery, the tibia was lengthened at 0.5 mm/12 h for 5 days. After further 28 days of consolidation, the animals were terminated. Bilateral tibial specimens were collected for X-ray, micro-computed tomography examination, four-point bending mechanical test and histological analysis. SEM results showed that pore sizes and pore interconnectivity in all three types of β-TCP constructs were identical. 38 days after surgery (4 weeks after lengthening), the new bone formation and mechanical properties were significantly enhanced in the groups implanted with multi-tubular and single tubular constructs, comparing to the group implanted with no tubular constructs. Furthermore, the group implanted with multi-tubular constructs had significantly better mechanical properties comparing to the group implanted with single tubular constructs. Histological results confirmed that group implanted with multi-tubular constructs had the most advanced bone formation and remodelling in the defect gap. The current study confirmed that β-TCP constructs with multi-tubular structure was the best choice as scaffold aid for bone regeneration in DO, indicating a novel fabrication approach of multi-tubular constructs for rapid bone formation together with DO procedure. Porous β-TCP scaffold with a multi-tubular structure used in combination with DO procedure can significantly shorten the bone consolidation duration. The tubular shaped porous β-TCP scaffold may be used to fill bone defect and to aid bone formation, consolidaiton and remodelling in DO.

Low-intensity pulsed ultrasound enhances callus consolidation in distraction osteogenesis of the tibia by the technique of lengthening over the nail procedure

BackgroundLow-intensity pulsed ultrasound (LIPUS) has been widely accepted in promoting the fracture healing process. However, there have been limited clinical trials focused on the efficacy of LIPUS during distraction osteogenesis (DO) by the technique of lengthening over the nail procedure. The purpose of the current study was to evaluate the efficacy of LIPUS during DO.MethodsWe retrospectively evaluated 30 patients (60 segments) who underwent simultaneous bilateral tibial lengthening over the nail. The patients were grouped into the LIPUS group and the control group based on LIPUS stimulation. The two patient groups were compared for demographic data (sex, age at operation, preoperative height, BMI, and smoking history), qualitative assessments of the callus (callus shape and type), external fixation index, and four cortical healing indexes.ResultsFifteen patients (30 segments) were classified as the LIPUS group, and another 15 patients (30 segments) were classified as the control group. No significant differences were found in the assessed demographic data between the groups. LIPUS stimulated a more cylindrical, more homogenous, and denser type of callus formation at the end of the distraction phase. The two groups exhibited equivalent outcomes in terms of external fixation index (p = 0.579). However, significant differences were found in healing indexes of the anterior and medial cortices (p < 0.001 and p = 0.002, respectively). The healing indexes of those cortices in the LIPUS group (mean of 36.6 days/cm and 32.5 days/cm, respectively) reflected their significantly faster healing compared to the control group (mean HI of 57.5 days/cm and 44.2 days/cm, respectively). There were no LIPUS-related complications.ConclusionsLIPUS is a noninvasive and effective adjuvant therapy to enhance callus maturation during DO. It enhances callus consolidation and may have a positive effect on the appropriate callus shape and type.

Porcine brain extract promotes osteogenic differentiation of bone marrow derived mesenchymal stem cells and bone consolidation in a rat distraction osteogenesis model

Distraction osteogenesis (DO) is the gold standard to treat large bone defects, but long consolidation period is a major limitation. Innovative efforts to promote osteogenesis are needed. Porcine brain extract (PBE) was reported to enhance the proliferation and differentiation of multiple primary cells. In this study, we aimed to develop a method for collecting PBE and investigate its effects on osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs) and bone consolidation in a rat DO model. The PBE was collected from neonatal brain tissues of porcine fetus and was used to treat rBMSCs. Following PBE treatment (700 ng/ml), osteogenic differentiation was assessed. Further, we locally injected PBE (7 μg/ml, 100μl) or PBS (100μl) into the gap in a Sprague-Dawley (SD) male rat DO model every three days till termination. X-rays, micro-computed tomography, mechanical testing, histology and immunohischemistry examinations were used to exam the quality of the regenerates. The alkaline phosphatase, calcium deposits, and steogenic markers in the PBE treated rBMSCs were significantly increased. In the rat model, new bone properties of bone volume/total tissue volume and mechanical strength were higher in the PBE treated group. Histological analysis also confirmed more mineralized bone after PBE treatment. The current study reports a standard protocol for PBE collection and demonstrated its positive effects on osteogenic differentiation and bone consolidation in DO. Since the PBE is readily available and very cost effective, PBE may be a potential new bio-source to promote bone formation in patients undergo DO treatment.

Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis: A contemporary review of experimental studies.

ObjectivesDistraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results.MethodsWe hereby review the published literature on the use of MSCs in promoting bone consolidation during DO.ResultsStudies differed in animal type (mice, rabbit, dog, sheep), bone type (femur, tibia, skull), DO protocols and cell transplantation methods.ConclusionThe majority of studies reported that the transplantation of MSCs enhanced bone consolidation or formation in DO. Many questions relating to animal model, DO protocol and cell transplantation regime remain to be further investigated. Clinical trials are needed to test and confirm these findings from animal studies.Cite this article: Y. Yang, S. Lin, B. Wang, W. Gu, G. Li. Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis: A contemporary review of experimental studies. Bone Joint Res 2017;6:385–390. DOI: 10.1302/2046-3758.66.BJR-2017-0023.

Staphylococcal enterotoxin C2 expedites bone consolidation in distraction osteogenesis.

Distraction osteogenesis (DO) technique could be used to manage large-size bone defect successfully, but DO process usually requires long duration of bone consolidation. Innovative approaches for augmenting bone consolidation are of great need. Staphylococcal enterotoxin C2 (SEC2) has been found to suppress osteoclastogenesis of mesenchymal stem cells in vitro. In this study, we investigated the effect of SEC2 on proliferation and osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). Further, we locally administrated SEC2 (10 ng/ml) or PBS into the distraction gap in Sprague-Dawley male rat DO model every 3 days till termination at 3 and 6 weeks. The regenerates were subjected to X-rays, micro-computed tomography, mechanical testing, histology, and immunohischemistry examinations to assess new bone quality. SEC2 had no effect on cell viability. The calcium deposition was remarkably increased and osteogenic marker genes were significantly up-regulated in rBMSCs treated with SEC2. In rat DO model, SEC2 group had higher bone volume/total tissue volume in the regenerates. At 6 weeks, mechanical properties were significantly higher in SEC2-treated tibiae comparing to the control group. Histological analysis confirmed that the new bone had improved quality in SEC2 treated group, where the osteocalcin and osterix expression in the regenerates was up-regulated, indicating faster bone formation. The current study demonstrated that SEC2 local injection promotes osteogenesis and enhanced bone consolidation in DO. The findings support application of SEC2 as a potential novel strategy to expedite bone consolidation in patients undergoing DO treatment. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1215-1225, 2017.

Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet-Rich Plasma Accelerate Distraction Osteogenesis in A Canine Model.

Distraction osteogenesis (DO) is a surgical procedure used to generate large volumes of new bone for limb lengthening. In this animal experimental study, a 30% lengthening of the left tibia (mean distraction distance: 60.8 mm) was performed in ten adult male dogs by callus distraction after osteotomy and application of an Ilizarov fixator. Distraction was started on postoperative day seven with a distraction rate of 0.5 mm twice per day and carried out at a rate of 1.5 mm per day until the end of the study. Autologous bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich plasma (PRP) as the treatment group (n=5) or PRP alone (control group, n=5) were injected into the distracted callus at the middle and end of the distraction period. At the end of the consolidation period, the dogs were sacrificed after which computerized tomography (CT) and histomorphometric evaluations were performed. Radiographic evaluationsrevealed that the amount and quality of callus formations were significantly higher in the treatment group (P<0.05). As measured by CT scan, the healing parametersin dogs of the treatment group were significantly greater (P<0.05). New bone formation in the treatment group was significantly higher (P<0.05). The present study showed that the transplantation of BM-MSCs positively affects early bony consolidation in DO. The use of MSCs might allow a shortened period of consolidation and therefore permit earlier device removal.

