Micellized protein transduction domain-bone morphogenetic protein-2 accelerates bone healing in a rat tibial distraction osteogenesis model.

The clinical application of growth factors such as recombinant human bone morphogenetic protein-2 (rh-BMP-2), for functional bone regeneration remains challenging due to limited in vivo efficacy and adverse effects of previous modalities. To overcome the instability and short half-life of rh-BMP-2 in vivo, we developed a novel osteogenic supplement by fusing a protein transduction domain (PTD) with BMP-2, effectively creating a prodrug of BMP-2. In this study, we first created an improved PTD-BMP-2 formulation using lipid nanoparticle (LNP) micellization, resulting in downsizing from micrometer to nanometer scale and achieving a more even distribution. The micellized PTD-BMP-2 (mPTD-BMP-2) demonstrated improved distribution and aggregation profiles. As a prodrug of BMP-2, mPTD-BMP-2 successfully activated Smad1/5/8 and induced mineralization with osteogenic gene induction in vitro. In vivo pharmacokinetic analysis revealed that mPTD-BMP-2 had a much more stable pharmacokinetic profile than rh-BMP-2, with a 7.5-fold longer half-life. The in vivo BMP-responsive element (BRE) reporter system was also successfully activated by mPTD-BMP-2. In the in vivo rat tibia distraction osteogenesis (DO) model, micro-computed tomography (micro-CT) scan findings indicated that mPTD-BMP-2 significantly increased bone volume, bone surface, axis moment of inertia (MOI), and polar MOI. Furthermore, it increased the expression of osteogenesis-related genes, and induced bone maturation histologically. Based on these findings, mPTD-BMP-2 could be a promising candidate for the next-generation osteogenesis drug to promote new bone formation in DO surgery. STATEMENT OF SIGNIFICANCE: This study introduces micellized bone morphogenetic protein-2 (mPTD-BMP-2), a next-generation osteogenic supplement that combines protein transduction domain (PTD) and nano-sized micelle formulation technique to improve transduction efficiency and stability. The use of PTD represents a novel approach, and our results demonstrate the superiority of mPTD-BMP-2 over rh-BMP-2 in terms of in vivo pharmacokinetic profile and osteogenic potential, particularly in a rat tibial model of distraction osteogenesis. These findings have significant scientific impact and potential clinical applications in the treatment of bone defects that require distraction osteogenesis. By advancing the field of osteogenic supplements, our study has the potential to contribute to the development of more effective treatments for musculoskeletal disorders.

Cobalt-Doped Mesoporous Silica Coated Magnetic Nanoparticles Promoting Accelerated Bone Healing in Distraction Osteogenesis.

Introduction: Large bone abnormalities are commonly treated using distraction osteogenesis (DO), but it is not suitable for a long-term application; therefore, there is an urgent need for adjuvant therapy that can accelerate bone repair. Methods: We have synthesized mesoporous silica-coated magnetic nanoparticles doped with cobalt ions (Co-MMSNs) and assessed their capacity to quicken bone regrowth in a mouse model of DO. Furthermore, local injection of the Co-MMSNs significantly accelerated bone healing in DO, as demonstrated by X-ray imaging, micro-CT, mechanical tests, histological evaluation, and immunochemical analysis. Results: In vitro, the Co-MMSNs exhibited good biocompatibility and induced angiogenic gene expression and osteogenic development in bone mesenchymal stem cells. And the Co-MMSNs can promote bone regeneration in a rat DO model. Discussion: This study demonstrated the significant potential of Co-MMSNs to shorten the DO treatment duration and effectively reduce the incidence of complications.

Total flavonoids of Rhizoma drynariae ameliorate steroid­induced avascular necrosis of the femoral head via the PI3K/AKT pathway.

