Leukocyte-platelet rich fibrin on the treatment of a large paradental cyst: a novel regenerative approach.

Leukocyte-platelet rich fibrin (PRF) is an autologous biomaterial formed by platelets, cytokines, growth factors and cells imprisoned on a fibrin mesh, produced according to Choukroun's protocol. The aim of the present article was to report the use of PRF, associated with a bone substitute, on the regenerative treatment of a large bone defect resulting from the enucleation of a paradental cyst involving the posterior mandible. The treatment resulted in the maintenance of the bone volume, and radiographic evaluation showed new bone formation after 40 days, suggesting an osteogenic and osteoinductive effect. Also, the current literature was reviewed.

Local administration of HMGB-1 promotes bone regeneration on the critical-sized mandibular defects in rabbits.

Reconstruction of a critical-sized osseous defect is challenging in maxillofacial surgery. Despite novel treatments and advances in supportive therapies, severe complications including infection, nonunion, and malunion can still occur. Here, we aimed to assess the use of a beta-tricalcium phosphate (ß-TCP) scaffold loaded with high mobility group box-1 protein (HMGB-1) as a novel critical-sized bone defect treatment in rabbits. The study was performed on 15 specific pathogen-free New Zealand rabbits divided into three groups: Group A had an osseous defect filled with a ß-TCP scaffold loaded with phosphate-buffered saline (PBS) (100 µL/scaffold), the defect in group B was filled with recombinant human bone morphogenetic protein 2 (rhBMP-2) (10 µg/100 µL), and the defect in group C was loaded with HMGB-1 (10 µg/100 µL). Micro-computed tomography (CT) examination demonstrated that group C (HMGB-1) showed the highest new bone volume ratio, with a mean value of 66.5%, followed by the group B (rhBMP-2) (31.0%), and group A (Control) (7.1%). Histological examination of the HMGB-1 treated group showed a vast area covered by lamellar and woven bone surrounding the ß-TCP granule remnants. These results suggest that HMGB-1 could be an effective alternative molecule for bone regeneration in critical-sized mandibular bone defects.

Fractura patológica mandibular bilateral en osteonecrosis maxilar inducida por bisfosfonatos / Bilateral pathologic mandibular fracture in maxillary osteonecrosis induced by bisphosphonates

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The effect of platelet-rich fibrin exudate addition to porous poly(lactic-co-glycolic acid) scaffold in bone healing: An in vivo study.

Bone grafting procedures have been widely utilized as the current state-of-the-art for bone regeneration, with autogenous bone graft being the gold-standard bone reconstructive option. However, the use of autografts may be limited by secondary donor-site comorbidities, a finite amount of donor supply, increased operating time, and healthcare cost impact. Synthetic materials, or alloplasts, such as the polymeric material, poly(lactic-co-glycolic acid) (PLGA) has previously been utilized as a transient scaffold to support healing of bone defects with the potential to locally delivery osteogenic additives. In this study a novel procedure was adopted to incorporate both the dissolved contents and mechanical components of leukocyte- and platelet-rich fibrin (L-PRF) into an PLGA scaffold through a two-step method: (a) extraction of the L-PRF membrane transudate with subsequent immersion of the PLGA scaffold in transudate followed by (b) delivering a fibrin gel as a low-viscosity component that subsequently polymerizes into a highly viscous, gel-like biological material within the pores of the PLGA scaffold. Two, ~0.40 cm3 , submandibular defects (n = 24) were created per side using rotary instrumentation under continuous irrigation in six sheep. Each site received a PLGA scaffold (Intra-Lock R&D, Boca Raton, FL), with one positive control (without L-PRF exudate addition [nL-PRF]), and one experimental (augmented with PLGA/L-PRF Blocks [L-PRF]). Animals were euthanized 6 weeks postoperatively and mandibles retrieved, en bloc, for histological analysis. Histomorphometric evaluation for bone regeneration was evaluated as bone area fraction occupancy (BAFO) within the region of interest of the cortical bone (with specific image analysis software) and data presented as mean values with the corresponding 95% confidence interval values. Qualitative evaluation of nondecalcified histologic sections revealed extensive bone formation for both groups, with substantially more bone regeneration for the L-PRF induced group relative nL-PRF group. Quantitative BAFO within the defect as function of the effect of L-PRF exudate on bone regeneration, demonstrated significantly (p = .018) higher values for the L-PRF group (38.26% ± 8.5%) relative to the nL-PRF group (~28% ± 4.0%). This in vivo study indicated that L-PRF exudate has an impact on the regeneration of bone when incorporated with the PLGA scaffold in a large translational model. Further studies are warranted in order to evaluate the L-PRF exudate added, as well as exploring the preparation methods, in order to facilitate bone regeneration.

