Objectives. This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats. Methods. The mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software. Results. There were highly significant correlations between undecalcified histological sections and micro-CT for all parameters (bone volume density (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp))in the mandible and tibia. Bone histomorphometric parameters analysed by both methods exhibited significant differences among sham, OVX, and OVX-ZOL groups. There were significant correlations between mandible and tibia in BV/TV, BS/BV, and Tb.Sp. Conclusions. Micro-CT is a complementary tool to histological sections in basic research that could improve our understanding of bone histomorphometry. The mandible can be used as an effective site to assess bone morphometry of OVX or metabolic bone disease rat models. Cite this article: H. Liu, W. Li, Y. S. Liu, Y. S. Zhou. Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT. Bone Joint Res 2016;5:253–262

The Temporomandibular joint (TMJ) is a complex and important joint for daily activities, and the alloplastic implant is recommended as the best solution, after repeated surgeries, failed autogenous grafts, highly inflammatory metabolic arthritis, fibrous or bony ankyloses. Some complications in total TMJ replacement are associated with implant design, screw fixation failure, implant displacement, fibrous tissue formation, (Speculand, et al. 2000). Some numeric studies evaluate the number of screws needed to guarantee the good fixation and suggest a minimum of three (Ramos et al. 2015), but is a controversy conclusion. The Biomet Microfixation TMJ stock prosthesis, Jacksonville, FL, USA is one of the three or four in the market. Clinical studies published by this device between 2005 and 2015 indicate a success rate of around 84 to 91% with improvements in mouth opening, a decrease in pain score and improved quality of life. The present study analyses experimentally the load transfer of this device. The intact, clean cadaveric ramus was instrumented with four rosettes model (KFG-1-120-D17-11 L3M2S, by Kywoa Electronic Instruments Co™, Japan), one in lateral region, two in lateral region and one in lingual face. The condyle was loaded with the temporal reaction; the load was applied constant velocity of 1mm/min in three continuum phases and with three stops at 100N, 200N and 300N. Next, the Biomet microfixation implant was fixed to the same cadaveric mandibular ramus after resection. The implant was 50mm in length. It was fixed with five 6AL/4V Titanium self-tapping screws with 2.7mm diameter were long enough to establish a bi-cortical support. The screws were screwed into the bone with a torque-screwdriver a constant torque of 0.2Nm. The same rosettes were analyzed before and after implantation and the mandible displacement two. The experimental results for the mandibular ramus present a linear behavior up to 300N load in condyle, with the Biomet implant influencing strain distribution; the maximum influence was near the implant (rosette #4) is around 59%. The average vertical displacement of the mandibular ramus (300N) was measured by machine: 1.18 (±0.02) mm for the intact mandibular ramus and 1.21 (±0.02) mm for the implanted one, which represents a 2.8% differences between the experimental models and reduce of stiffness. The maximum principal strain deformation was observed in the rosette #3 with 1360µε more 20% than the intact mandible for 300N of reaction. The experimental results show that the Biomet TMJ mandibular ramus implant changes the load transfer in the ramus, compared to the intact, with its strain shielding effect. The results indicate the minimum number of screws is three to guarantee a good load transfer but the surface preparation of condyle presents an important factor

Background. Radiotherapy has contributed with a significant and impressive stride to the survival rates of oral cancer patients. However, quality and alterations in the biochemical composition of bones used for dental implantation after radiotherapy in cancer patients is always a critical and debatable factor. The aim of this study was to determine compositional alterations in human mandible bone after irradiation using Raman microspectroscopy. Methods. A total of 36 bone biopsies (21-control, 4-cancer and 11-irradiated) obtained from 36 patients during implant surgery were used. Raman measurements were carried out using a Bruker Senterra LX200 dispersive Raman spectrometer. Data acquisition points were determined under pathological supervision. Three measurements from different locations were conducted with a spot size of 10 microns. Spectra were acquired for 60s and averaged over 5-accumulations. Both mineral and matrix constituents were analysed by computing area associated with of phosphate (958 cm-1), carbonate (1070 cm-1), collagen (amide III) and matrix (amide I) bands using in-house MATLAB-based software. Unpaired student ‘t’ test was employed to measure level of significance. Results. Absolute mineral contents (phosphate and carbonate) were higher in cancer specimens