Steroid­induced avascular necrosis of the femoral head (SANFH) is a common orthopaedic disease that is difficult to treat. The present study investigated the effects of total flavonoids of Rhizoma drynariae (TFRD) on SANFH and explored its underlying mechanisms. The SANFH rat model was induced by intramuscular injection of lipopolysaccharides and methylprednisolone. Osteoblasts were isolated from the calvariae of neonatal rats and then cultured with dexamethasone (Dex). TFRD was used in vitro and in vivo, respectively. Haematoxylin and eosin staining was used to assess the pathological changes in the femoral head. Terminal deoxynucleotidyl transferase­mediated deoxyuridine triphosphate nick end labelling assay and flow cytometry were conducted to detect apoptosis of osteoblasts. The 2',7'­dichlorofluorescein­diacetate staining method was used to detect reactive oxygen species (ROS) levels in osteoblasts and the 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay was used to detect osteoblast proliferation. The expression of caspase­3, Bax, Bcl­2, VEGF, runt­related transcription factor 2 (RUNX2), osteoprotegerin (OPG), osteocalcin (OCN), receptor activator of nuclear factor κB ligand (RANKL) and phosphoinositide 3­kinase (PI3K)/AKT pathway related­proteins were detected via western blotting. It was found that TFRD reduced the pathological changes, inhibited apoptosis, increased the expression of VEGF, RUNX2, OPG and OCN, decreased RANKL expression and activated the PI3K/AKT pathway in SANFH rats. TFRD promoted proliferation, inhibited apoptosis and reduced ROS levels by activating the PI3K/AKT pathway in osteoblasts. In conclusion, TFRD protected against SANFH in a rat model. In addition, TFRD protected osteoblasts from Dex­induced damage through the PI3K/AKT pathway. The findings of the present study may contribute to find an effective treatment for the management of SANFH.

Rigid External Distraction with Intranasal Bone-borne Traction Hooks for Midfacial Hypoplasia.

Rigid external distraction is currently performed to correct cases of severe maxillary hypoplasia. As an improvement of this technique, we propose the use of an intranasal bone-borne traction hook. This study is a retrospective chart review of the intranasal bone-borne traction hooks used in the treatment of severe maxillary hypoplasia. There were 110 patients treated with the hooks from 2005 to 2017. The maximum traction force was 7.75 kg, and there were few complications encountered during distraction. There were 76 patients who had the hooks removed under local anaesthesia. A cephalometric analysis was conducted in 56 patients. The average advancement of A-point was 9.9 ± 4.2 mm, 8.4 ± 2.5 mm, 11.0 ± 3.7 mm, 17.9 ± 4.4 mm for the trans-sutural distraction osteogenesis (DO), maxillary anterior segment DO, Le Fort I osteotomy DO and Le Fort III/II osteotomy DO, respectively. The average changes of sella-nasion-point A (SNA) were 8.89 ± 4.30 degrees, 8.21 ± 3.17 degrees, 10.49 ± 3.26 degrees, and 15.10 ± 4.00 degrees, respectively. The A point-nasion-B point (ANB) also showed increases in all procedures with P < 0.001. In conclusion, this technique sufficiently advances the midface and ensures the scars are concealed in the nasal base. The traction hook can bear a large traction force, causes minimal complications and is easily removed.

Effect of Laser Bio-Stimulation on Mandibular Distraction Osteogenesis: An Experimental Study.

PURPOSE: The aim of this study was to evaluate the osseous response to laser bio-stimulation clinically and histologically during distraction osteogenesis (DO) induced in the mandibles of mongrel dogs. MATERIALS AND METHODS: Thirty dogs were divided into 3 groups of 10 (5 with and 5 without laser treatment) according to sacrifice periods (2, 4, and 8 weeks after distraction). DO was performed between the mandibular second and third premolars using an internal linear distractor. After a 7-day latency period, the distractor was activated at the rate of 1 mm per day for 10 days followed by a consolidation period during which the right mandibular side was irradiated with a diode laser (wavelength [λ], 970 nm; power, 2 W; spot size, 320 µm; total energy [E], 840 J), whereas the control group was not irradiated, after distraction. Histologic specimens were prepared and histomorphometric analysis of specimens was performed. RESULTS: Clinical examinations showed that the low-intensity laser diode had a pronounced effect on the quality and quantity of newly formed bone in the DO regenerate in the laser groups compared with the control groups. Histopathologic sections from laser groups I, II, and III displayed the bio-stimulatory effect of laser on new bone through an increased rate of osteoblast proliferation and differentiation, an accelerated rate of intramembranous ossification, and increased neoangiogenesis compared with the control groups. Moreover, the histomorphometric results showed that mean bone trabecular size, bone trabecular total area, and bony area fraction of the regenerate were larger and statistically significant (P < .05) especially in laser groups I and II (early stages of bone formation) compared with the control groups. CONCLUSION: The low-level diode laser had a positive role as a potential bio-stimulator and local inducer in enhancing bone formation during DO and resulted in early stability of the bone regenerate, a shorter total treatment time, and improved new bone quality and quantity.