Is DBM beneficial for the enhancement of bony consolidation in distraction osteogenesis? A randomized controlled trial.

The aim of the present study was to compare the radiographic and clinical outcomes of DBM injection and conventional treatment during tibial lengthening over an intramedullary nail in adult patients with short stature. Twenty-nine patients were randomized to receive DBM injection (n = 14) or conventional treatment without any injection (n = 15) and evaluated. The outcome was measured on the basis of the pixel value ratio (PVR) in the digital radiographs during the consolidation period; healing index; clinical assessment; and the rate of complications. In the DBM group, the mean PVR of 1 (mineral density of the callus is comparable to the adjacent bone) was reached by 40 weeks in anterior and medial cortices which was significantly different than that in the control group (P = 0.03 for anterior cortex; P = 0.04 for medial cortex). The average healing index in the DBM group was 39.8 ± 5.3 days/cm compared to 44.3 ± 5.8 days/cm in the control group (P = 0.05). There were no significant differences in clinical outcomes (P = 0.23) and functional status (P = 0.47) including complications (P = 0.72) between two groups. In this randomized clinical trial, injection of DBM at the time of initial operation enhanced consolidation of regenerate callus without interfering with clinical outcomes compared to that with conventional treatment.

Extracorporeal Shock Wave Accelerates Consolidation in Distraction Osteogenesis of the Rat Mandible

One of major limitations of applying distraction osteogenesis for craniofacial skeleton hypoplasia is the long duration for bony consolidation. This study investigated whether extracorporeal shock wave therapy (ESWT) could accelerate bony consolidation in distraction osteogenesis of the rat mandible. An L-shape osteotomy was performed unilaterally in the hemimandible of Sprague-Dawley rats. An internal distracter was employed to create a 7-mm distraction gap in the mandible. One hundred twenty rats were divided into three groups. The distraction zone of the mandible was received no treatment as controls (group I). Group II received ESWT (500 impulses at 14 kV) at 2 weeks postoperatively. Group III treated with 500 ESW impulses at 21 kV at 2 weeks postoperatively. Dual-energy X-ray absorptiometry and material testing showed that optimal dosage of ESWT in group II significantly increased mineral density and enhanced biomechanical strength of the bone tissue. In histomorphological analysis, the mandibular tissue in group II showed intense osteoblastic cell recruitment, new bone formation, and vascularization. The osteoblasts in the distracted zone in group II indicated significantly strong immunoreactivities for proliferating cell nuclear antigen, vascular endothelial growth factor, and bone morphogenetic protein-2, when compared with other groups. Optimal dosage of ESWT was beneficial for accelerating facial skeleton consolidation and bone regeneration in the distracted rat mandible tissue. The mechanism was presumably associated with the up-regulation of neovascularization, cell proliferation, and osteogenic growth factor expression in bone microenvironment.

A novel OP-1 delivery system for the potential acceleration of regenerate formation and consolidation in distraction osteogenesis

A novel OP-1 delivery system for the potential acceleration of regenerate formation and consolidation in distraction osteogenesis

Effect of Calcium Sulfate Pellets on Early Bone Mineralization in Distraction Osteogenesis for Craniofacial Microsomia in Adults