Introduction. The main postoperative complications in fixation of ulna shaft fractures are non-union and implant irritation using currently recommended 3.5-mm locking compression plates. An alternative approach using a combination of two smaller plates in orthogonal configuration has been proposed. The aim of this study was to compare the biomechanical properties of a single 3.5-mm locking compression plate versus double plating using one 2.5-mm and one 2.0-mm mandible plate in a human ulna shaft fracture model. Method. Eight pairs human ulnar specimens with a standardized 10-mm fracture gap were pairwise assigned for instrumentation with either a single 3.5-mm plate placed posteriorly, or for double plating using a 2.5-mm and a 2.0-mm mandible plate placed posteriorly under the flexor muscles and laterally under the extensor muscles. All constructs were initially non-destructively biomechanically tested in axial compression, torsion, and bending, which was followed by cyclic torsional loading to failure. Interfragmentary movements were monitored by means of optical motion tracking. Result. There were no significant differences between the two plating techniques for axial stiffness (p=0.335), torsional stiffness in supination (p=0.462), torsional stiffness in pronation (p=0.307), medio-lateral bending stiffness (p=0.522), and antero-posterior bending stiffness (p=0.143). During cyclic torsional loading over the first 3000 cycles, there were no significant differences between the two plating techniques for shear displacement across the fracture gap, p=0.324. The numbers of cycles until clinically relevant failure of 5° angular deformation were 1366±685 for double plating and 2024±958 for single plating, which was statistically non-significantly different, p>0.05. The constructs treated with both plating techniques failed due to bone breakage at the most distal screw. Conclusion. From a biomechanical perspective double plating of ulna shaft fractures using a 2.5-mm and a 2.0-mm locking mandible plate demonstrated equivalent fixation strength as conventional plating using a single 3.5-mm locking compression plate

The aim of the ongoing projects was to demonstrate the efficacy of autologous bone marrow derived stem cells (MSC) combined with biomaterial to induced new bone formation in a randomized multicenter controlled clinical trial. Patients with a need for bone reconstruction of residual edentulous ridges in both the mandible and maxilla due to bone defects with a vertical loss of alveolar bone volume and/or knife edge ridges (≤ than 4,5 mm) unable to provide adequate primary stabilization for dental implants were included in the clinical study. Autologous bone marrow MSC were expanded, loaded on BCP and used to augment the alveolar ridges. After five months bone biopsies were harvested at the implant position site and implants were installed in the regenerated bone. The implants were loaded after 8–12 weeks. Safety, efficacy, quality of life and success/survival were assessed. Five clinical centers, 4 different countries participated. Bone grafts harvested from the ramus of the mandibles were used as control in the projects

Introduction. Achieving an appropriate primary stability after implantation is a prerequisite for the long-term viability of a dental implant. Virtual testing of the bone-implant construct can be performed with finite element (FE) simulation to predict primary stability prior to implantation. In order to be translated to clinical practice, such FE modeling must be based on clinically available imaging methods. The aim of this study was to validate an FE model of dental implant primary stability using cone beam computed tomography (CBCT) with ex vivo mechanical testing. Method. Three cadaveric mandibles (male donors, 87-97 years old) were scanned by CBCT. Twenty-three bone samples were extracted from the bones and conventional dental implants (Ø4.0mm, 9.5mm length) were inserted in each. The implanted specimens were tested under quasi-static bending-compression load (cf. ISO 14801). Sample-specific homogenized FE (hFE) models were created from the CBCT images and meshed with hexahedral elements. A non-linear constitutive model with element-wise density-based material properties was used to simulate bone and the implant was considered rigid. The experimental loading conditions were replicated in the FE model and the ultimate force was evaluated. Result. The experimental ultimate force ranged between 67 N and 789 N. The simulated ultimate force correlated better with the experimental ultimate force (R. 2. =0.71) than the peri-implant bone density (R. 2. =0.30). Conclusion. The developed hFE model was demonstrated to provide stronger prediction of primary stability than peri-implant bone density. Therefore, hFE Simulations based on this clinically available low-radiation imaging modality, is a promising technology that could be used in future as a surgery planning tool to assist the clinician in evaluating the load-bearing capacity of an implantation site. Acknowledgements. Funding: EU's Horizon 2020 grant No: 953128 (I-SMarD). Dental implants: THOMMEN Medical AG