Management of Osteomyelitis-Induced Massive Tibial Bone Defect by Monolateral External Fixator Combined with Antibiotics-Impregnated Calcium Sulphate: A Retrospective Study.

AIM: The present study is aimed at evaluating the effect of combined treatment on massive bone defect using radical debridement, antibiotic calcium sulphate, and monolateral external fixator. METHODS: 35 patients with tibial osteomyelitis received radical debridement, and during surgery antibiotics-impregnated calcium sulphate was used for filling the bone defect. Monolateral external fixator was used to manage the bone defect of average 95 (61-185) cm. RESULTS: Bone union was achieved in 34 patients (97.1%) with no reinfection. One case was presented with reinfection and further debridement was conducted. The average time for the utility of external fixation was 17 (7-32) months, and external fixation index (EFI) was 1.79 mon/cm. The mean follow-up duration after surgery was 33.7 (21-41) months. 19, 13, and 3 patients got excellent, good, and fair bone results, respectively. Meanwhile, functional results were excellent, good, fair, and poor in 13, 15, 6, and 1 patient. The most common complication was pain (100%) and superficial pin-tract infection (22.8%). Delayed maturation was incurred in 2 patients. CONCLUSION: Our study reveals that radical debridement combined with antibiotics-impregnated calcium sulphate can suppress infection, and distraction osteogenesis using monolateral external fixators plays an effective role in managing osteomyelitis-induced massive tibial bone defect.

Effect of strontium citrate on bone consolidation during mandibular distraction osteogenesis.

OBJECTIVES/HYPOTHESIS: Mandibular distraction osteogenesis (MDO) involves a lengthy consolidation phase where complications can occur. Strontium is an element that has been shown to improve bone healing. The objective of this study was to determine whether strontium citrate can be used to enhance bone healing during MDO in a rabbit model. STUDY DESIGN: Prospective animal model study. METHODS: Custom-made MDO devices were placed on 20 New Zealand White rabbits. After a 7-day latency period, distraction was performed at 1 mm/day for 5 days. The study group rabbits (n = 10) received oral strontium citrate; the other 10 rabbits served as controls. Mandibles were removed at the end of the consolidation period (4 weeks). Formation and healing of new bone were evaluated with microcomputed tomography, histology, and a three-point bending mechanical test. RESULTS: New bone formed in all animals, but the consolidation process was enhanced in rabbits that received strontium. The histological analysis showed that study group rabbits had more mature bone. Microcomputed tomographic images demonstrated significantly higher bone density for study group animals, and the three-point bending test results demonstrated that the maximum load of the study group specimens was significantly greater than that of the control group mandibles. CONCLUSIONS: Strontium citrate improved the formation of new bone in the current rabbit model of MDO. The prolonged consolidation period may be shortened with strontium citrate, which may also have the potential to reduce complications. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E212-E218, 2017.

Influence of a Magnetic Field and Laser Therapy on the Quality of Mandibular Bone During Distraction Osteogenesis in Rabbits.

PURPOSE: This study evaluated the use of low-level laser therapy (LLLT) and exposure to a magnetic field (MF) during distraction osteogenesis. MATERIALS AND METHODS: The sample consisted of 18 rabbits divided into 3 groups of 6 animals each: control, MF exposure (briefly, magnetized gold-coated washers were placed next to the distractor device), and LLLT exposure (830 nm applied every 48 hours over 4 points [dose, 5 J/cm2] during the consolidation period). The same distraction osteogenesis protocol was used in all 3 groups (0.5 mm every 12 hours for 1 week). RESULTS: Quantitative microscopic analysis of sections stained with hematoxylin and eosin showed a statistically significant difference in the amount of newly formed bone in the MF group compared with the LLLT group (P = .006). The number of cells with more than 3 argyrophilic nucleolar organizer regions also was significantly different between the LLLT and control groups (P = .038). CONCLUSION: Distraction osteogenesis effectively promoted bone lengthening. The LLLT group exhibited a larger amount of newly formed bone and a larger number of osteoblasts in the cell division phase, but the difference was not statistically relevant compared with the control group.