The purpose of this project was to study the effect of calcium sulfate pellets on early bony consolidation in distraction osteogenesis. A total of 13 patients (control group: five patients; calcium sulfate group: eight patients) were operated on between April 2001 and December 2004. The age of the patients ranged from 18 to 25 years. In the calcium sulfate group, after completing a mandibular osteotomy, a total of 4 mm was distracted initially. Nine to 10 calcium sulfate (Osteoset) pellets were implanted into the 4-mm distracted gap of mandible. In the control group, a mandibular osteotomy alone was created without the initial 4-mm distraction gap and the implantation of calcium sulfate. Five days after the operation, the distraction of the mandible was performed at a rate of 1 mm per day. The distracted length of the mandible was between 7 and 23 mm. The follow-up period ranged between 10 and 22 months. In the calcium sulfate group, the percentage of bone mineral density in the distracted area, compared with the normal mandible, was much higher than in the control group with a statistical significance of P < 0.05. The external distraction devices of the calcium sulfate group were removed 5 to 7 weeks after distraction. The devices of the control group were removed by 11 or 12 weeks. In conclusion, results of the present study suggested that calcium sulfate is a very active, economic, and biocompatible osteoconductive material, which has a good effect on early consolidation in distraction osteogenesis.

Stimulation of EP4 receptor enhanced bone consolidation during distraction osteogenesis

The objective of this study was to confirm whether an agonist of prostaglandin E receptor subtype EP4 can enhance bone consolidation in distraction osteogenesis. A rat distraction osteogenesis model was generated. A unilateral external fixator was fixed to the left femur of the rats of this model after osteotomy. Seven days later, 0.25 mm/12 h or 0.5 mm/12 h elongation was performed for 2 weeks. A systemic administration of an EP4 receptor agonist (ONO 4819 . CD, 3, 10, 30 microg/kg) or normal saline by subcutaneous injection was also performed for 2 weeks. The animals were sacrificed 10, 14, 17, 21, and 42 days after the operation. Radiographic examination, histological examination, and measurements of bone mineral density (BMD) and distraction-callus hardness were performed to qualitatively and quantitatively evaluate new bone formation. Twenty-one days after the operation, the experimental group had a higher BMD and a higher distraction-callus hardness than that of the control group. Forty-two days after the operation, BMD was similar among all of the groups. But the hardness of the experimental groups increased more than that of the control group, so the statistical differences in distraction-callus hardness became more distinct between the two groups, indicating an improved remodeling of the distraction callus. These findings are also supported by histological examination. Subcutaneous injection of an EP4 receptor agonist can promote bone formation and remodeling during distraction osteogenesis. ONO 4819 * CD might be a potential candidate for shortening the treatment time of distraction osteogenesis.

The Effect of Chitosan Bead Encapsulating Calcium Sulfate as an Injectable Bone Substitute on Consolidation in the Mandibular Distraction Osteogenesis of a Dog Model

The purpose of this project was to study the effect of chitosan bead encapsulating calcium sulfate, which provides a sustained release of chitosan and calcium sulfate after implantation, on early bony consolidation in distraction osteogenesis of a dog model. Forty-five dogs were used for this study. An external distraction device was applied to the mandibular body after a vertical osteotomy and mandibular distraction was initiated 5 days after the operation at a rate of 1 mm/day up to a 10-mm distraction. The experimental group was divided into a control group (I), hyaluronic acid group (II), chitosan group (III), calcium sulfate group (IV), and chitosan bead encapsulating calcium sulfate group (V). Normal saline was injected in group I. In group II, 1 mL of hyaluronic acid solution was injected into the distracted region. In group III, 1 mL of injectable solution of chitosan mixed with hyaluronic acid was implanted. In group IV, 1 mL of injectable solution of calcium sulfate mixed with hyaluronic acid was implanted. In group V, an injectable form of powdered chitosan bead encapsulating calcium sulfate mixed with 1 mL volume of hyaluronic acid was implanted. Bone mineral density was 12% of the contralateral normal mandible at 3 weeks, 23.4% at 6 weeks in group I, 15% at 3 weeks, 29.1% at 6 weeks in group II, 16% at 3 weeks and 32% at 6 weeks in group III, 30.4% at 3 weeks and 52.8% at 6 weeks in group IV, and 33.6% at 3 weeks and 55% at 6 weeks in group V with statistical significance (P < .005). The mean 3-point failure load was compared with the intact contralateral mandible and noted to be 12% in the control group, 16% in group II, 18% in group III, 34.3% in group IV, and 31.7% in group V. Difference of mean percentages between one group and another was statistically significant (P < .005). In the histologic findings, new bone was generated in all groups. In groups IV and V, the formation of active woven bone was observed throughout the distracted region at 6 weeks. The amount of new bone formation in the distracted zone was in the order of group IV and V, III and II, and the control group. These findings suggest that chitosan bead encapsulating calcium sulfate appears to facilitate early bony consolidation in distraction osteogenesis.