Recently, a new generation of superior clavicle plates was developed featuring the variable-angle locking technology for enhanced screw positioning and optimized plate-to-bone fit design. On the other hand, mini-fragment plates used in dual plating mode have demonstrated promising clinical results. However, these two bone-implant constructs have not been investigated biomechanically in a human cadaveric model. Therefore, the aim of the current study was to compare the biomechanical competence of single superior plating using the new generation plate versus dual plating with low-profile mini-fragment plates. Sixteen paired human cadaveric clavicles were assigned pairwise to two groups for instrumentation with either a 2.7 mm Variable Angle Locking Compression Plate placed superiorly (Group 1), or with one 2.5 mm anterior plate combined with one 2.0 mm superior matrix mandible plate (Group 2). An unstable clavicle shaft fracture AO/OTA15.2C was simulated by means of a 5 mm osteotomy gap. All specimens were cyclically tested to failure under craniocaudal cantilever bending, superimposed with bidirectional torsion around the shaft axis and monitored via motion tracking. Initial stiffness was significantly higher in Group 2 (9.28±4.40 N/mm) compared to Group 1 (3.68±1.08 N/mm), p=0.003. The amplitudes of interfragmentary motions in terms of craniocaudal and shear displacement, fracture gap opening and torsion were significantly bigger over the course of 12500 cycles in Group 1 compared to Group 2; p≤0.038. Cycles to 2 mm shear displacement were significantly lower in Group 1 (22792±4346) compared to Group 2 (27437±1877), p=0.047. From a biomechanical perspective, low-profile 2.5/2.0 dual plates demonstrated significantly higher initial stiffness, less interfragmentary movements, and higher resistance to failure compared to 2.7 single superior variable-angle locking plates and can therefore be considered as a useful alternative for diaphyseal clavicle fracture fixation especially in unstable fracture configurations

Implant removal after clavicle plating is common. Low-profile dual mini-fragment plate constructs are considered safe for fixation of diaphyseal clavicle fractures. The aim of this study was to investigate: (1) the biomechanical competence of different dual plate designs from stiffness and cycles to failure, and (2) to compare them against 3.5mm single superoanterior plating. Twelve artificial clavicles were assigned to 2 groups and instrumented with titanium matrix mandible plates as follows: group 1 (G1) (2.5mm anterior+2.0mm superior) and group 2 (G2) (2.0mm anterior+2.0mm superior). An unstable clavicle shaft fracture (AO/OTA15.2C) was simulated. Specimens were cyclically tested to failure under craniocaudal cantilever bending, superimposed with torsion around the shaft axis and compared to previous published data of 6 locked superoanterior plates tested under the same conditions (G3). Displacement (mm) after 5000 cycles was highest in G3 (10.7±0.8) followed by G2 (8.5±1.0) and G1 (7.5±1.0), respectively. Both outcomes were significantly higher in G3 as compared to both G1 and G2 (p≤0.027). Cycles to failure were highest in G3 (19536±3586) followed by G1 (15834±3492) and G2 (11104±3177), being significantly higher in G3 compared to G2 (p=0.004). Failure was breakage of one or two plates at the level of the osteotomy in all specimens. One G1 specimen demonstrated failure of the anterior plate. Both plates in other G1 specimens. Majority of G2 had fractures in both plates. No screw pullout or additional clavicle fractures were observed among specimens. Low-profile 2.0/2.0 dual plates demonstrated similar initial stiffness compared to 3.5mm single plates, however, had significantly lower failure endurance. Low-profile 2.5/2.0 dual plates showed significant higher initial stiffness and similar resistance to failure compared to 3.5mm single locked plates and can be considered as a useful alternative for diaphyseal clavicle fracture fixation. These results complement the promising results of several clinical studies