The Radiological and Stereological Analysis of the Effect of Low-Level Laser Therapy on the Mandibular Midline Distraction Osteogenesis.

OBJECTIVE: The aim of this study was to evaluate the effect of low level laser therapy (LLLT) on bone mineral density by using high-resolution computerized tomography (HR-CT) and stereology in patients subjected to mandibular midline distraction. METHODS: Nine patients between the ages of 13 and 16 years with mandibular transverse deficiency (>5 mm) were evaluated. Mandibular midline distraction osteogenesis was performed for all the patients. The patients were divided into 2 groups: the control group (n = 4) and the laser group (n = 5). GaAlAs, 830 nm wavelength, power of 40 mW, energy of 8.4 J/cm2 dose per spot, was directly applied from 2 points on the mandibular midline. The laser was applied in 8 treatment sessions at 48-hour intervals. Bone mineral density and volume of the newly formed bone were analyzed using HR-CT and stereological methods. RESULTS: A higher bone mineral density rate was found in the laser group (P < 0.05). A higher newly formed immature bone rate was found in the control group (P < 0.001). These findings suggest that more mature bone may also have a greater mineral organization than that of immature newly formed bone, which is shown by HR-CT and stereological results. CONCLUSIONS: The retention period can be shortened and mineralization may be increased by using LLLT in mandibular distraction osteogenesis.

Effects of laser vs ultrasound on bone healing after distraction osteogenesis: A histomorphometric analysis.

OBJECTIVE: To assess the effects of low-level laser irradiation vs ultrasound irradiation on bone healing after distraction osteogenesis. MATERIALS AND METHODS: Distraction osteogenesis was performed with rapid maxillary expansion devices (Hyrax-Morelli, Sorocaba, São Paulo Brazil) in 24 rabbits (Oryctolagus cuniculus). After a 2-day latency period, the distraction devices were activated for 10 days at a rate of 1 mm/d. Four groups of six animals were treated as follows: (1) control, (2) laser irradiation on the right side, (3) ultrasound irradiation on the right side, and (4) laser irradiation on the right side and ultrasound on the left side. Histomorphometric analysis was used to assess the bone healing area. Analysis of variance was used to perform the statistical analyses. RESULTS: The influence of low-intensity laser associated with ultrasound irradiation on bone healing was statistically significant. The analyses showed the greatest amount of bone healing in the jaws of animals in group 4, which received treatment with both ultrasound and laser. CONCLUSION: This study concluded that bone healing is accelerated with the application of laser irradiation. The greatest effects were observed with combined ultrasound and laser treatment.

Effects of the hyperbaric oxygen on de novo bone formation during periosteal distraction.

OBJECTIVE: The purpose of this study was to investigate the effect of hyperbaric oxygen (HBO) therapy on de novo bone formation during periosteal distraction (PD). MATERIALS AND METHODS: Periosteal distraction was performed in 24 mature male New Zealand rabbits using a custom-designed device placed on the lateral surface of the mandibular corpus. Twelve rabbits (group H) were given adjunctive HBO treatment, whereas 12 rabbits (group N) were kept in a normal environment (normobaric oxygen). After a 7-day latency period, the same distraction protocol was applied to both groups. However, the rabbits in group H were treated with pure oxygen at 2.4 atm absolute for 25 times. Both groups were further divided into 2 subgroups and killed after consolidation periods of 4 and 8 weeks. Photodensitometric and histologic analyses were performed to evaluate the newly formed bone. RESULTS: There was no significant difference between the 4-week consolidated HBO group and the 8-week consolidated normobaric oxygen subgroup (P = 0.229). Moreover, there was better bone formation in the 8-week HBO group than in the 8-week control group. CONCLUSION: The results of this study indicate that PD with HBO could be used to increase the quality and the quantity of the bone newly formed by PD.