The bone regenerative effect of chitosan microsphere-encapsulated growth hormone on bony consolidation in mandibular distraction osteogenesis in a dog model.

The purpose of this project was to study the effect of chitosan microsphere-encapsulated human growth hormone, which causes sustained release of chitosan and human growth hormone after implantation on early bony consolidation in distraction osteogenesis of a canine model. Forty-eight dogs were used for this study. An external distraction device was applied to the mandibular body after a vertical osteotomy, and the mandibular distraction was started 5 days after the operation at a rate of 1 mm/d up to a 10-mm distraction. The experimental group was divided into a control group (I), hyaluronic acid group (II), chitosan microsphere group (III), and chitosan microsphere-encapsulated human growth hormone group (IV). Normal saline was injected in group I. In group II, a 1-ml volume of hyaluronic acid solution was injected into the distracted area. In the group III, powder of chitosan microspheres and hGH were mixed with a 1-ml volume of hyaluronic acid to make an injectable form, and it was implanted into the distracted area. In group IV, powder of chitosan microsphere-encapsulated hGH was mixed with a 1-ml volume of hyaluronic acid. A total of 1-ml volume of the solution mix was implanted into the distracted area. Five dogs in each group (total of 20 dogs) were killed 3 weeks after completion of distraction. Twenty-eight dogs were killed at 6 weeks. Bone mineral density was 13.1% of the contralateral normal mandible at 3 weeks and 29.6% at 6 weeks in group I, 16.4% at 3 weeks and 40.4% at 6 weeks in group II, 16.6% at 3 weeks and 45.95% at 6 weeks in group III, and 29.6% at 3 weeks and 66.7% at 6 weeks in group IV. The mean three-point failure load was 16.1% in the control group, 34.7% in group II, 41.5% in group III, and 52.1% in group IV compared with the intact contralateral mandible, with statistical significance. In the histological findings, new bone was generated in all groups. In group IV, the formation of active woven bone was observed throughout the distracted area at 6 weeks. The amount of new bone formation in the distracted zone was in the order of group IV, group III, group II, and the control group. In conclusion, these findings suggest that chitosan microsphere-encapsulated hGH seems to be quite effective in early bone consolidation in distraction osteogenesis.

The bone regenerative effect of growth hormone on consolidation in mandibular distraction osteogenesis of a dog model.

The purpose of this project was to study the effect of growth hormone on early bony consolidation in distraction osteogenesis of a dog model. Sixteen dogs were used for this study. The vertical osteotomy on the mandibular body was extended downward. An external distraction device was applied to the mandibular body and the mandibular distraction was started 5 days after the operation at a rate of 1 mm/d up to a 10-mm distraction. The experimental group was divided into a control group and growth hormone group. Dogs in the growth hormone group received a daily subcutaneous injection of 100 microg (1 IU) of recombinant human growth hormone per kilogram of body weight. The daily administration of growth hormone was performed from the day of the osteotomy through the whole distraction period to the sacrifice. Normal saline was injected in the control group. Eight dogs were allocated to each group. Two dogs in each group, a total of four dogs, were killed at 2 weeks after completion of distraction, four dogs were killed at 4 weeks, and the other eight dogs were killed at 6 weeks. The level of serum IGF-I in the growth hormone group was elevated and peaked between 8 days and 12 days after systemic administration of growth hormone. Bone mineral density was higher in the growth hormone group and lower in the control group for the whole period. Bone mechanical strength was 300% higher in the growth hormone group than in the control group. However, results were more suggestive than conclusive. On histological examination, the formation of a substantial amount of active woven bone was observed throughout the distracted zone at six weeks in the growth hormone group. In the control group, new bone was generated from the edge to the center of the distracted zone. In addition, most of the central area of the distracted zone was filled with fibrous tissue at six weeks. In conclusion, these findings suggest that growth hormone appears to be effective in early bony consolidation in distraction osteogenesis.