Quantifying Vascular Changes Surrounding Bone Regeneration in a Porcine Mandibular Defect Using Computed Tomography.

Angiogenesis is a critical process essential for optimal bone healing. Several in vitro and in vivo systems have been previously used to elucidate some of the mechanisms involved in the process of angiogenesis, and at the same time, to test potential therapeutic agents and bioactive factors that play important roles in neovascularization. Computed tomography (CT) is a noninvasive imaging technique that has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, such as bone formation within bony defects. Unfortunately, to date, angiogenesis evaluation relies primarily on histology, or ex vivo imaging and few studies have utilized CT to qualitatively and quantitatively study the vascular response during bone repair. In the current study a clinical CT-based technique was used to evaluate the effects of rhBMP-2 eluting graft treatment on soft tissue vascular architecture surrounding a large segmental bone defect model in the minipig mandible. The objective of this study was to demonstrate the efficacy of contrast-enhanced, clinical 64-slice CT technology in extracting quantitative metrics of vascular architecture over a 12-week period. The results of this study show that the presence of rhBMP-2 had a positive effect on vessel volume from 4 to 12 weeks, which was explained by a concurrent increase in vessel number, which was also significantly higher at 4 weeks for the rhBMP-2 treatment. More importantly, analysis of vessel architecture showed no changes throughout the duration of the study, indicating therapeutic safety. This study validates CT analysis as a relevant imaging method for quantitative and qualitative analysis of morphological characteristics of vascular tissue around a bone healing site. Also important, the study shows that CT technology can be used in large animal models and potentially be translated into clinical models for the development of improved methods to evaluate tissue healing and vascular adaptation processes over the course of therapy. This methodology has demonstrated sensitivity to tracking spatial and temporal changes in vascularization and has the potential to be applied to studying changes in other high-contrast tissues as well. Impact Statement Tissue engineering solutions depend on the surrounding tissue response to support regeneration. The inflammatory environment and surrounding vascular supply are critical to determining if therapies will survive, engraftment occurs, and native physiology is restored. This study for the first time evaluates the blood vessel network changes in surrounding soft tissue to a bone defect site in a large animal model, using clinically available computed tomography tools and model changes in vessel number, size, and architecture. While this study focuses on rhBMP2 delivery impacting surrounding vasculature, this validated method can be extended to studying the vascular network changes in other tissues as well.

Human Dental Pulp Stem Cells in Rat Mandibular Bone Defects.

This study aimed to evaluate the use of human dental pulp stem cells (hDPSCs) in non-critical-sized mandibular bone defects in rats. hDPSCs from permanent teeth were isolated and engrafted in mandibular bone defects in rats for 7, 14, and 28 days; bone defects without cells formed the control group. Samples were evaluated by scanning electron microscopy (SEM), light microscopy (hematoxylin and eosin staining), and the regeneration area was measured by the Image J program. Before surgery procedures, the human dental pulp cells were characterized as dental pulp stem cells: fusiform morphology, plastic-adherent; expression of CD105, CD73, and CD90; lack of expression of CD45 and CD34, and differentiated into osteoblasts, adipocytes, and chondroblasts. The results indicated that within 7 days the control group presented a pronounced bone formation when compared with the treated group (p < 0.05). After 14 days, the treated group showed an increase in bone formation, but with no statistical difference among the groups (p > 0.05). In the final evaluated period there was no difference between the control group and the treated group (p > 0.05). There was a significant difference between 7 and 14 days (p < 0.05) and between 7 and 28 days (p < 0.05) in the treated group. In conclusion, there is no evidence that the use of hDPSCs in the conditions of this study could improve bone formation in non-critical-sized mandibular bone defects.