In the area of 3D printing, more and more maxillofacial surgery departments are equipped with 3D printers to build their own anatomical models or surgical guides. Prior to be printable, the patients' DICOM imaging data has to be converted to a 3D virtual model, a 3D mesh. The file format most commonly used is the STL (Standard Tesselation Language) file format. Many programs exist that are able to convert DICOM data to STL files. Commercial software, such as Surgicase CMF© are FDA- and CE-approved whereas free programs, available online do not have the approval. However, the latter are often used anyway because of financial reasons. In this article, we investigate whether 6 of these software solutions are equivalent or not. Thin slice CT imaging data of a patient's mandible (in DICOM file format) was converted to STL meshes with 6 different software solutions. One commercial program, Surgicase CMF©, was used to build the reference model. Then 5 free programs were used to create 5 models of the same mandible, specifying the same thresholding parameters: InVesalius 3.0, 3DimViewer 2.2.4, 3D Slicer, itk-Snap and Seg3D. All of these models were loaded in Netfabb Basic 6.4 to retrieve dimensional data, geometric information and the number of holes in each mesh. Finally, the models were then compared to the reference model using CloudCompare 2.6.2. All models created with free software differed from the reference model in the 3 dimensions. Mean length difference was −0.74 mm [−2.06; −0.32] (SD: 0.74), mean width difference −0.45 mm [−0.76; −0.25] (SD: 0.19) and mean height difference was 0.41 mm [0.14; 0.62] (SD: 0.18). Although the height was increased in all models, both the length and width were systematically decreased, resulting in an average decrease of volume of −7.1 cm. 3. [−7.45; −6.77] (SD: 0.32). The number of triangles used to create each mesh ranged from 20944 to 368244, resulting in a variation of the file size from 1023 Ko to 80462 Ko (0.16 to 12.70 times the file size of the reference model). Two of the free programs created meshes with errors, such as the presence of holes (non-watertight meshes) that could be repaired with Netfabb. Free programs able to convert volume imaging data to a printable virtual mesh do not provide equivalent results. Variations were noted in the three plane of space with a systematic difference between free programs and the commercial FDA-approved one. While the length and width were less than a millimeter different to the reference, the dimension that most varied was the length with a difference reaching −2.06 mm with itk-Snap. Geometric data also varied significantly, the number of triangles composing the meshes being much different than the reference, resulting in variable file sizes. This traduces the fact that algorithms used by the programs are not the same. In the era of 3D printing made directly accessible in surgical departments, great attention should be paid to the accuracy of the models created with free software

Introduction: The evolution of biomaterials has helped immensely the quality of reconstruction as well as the progress of medical specialties. The evolution of biomaterials for reconstruction has helped creating ones that are absorbable, look alike human tissues and contribute to daily activities of human body. Synthetic bone grafts, metal substitutes of bones and complex special tissues are the current therapeutic practice. Material and methods: In this presentation maxillofascial reconstructions will be shown where Orthopaedic biomaterials have been successfully used. Patients with large bone cysts that have been treated with or without grafting and titanium or stainless steel plates. Patients with large bone defects of the mandible that were filled with bone grafts or absorbable membranes Patients with Ca of the mandible reconstruction with fibular graft and osteosynthesis. Conclusion: The evolution of new biomaterials as well as the experience of Orthopaedic surgery has proved the essential step of contemporary Maxillofascial surgery