The role of hyaluronic acid, chitosan, and calcium sulfate and their combined effect on early bony consolidation in distraction osteogenesis of a canine model.

The purpose of this project was to study the effect of hyaluronic acid, calcium sulfate, and chitosan on early bony consolidation in distraction osteogenesis of a canine model. Sixteen dogs were used for this study. The lateral surface of the mandibular body was exposed in the subperiosteal plane, and the vertical osteotomy on the mandibular body was extended downward. An external distraction device was applied to the mandibular body, and the mandibular distraction was started 5 days after the operation at a rate of 1 mm/d up to a 10-mm distraction. The experimental group was then divided into a control group, chitosan group, hyaluronic acid group, calcium sulfate combined with hyaluronic acid group, and calcium sulfate combined with chitosan group, depending on the type of implantation material in the distracted area. After completing the distraction, implantation material was injected into the distracted area, although no material was implanted into the distracted area of the control group. After implanting the materials, the distraction device was left in place for 6 weeks to allow for bony consolidation. Four dogs were allocated to each group. Two dogs in each group (total of 8 dogs) were killed 3 weeks after implantation of the material, and the other 8 dogs were killed after 6 weeks. New bone was generated in the distracted zone of all groups. In the calcium sulfate combined with chitosan group and calcium sulfate combined with hyaluronic acid group, the formation of active woven bone was observed throughout the distracted zone. Moreover, the new bone seemed to be nearly normal cortical bone at 6 weeks after implantation. In the chitosan group and hyaluronic acid group, the development of new bone was observed in the distracted zone at 6 weeks. The amount was less than that in the calcium sulfate combined with hyaluronic acid group and calcium sulfate combined with chitosan group. These findings suggest that calcium sulfate and its combined materials seem to be quite effective in early bony consolidation in distraction osteogenesis.

Role of BMP, betaig-h3, and chitosan in early bony consolidation in distraction osteogenesis in a dog model.

The purpose of this investigation was to study the effect of bone morphogenetic protein (BMP), transforming growth factor beta-induced gene h3 (betaig-h3), and chitosan on early bony consolidation in distraction osteogenesis in a dog model. Sixteen dogs were used for this study. The lateral surface of the mandibular body was exposed in the subperiosteal plane and the vertical osteotomy on the mandibular body was extended downward. An external distraction device was applied to the mandibular body, and the mandibular distraction was started 5 days after the operation at a rate of 2 mm/day up to a 10-mm distraction after 5 days. The experimental group was then divided into a control group, a BMP group, a betaig-h3 group, and a chitosan group, depending on the type of implantation material used in the distracted area. On the same day after completing the distraction, BMP, betaig-h3, or chitosan was implanted into the distracted area. No material was implanted into the distracted area in the control group. After implanting the materials, the distraction device was left in place for 7 weeks to allow for bony consolidation. Four dogs were allocated to each group. Two dogs in each group, a total of eight dogs, were killed 4 weeks after completing the distraction and the other eight dogs were killed after 7 weeks. Serial radiographs were obtained every week after completing the distraction. New bone was generated in the distracted zone in all groups. In the BMP group, the formation of active woven bone was observed throughout the distracted zone, and the new bone appeared to be nearly normal cortical bone 7 weeks after implantation. In the betaig-h3 and chitosan groups, the development of new bone was observed in the distracted zone after 7 weeks; however, the amount was less than that in the BMP group. In the control group, the new bone was observed at the edges of the distracted zone. These findings suggest that BMP seems to be very effective in early bony consolidation in distraction osteogenesis.