Cellular effect of low-level laser therapy on the rate and quality of bone formation in mandibular distraction osteogenesis.

OBJECTIVE: Therapeutic lasers have been shown to influence bone physiology and repair. The aim of the present investigation was to evaluate the use of a GaAlAs (λ:810 nm) laser in distraction osteogenesis. BACKGROUND DATA: To reduce problems associated with distraction osteogenesis and shorten the time required for treatment, it is desirable to accelerate the process of bone formation. MATERIALS AND METHODS: Eighteen male rabbits underwent corticotomy of mandibular body, and customized distraction devices were inserted. After a 5-day latency period, the mandibles were lengthened by 0.5 mm/day for 10 days. The rabbits were divided into two groups. A GaAlAs (λ: 810 nm) laser beam with the parameters power (P), 200 mW; energy density (ED), 3 J/cm(2); time (T), 7.5 sec; power density (PD) 400 mW/cm(2); energy (E) 1.5 J and spot diameter, 0.8 mm was directed medially and laterally in the study group; the control group received no laser treatment. The exposure continued with six more doses every other day. Three rabbits from each of the two groups were euthanized on the 10th, 20th, and 40th days post-distraction (consolidation) period. RESULTS: Both light microscopy and scanning electron microscopic (SEM) analysis showed significant improvement in new bone formation in the study group at the 10th and 20th days compared with the control group, but the difference was more prominent on the 10th day. By the 40th day, there were no significant differences between the two groups. CONCLUSIONS: This study shows that a low-level GaAlAs (λ:810 nm; P, 200 mW) laser hastens new bone formation only in the early stages of the consolidation period in distraction osteogenesis, and has no significant effect in later stages.

The marine sponge-derived inorganic polymers, biosilica and polyphosphate, as morphogenetically active matrices/scaffolds for the differentiation of human multipotent stromal cells: potential application in 3D printing and distraction osteogenesis.

The two marine inorganic polymers, biosilica (BS), enzymatically synthesized from ortho-silicate, and polyphosphate (polyP), a likewise enzymatically synthesized polymer consisting of 10 to >100 phosphate residues linked by high-energy phosphoanhydride bonds, have previously been shown to display a morphogenetic effect on osteoblasts. In the present study, the effect of these polymers on the differential differentiation of human multipotent stromal cells (hMSC), mesenchymal stem cells, that had been encapsulated into beads of the biocompatible plant polymer alginate, was studied. The differentiation of the hMSCs in the alginate beads was directed either to the osteogenic cell lineage by exposure to an osteogenic medium (mineralization activation cocktail; differentiation into osteoblasts) or to the chondrogenic cell lineage by incubating in chondrocyte differentiation medium (triggering chondrocyte maturation). Both biosilica and polyP, applied as Ca²âº salts, were found to induce an increased mineralization in osteogenic cells; these inorganic polymers display also morphogenetic potential. The effects were substantiated by gene expression studies, which revealed that biosilica and polyP strongly and significantly increase the expression of bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP) in osteogenic cells, which was significantly more pronounced in osteogenic versus chondrogenic cells. A differential effect of the two polymers was seen on the expression of the two collagen types, I and II. While collagen Type I is highly expressed in osteogenic cells, but not in chondrogenic cells after exposure to biosilica or polyP, the upregulation of the steady-state level of collagen Type II transcripts in chondrogenic cells is comparably stronger than in osteogenic cells. It is concluded that the two polymers, biosilica and polyP, are morphogenetically active additives for the otherwise biologically inert alginate polymer. It is proposed that alginate, supplemented with polyP and/or biosilica, is a suitable biomaterial that promotes the growth and differentiation of hMSCs and might be beneficial for application in 3D tissue printing of hMSCs and for the delivery of hMSCs in fractures, surgically created during distraction osteogenesis.

Low-intensity pulsed ultrasound shortens the treatment time in tibial distraction osteogenesis.