Intraosseous schwannoma is a rare benign neoplasm, which most commonly arises in the head and neck region particularly the mandible, due to the long intraosseous path of sensory nerves in the mandible. We present a 27-year-old lady with an unusual presentation of an intraosseous schwannoma of the first metatarsal. There is only one report published previously of an intraossous schwannoma of the lesser metatarsal bone of the foot. A 27-year-old woman presented with painful left forefoot following a trip while walking. Plain radiographs demonstrated a pathological fracture through a lytic lesion of the first metatarsal of the left foot. MRI scan using axial T1-weighted spin echo and axial and sagittal T2-weighted gradient echo showed an amorphous mass occupying the medulla of the bone but with a breach of the plantar aspect of cortex with apparent localised destruction. Ultrasound-guided biopsy was performed. Haematoxylin and Eosin stained specimen sections showed a proliferation of spindle cells of alternating hypercellularity and hypocellularity. This case was managed by curettage and grafting with autograft and synthetic bone substitute. At two-year follow-up, the radiographs showed complete graft incorporation and a healed cyst. The patient was clinically asymptomatic with return of full functions. There were no clinico-radiological findings to suggest any recurrence. Due to rarity and non-specific clinico-radiological features, this case illustrates the necessity of a multi-disciplinary approach with an accurate histological diagnosis in combination with radiological and clinical appearances

Bilateral mandibular lengthening is widely accepted during mandibular distraction osteogenesis. However, distraction osteogenesis are sometimes associated with clinical complications such as open bite deformity, lateral displacement of temporo-mandibular joint, premature consolidation and pin loosening. Although distraction osteogenesis aims to develop pure tensile strain on the regenerate tissue however, in real life situation due to differences in device orientation, materials and misalignment it is often subjected to complex stress and strain regimes. The objective of this study was to characterise the mechanical environment (stress and strain) in the Finite Element Models (FEM) of regenerate tissue during two different device orientations:. (a) device placed parallel to the mandibular body. (b) device placed parallel to the axis of distraction. Furthermore, the influence of misalignment from above two idealised orientations was also investigated. The distraction protocol in this study was similar to previous study of Loboa et al (2005). FE models were developed at four stages: end of latency, distraction day two, distraction day five and distraction day eight. At each time period a distraction of 1mm was applied to the model as it is most widely used distraction rate. In these models two primary distraction vectors were simulated; first when the device is parallel to the body of the mandible and second when the device is parallel to the axis of distraction. Results indicate that when the device is placed parallel to the mandible the effect of distraction vector variation due to misalignment in transverse plane (±150 at an interval of 50 ; + indicate lateral and indicates medial) is symmetric and variation in the stress and strain regimes on regenerative tissue are less than 3%. However, when the device is placed parallel to axis of distraction the corresponding change is asymmetric and almost double in magnitude. The greatest differences were seen when misalignment is towards lateral side (+150). Similarly in the sagittal plane variations up to 17% were developed due to 0- 400 change in the distraction vector orientation. Thus the orientation of device which determines the distraction vector plays an important role in determining the mechanical environment around regenerative tissue. The results suggest that implications of misalignment of the device and its sensitivity from the ideal situation should be well understood during clinical planning

Aims

Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma.