Free Radical Production, Inflammation and Apoptosis in Patients Treated With Titanium Mandibular Fixations-An Observational Study.

Despite high biocompatibility of titanium and its alloys, this metal causes various side effects in the human body. It is believed that titanium biomaterials may induce an innate/adaptive immune response. However, still little is known about changes caused by titanium mandible implants, particularly with regard to bone healing. The latest studies showed disturbances in the antioxidant barrier, increased oxidative/nitrosative stress, as well as mitochondrial abnormalities in the periosteum covering titanium mandible fixations; nevertheless, the impact of titanium implants on free radical production, inflammation, and mandible apoptosis are still unknown. Because severe inflammation and apoptosis are among the main factors responsible for disturbances in osteointegration as well as implant rejection, this study is the first to evaluate pro-oxidant enzymes, cytokines as well as pro- and anti-apoptotic proteins in the periosteum of patients with a broken jaw, treated with titanium miniplates and miniscrews. The study group consisted of 29 patients with double-sided fracture of the mandible body requiring surgical treatment. We found significantly higher activity of NADPH oxidase and xanthine oxidase as well as enhanced rate of free radical production in the periosteum of patients in the study group compared to the control group. The markers of inflammation [interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), transforming growth factor ß (TGF-ß) and ß-glucuronidase (GLU)] as well as apoptosis [Bax, Bax/Bcl-2 ratio, caspase-3 (CAS-3) and nitric oxide (NO)] were significantly elevated in periosteum covering titanium fixations compared to the control group. In the study group, we also demonstrated an increased content of titanium on the periosteum surface, which positively correlated with CAS-3 activity. The study led us to the conclusion that titanium mandible implants increase the production of pro-inflammatory cytokines, and enhance free radical generation in the periosteum covering titanium miniplates and miniscrews. Additionally, exposure to Ti6Al4V titanium alloy induces apoptosis in the mandible periosteum. However, no clinical signs of the said phenomena have been observed.

Sandwich-Like Nanofibrous Scaffolds for Bone Tissue Regeneration.

Advanced bone healing approaches included a wide range of biomaterials that mainly mimic the composition, structure, and properties of bone extracellular matrix with osteogenic activity. The present study aimed to develop a sandwich-like structure of electrospun nanofibers (NFs) based on polycaprolactone (PCL) and chitosan/polyethylene oxide (CS/PEO) composite to stimulate bone fracture healing. The morphology of the fabricated scaffolds was examined using scanning electron microscopy (SEM). Apatite deposition was evaluated using simulated body fluid (SBF). The physicochemical and mechanical properties of samples were analyzed by Fourier transform infrared, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and universal testing machine. SEM images exhibited a porous three-dimensional structure with NF diameters of 514-4745 nm and 68-786 nm for PCL NFs layer and the sandwich-like NFs scaffolds, respectively. Deposition of apatite crystal on scaffolds started at week 2 followed by heavy deposition at week 8. This was confirmed by measuring the consumption of calcium and phosphorous ions from SBF. Thermal stability of scaffolds was confirmed using DSC and TGA. Moreover, the PCL NF layer in the middle of the developed sandwich structure reinforced the scaffolds with bear load up to 12.224 ± 1.12 MPa and Young's modulus of 17.53 ± 3.24 MPa. The scaffolds' porous structure enhanced both cell propagation and proliferation. Besides, the presence of CS in the outer NF layers of the scaffolds increased the hydrophilicity, as evidenced by the reduction of contact angle from 116.6 to 57.6°, which is essential for cell attachment. Cell viability study on mesenchymal stem cells proved the cytocompatibility of the fabricated scaffolds. Finally, in vivo mandibular bone defect rabbit model was used to confirm the regeneration of a new healthy bone within 28 days. In conclusion, the developed scaffolds could be a promising solution to stimulate bone regeneration.

Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone.