PURPOSE: Low-intensity pulsed ultrasound (LIPUS) has been used successfully to accelerate healing of fresh fractures and non-unions. It also improved callus maturation with distraction osteogenesis in animal trials. However, only few clinical studies are available to support its widespread use for the latter indication in humans. METHODS: Twenty-one patients undergoing callus distraction for posttraumatic tibial defects were randomized into two groups: the trial group (12 men; mean age 32 years) which received 20 minutes LIPUS daily during treatment and the control group (six men and three women; mean age 29 years) without LIPUS treatment. The Ilizarov ring fixator was used in all cases. Results were examined clinically and radiologically, analysing callus maturation with a computer-assisted measurement. RESULTS: Patients in the LIPUS group needed a mean of 33 days to consolidate every 1 cm of new bone in comparison to 45 days in the control group. The healing index was therefore shortened by 12 days/cm in the LIPUS group. This means that callus maturation was 27 % faster in the LIPUS group. The fixator time was shortened by 95 days in the LIPUS group. The overall daily increase in radiographic callus density was 33 % more in the LIPUS group than in the control group. CONCLUSIONS: LIPUS treatment is an effective non-invasive adjuvant method to enhance callus maturation in distraction osteogenesis. With the help of this treatment, the healing time and the duration of external fixation can be reliably shortened.

Histomorphometrical and radiological comparison of low-level laser therapy effects on distraction osteogenesis: experimental study.

Distraction osteogenesis (DO) is the application of traction to the callus formed between bone segments and stimulation of bone formation by creating stress on the callus with this traction. Shorten the duration of DO and increasing the capacity of bone formation is important to prevent the possible complications of DO. For this reason, it was considered that low-level laser therapy (LLLT) may affect positively DO and it can decrease the complication range by shortening the period. Unilateral mandibular distractors were applied on 16 female white New Zealand rabbit to prove this hypothesis with micro CT, plain radiograph and histomorphometric analyses. Eight rabbits were applied LLLT with GaAlAs laser on the distraction area during the distraction period. On the post-distraction 28th day, four rabbits from study group and four rabbits from control groups were sacrificed. The rest of the rabbits were sacrificed on post-distraction 56th day. As a result of this study, significant positive effects of LLLT on post-distraction 28th day were revealed with all analyses. In histomorphometrical analyses, new bone formation was significantly higher in short-term laser applied group comparing to that of short-term control group (p = 0.029). In both microCT and plain radiograph, the highest radioopacity values were observed in short-term laser group when compared with that of the controls (p = 0.043 and p = 0.025, respectively). Even though LLLT increased the healing capacity on short-term, it was not sufficient on long-term (post-distraction 56th day) healing. LLLT application on distraction period, activate healing on bone so it may decrease DO period. The result of this study should be supported with clinical studies and the most effective laser source, dose and application time should be revealed with experimental and clinical studies.

Guide surgery osteotomy system (GSOS) a new device for treatment in orthognathic surgery.

INTRODUCTION: This article proposes an innovative and revolutionary diagnostic and therapeutic protocol for performing dentoalveolar osteotomies in office under local anaesthesia with piezoelectric surgery using a surgical acrylic guide produced through software-based planning. METHODS: The method was applied in the correction of crossbites, changing in the curve of Spee, incisal decompensations and dental ankylosis. Performing a preoperative CT with a special splint, optical scanning of the models and the subsequent planning with software has enabled us to produce a model with rapid prototyping with the design of the osteotomy on which the surgical guide was shaped, the use of the guide associated with piezoelectric surgery, allowed to perform surgery under local anaesthesia, with minimal invasiveness and high accuracy. RESULTS: Dentoalveolar immediate movements, with preservation of the roots of teeth involved, allow for rapid treatment of malocclusions which would be long and often difficult if not impossible to treat with orthodontics only. Dentoalveolar osteotomies associated to osteodistraction concepts, allow the orthodontist to achieve with accuracy the objectives required by the treatment plan. CONCLUSIONS: GSOS is a new method, which, utilizing 3D optical scanning images of models, software and piezoelectric surgery, allows to perform dentoalveolar movements which may be dangerous to the roots or for the periodontal support, with orthodontics only. It dramatically reduces total surgical-orthodontic treatment time, with obvious great patient satisfaction.