Introduction:. Skeletal involvement in non-Hodgkin lymphoma in HIV/AIDS is rarely reported. The bone lesions can have a spectrum of radiological features. Aims:. The aim of the study was to review the radiological features of non-Hodgkin lymphoma (NHL) involving the bone in HIV positive patients. Methodology:. All cases of NHL involving bone in HIV positive patients diagnosed histopathologically were recorded retrospectively between September 2002 and December 2013. Clinical manifestations, radiological features and haematological investigations were analysed from the patients' records. Histopathological subtypes were analysed from slides. Results:. 105 Cases of lymphoma involving bone were recorded. Of these, 46 patients met the criteria of being HIV positive and diagnosed with NHL involving bone. The male to female ratio was equal, the age ranged from 14 to 51 years (average 35 years), the absolute CD 4 count ranged from 17 to 307 (average 100). The sites of involvement were:- vertebrae (22), ribs (8), pelvis (6), femur (3), mandible (3), humerus (2), sternum (1) and clavicle (1). Vertebral involvement was multifocal with a large extradural soft tissue mass in 17 cases and solitary in 5 cases. Pathological fractures were seen in 4 cases of long bone involvement. Most patients presented with a high grade large B cell non-Hodgkin lymphoma with CD20 immunopositivity. Conclusion:. Primary bone lymphoma is a rare disease, accounting for approximately 3% of all primary bone malignancies and 4% to 7% of all extranodal lymphomas in the general population. The prevalence of primary and secondary bone lymphoma is very high in HIV positive patients. The disease is very aggressive, presenting in patients with low CD 4 count and the prognosis is poor. The radiologic patterns can be lytic, blastic or subtle changes, solitary or multifocal. The diagnosis of skeletal NHL is made on histopathology

Background. The transverse skin incision for anterior cervical spine surgery is not extensile, thus it must be made at the accurate level. The use of palpable bony landmarks is unreliable due to anatomical variations and pre-operative fluoroscopy to identify the level takes up operating room time, increases the radiation dose to the patient and increases the overall cost of the operation. Objective. To describe a simple, fast and inexpensive method of accurate transverse skin incision placement for anterior cervical spine surgery and to report on its use in 54 consecutive adult patients. Patients and Methods. In each case a ratio was recorded on the lateral cervical spine radiograph based on the distance between the clavicle and mandible and the operative level; this was then applied to measurements on the patient's neck. Results. Procedures performed consisted of a mix of discectomy and fusion, disc replacement and combinations of both. The operative level ranged from C2-C3 to C7-T1, the most common being C5-C6. Twenty-three patients had a single-level, 26 a two level and 5 a three level procedure; all cases were performed through one single transverse incision. Conclusion. We describe the highly successful use of a straightforward method for accurate level transverse skin incision placement for cervical spine surgery In no case was it necessary to radically extend or to make a separate incision. There were no cases where the wrong level was operated on

Background: Desmoplastic fibroma (DF) of bone is a very infrequent non-metastasizing osseous tumour with local aggressive appearance. The tendency of local recurrence in published cases is high. Case reports: We present the clinical and radiological data of a male (35 years) and a female (37years) patient suffering from desmoplastic fibroma. Although in literature spinal lesions are severity rare, in our database two lesions located in the spine (C6 and L4) were identified. The first disturbances have been variable: The lesion in C6 was an accidental finding due to a control examination of a thyroid-ca, whereas the relapse-tumour of the L4 induced lumbago and hypaesthesia of the left heel. Due to the importance of the thyroid treatment it was decided to control the lesion in C6 in close intervals. The lumbar tumour was initially treated outside and the first relapse was marginal resected at our department 11 years after the first diagnosis. The bone alterations appeared radiographically lytic and cystic. Discussion: The spine is an unusual location of desmoplastic fibroma which arises in 56% at the long tubular bones followed by the mandible. To our knowledge only a few cases are reported to be located in the spine. DF located spinal, is a very untypical tumour and initial symptoms can be very unequal. Due to this dissimilar symptoms and variable histological appearance the diagnosis can be tricky. At least marginal resection should be achieved because intraleasional resected lesions show a local recurrence of 43%

Vascular anomalies with skeletal involvement are rare. To ameliorate diagnostics and therapy the classification of the International Society for the Study on Vascular Anomalies (ISSVA) should be applied where proliferating vascular tumours are separated from malformations, which are hereditary and do not change. Furthermore, blood and lymph vessel lesions are distinguished. In addition to isolated local or multifocal bone lesions, involvement of soft tissue and/or other organs can be observed. Here, we report on 6 patients with lymphangiomatosis. Diagnostic workup using whole body MRI is most sensitive to detect all lesions. Localisation was the mandible (n=2), spinal column (n=4), femur (n=1), tibia (n=1), pelvis (n=1), humerus (n=1), scapula (n=1) and rips (n=1). Soft tissue involvement was observed in all patients, 1 patient showed additional lesions in the kidney and spleen, 3 patients in the lung. These 3 patients could be diagnosed with Gorham’s disease, a potentially lethal form of skeletal lymphangiomatosis, with thoracic involvement. Next to the difficulty to find the correct diagnosis, therapy is not standardized. A major problem is the treatment of Gorham’s disease. In the literature, case reports on surgery as well as interferon alpha, chemotherapy, bisphosphonates and radiation therapy can be found. We performed surgery (n=2), radiotherapy (n= 1), polychemotherapy (n=1), bisphosphonates (n=2) and conservative therapy (n=3). One of the patients with Gorham’s disease died because of progressing pulmonary insufficiency. It is still unclear if prophylactic therapy for skeletal involvement should be administered and which therapy is effective. An international register and a multicenter clinical trial are urgently needed

Aims. Gene therapy research in the field of orthopaedics and traumatology have evolved during the last decade, leading to possible applications for the treatment of pathological conditions, such as bone fractures and cartilage defects. In particular, several gene transfer techniques have been employed so far for inducing bone formation in animal models of bone defects. Cell-based approaches, using in vitro and ex vivo genetically modified cells to be implanted in the animal, produced promising results as they enable the production of physiologic doses of an osteoinductive gene product into selected anatomical sites. In this study we used autologous skin fibroblasts, which are very simple to harvest and propagate in culture, transduced ex vivo with the new osteo-genic factor Lim Mineralization Factor-3 (Ad-LMP-3). These engineered cells produced successful bone healing when implanted by the use of a scaffold in rats, validating the in vivo osteoinductive properties of hLMP-3. Methods. Primary dermal fibroblasts cultures were established using a 1cm. 2. biopsy of shaved skin obtained from the abdomen of each rat after anesthesia. Semi-confluent primary fibroblasts were infected with either AdBMP-2 or AdhLMP-3 or both, using a overall multiplicity of infection (MOI) of 100 viral particles per cell. Cells transduced with Ad-eGFP at the same MOI were used as a viral infection control, while untreated cells served as a negative control. The transduced cells were harvested 24 hours after viral infection, resuspended in sterile PBS, let adsorbed on a Hydroxyapatite/Collagen scaffold and then implanted in a bone defect surgically performed in the mandible of immunocompetent rats. The animals were divided in 4 groups: 9 rats were treated with cells infected with AdLMP-3, 9 rats with cells infected with AdBMP-2 (positive controls), 9 rats with cells transduced with Ad-eGFP and 9 rats with untreated cells (controls). 3 Rats from each group were sacrified at 1, 2 and 3 months after the treatment and studied by x-rays, Micro-CT and histology (Von kossa and Alizarin staining). Results. All the animals treated with LMP-3 showed healing of the bone defect after 3 months, as confirmed his-tologically and radiographically. On the contrary none of the controls showed bone formation at latest time point. Conclusions. Recently, Lim Mineralization Proteins (LMP), coded by three different splice variants (LMP-1, LMP-2, LMP-3) of the same gene, have been identified as regulators of the osteoblast differentiation program. We have previously demonstrated that human LMP-3 (hLMP-3) contributes actively to bone formation, acting at least in part, through the BMP-2 signaling pathway, being capable of inducing differentiation of cells of mes-enchymal derivation towards the osteoblastic lineage, through the up-regulation of bone-specific genes, along with ectopic bone formation in vivo and mineralization in vitro. In this study we have analyzed the efficacy of an ex-vivo approach using autologous dermal fibroblasts infected with AdLMP-3. Engineered cells produced bone healing when implanted by the use of a scaffold in a rodent model, validating the in vivo osteoinductive properties of hLMP-3

Aims

Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate healing.

Aims

The aim of our study is to investigate the effect induced by alternated mechanical loading on Notch-1 in mandibular condylar cartilage (MCC) of growing rabbits.