[Effect of Eupolyphaga Sinensis Walker on mandibular distraction osteogenesis in rabbits].

OBJECTIVE: To study the effect of Eupolyphaga Sinensis Walker on mandibular distraction osteogenesis (DO) in rabbits. METHODS: 30 Japanese white rabbits (weight 2.0-2.5 kg, about 3 months old) were divided randomly into control group (n = 15) and experimental group (n = 15). Unilateral mandibular DO models were established at the right mandible of the rabbits. Distraction was started 7 days after the surgery at the speed of 0.4 mm per time twice a day and continued for 10 days. From the first day of distraction to the day of execution, the experimental group rabbits were fed with 2 g of ESW power once a day at 9 o' clock. Three animals in each group were executed respectively at 24 hours, 72 hours, 1 week, 4 weeks and 7 weeks after completion of distraction, and the specimens of DO were harvested. The general observation, X-ray examination, histological study and immunohistochemical staining of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) were performed. The images of immunohistochemical staining of BMPs and VEGF were analyzed by the image analysis software, and the results were analyzed by statistical software SPSS 17.0. RESULTS: The rate of the new bone formation in the experimental group was faster than that in the control group, and the immunohistochemical staining of BMPs and VEGF in the experimental group was higher than that in the control group. CONCLUSIONS: ESW can promote the formation of the new bone in the distracted gap during mandibular DO in rabbits, which may be due to its enhancement effect on the expression of BMPs and VEGF.

Enhancement of bone consolidation in mandibular distraction osteogenesis: a contemporary review of experimental studies involving adjuvant therapies.

BACKGROUND: One of the major disadvantages of mandibular distraction osteogenesis (MDO) is the prolonged time required for consolidation of the regenerate bone. The objective of the present study is to perform a contemporary review of various adjuvant therapies to enhance bone consolidation in MDO. METHODS: A PubMed search for articles related to MDO, along with the references of those articles, was performed. Inclusion and exclusion criteria were applied to all experimental studies assessing adjuvant therapies to enhance bone consolidation. RESULTS: A total of 1414 titles and abstracts were initially reviewed; 61 studies were included for full review. Many studies involved growth factors, hormones, pharmacological agents, gene therapy, and stem cells. Other adjuvant therapies included mechanical stimulation, laser therapy, and hyperbaric oxygen. Majority of the studies demonstrated positive bone healing effects and thus adjuvant therapies remain a viable strategy to enhance and hasten the consolidation period. CONCLUSION: Although most studies have demonstrated promising results, many questions still remain, such as optimal amount, timing, and delivery methods required to stimulate the most favorable bone regeneration. As well, further studies comparing various adjuvant therapies and documentation of long-term adverse effects are required prior to clinical application.

Femoral bone transport by a monolateral external fixator with or without the use of intramedullary nail: a single-department retrospective study.

BACKGROUNDS: Treatment for bone defect remains a challenge for orthopedists. Bone transport gives an effective alternative, which can be performed with an external fixator alone or combined with an intramedullary nail. Each has its advantages and disadvantages. We present a retrospective study to find out the optimal choice by evaluating the outcomes of treatment for femoral bone defect with two methods. METHODS: Two groups of patients, the monolateral external fixator alone (group A, n = 13) and the monolateral external fixator combined with intramedullary nail (group B, n = 15), were compared. Duration of the external fixator, external fixator index, radiographic consolidation index, complication, and total cost for treatment was also recorded. A modified classification of the Association for the Study and Application of the Method of Ilizarov (ASAMI) was used to assess results in two groups of patients; another SF-36 health survey questionnaire was used to assess the life qualities patients of two groups. RESULTS: Healing was achieved in 13/13 and 13/15 of the two groups, respectively. The rates of complications were significantly higher in the group A. Two patients performed amputations because of persistent deep infections in group B. Statistically significant difference was found when comparing ASAMI scores and categories of the SF-36 health survey. CONCLUSIONS: Bone transport by monolateral external fixator with the use of intramedullary nail reduces the incidence of complication and the duration of external fixator time that give patients a better life quality in both physical and emotional. However, if chronic osteitis exists, bone transport should be treated with monolateral external fixator alone due to a lower rate of amputations.