BACKGROUND: Autologous bone grafts remain a standard of care for the reconstruction of large bony defects, but limitations persist. The authors explored the bone regenerative capacity of customized, three-dimensionally printed bioactive ceramic scaffolds with dipyridamole, an adenosine A2A receptor indirect agonist known to enhance bone formation. METHODS: Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits (n = 15). Defects were replaced by a custom-to-defect, three-dimensionally printed bioactive ceramic scaffold composed of ß-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 µM dipyridamole. At 8 weeks, animals were euthanized and the rami retrieved. Bone growth was assessed exclusively within scaffold pores, and evaluated by micro-computed tomography/advanced reconstruction software. Micro-computed tomographic quantification was calculated. Nondecalcified histology was performed. A general linear mixed model was performed to compare group means and 95 percent confidence intervals. RESULTS: Qualitative analysis did not show an inflammatory response. The control and collagen groups (12.3 ± 8.3 percent and 6.9 ± 8.3 percent bone occupancy of free space, respectively) had less bone growth, whereas the most bone growth was in the dipyridamole group (26.9 ± 10.7 percent); the difference was statistically significant (dipyridamole versus control, p < 0.03; dipyridamole versus collagen, p < 0.01 ). There was significantly more residual scaffold material for the collagen group relative to the dipyridamole group (p < 0.015), whereas the control group presented intermediate values (nonsignificant relative to both collagen and dipyridamole). Highly cellular and vascularized intramembranous-like bone healing was observed in all groups. CONCLUSION: Dipyridamole significantly increased the three-dimensionally printed bioactive ceramic scaffold's ability to regenerate bone in a thin bone defect environment.

Biomaterials-aided mandibular reconstruction using in vivo bioreactors.

Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves suitable for their own specific anatomical pathology. The in vivo bioreactor strategy facilitates the generation of large autologous vascularized bony tissue of customized geometry without the addition of exogenous growth factors or cells. To translate this technology, we investigated its success in reconstructing a mandibular defect of physiologically relevant size in sheep. We fabricated and implanted 3D-printed in vivo bioreactors against rib periosteum and utilized biomaterial-based space maintenance to preserve the native anatomical mandibular structure in the defect site before reconstruction. Nine weeks after bioreactor implantation, the ovine mandibles were repaired with the autologous bony tissue generated from the in vivo bioreactors. We evaluated tissues generated in bioreactors by radiographic, histological, mechanical, and biomolecular assays and repaired mandibles by radiographic and histological assays. Biomaterial-aided mandibular reconstruction was successful in a large superior marginal defect in five of six (83%) sheep. Given that these studies utilized clinically available biomaterials, such as bone cement and ceramic particles, this strategy is designed for rapid human translation to improve outcomes in patients with large mandibular defects.

Localized low-dose rhBMP-2 is effective at promoting bone regeneration in mandibular segmental defects.

At least 26% of recent battlefield injuries are to the craniomaxillofacial (CMF) region. Recombinant human bone morphogenetic protein 2 (rhBMP-2) is used to treat CMF open fractures, but several complications have been associated with its use. This study tested the efficacy and safety of a lower (30% recommended) dose of rhBMP-2 to treat mandibular fractures. rhBMP-2 delivered via a polyurethane (PUR) and hydroxyapatite/ß-tricalcium phosphate (Mastergraft®) scaffold was evaluated in a 2 cm segmental mandibular defect in minipigs. Bone regeneration was analyzed at 4, 8, and 12 weeks postsurgery using clinical computed tomography (CT) and rhBMP-2, and inflammatory marker concentrations were analyzed in serum and surgery-site drain effluent. CT scans revealed that pigs treated with PUR-Mastergraft® + rhBMP-2 had complete bone bridging, while the negative control group showed incomplete bone-bridging (n = 6). Volumetric analysis of regenerated bone showed that the PUR-Mastergraft® + rhBMP-2 treatment generated significantly more bone than control by 4 weeks, a trend that continued through 12 weeks. Variations in inflammatory analytes were detected in drain effluent samples and saliva but not in serum, suggesting a localized healing response. Importantly, the rhBMP-2 group did not exhibit an excessive increase in inflammatory analytes compared to control. Treatment with low-dose rhBMP-2 increases bone regeneration capacity in pigs with mandibular continuity defects and restores bone quality. Negative complications from rhBMP-2, such as excessive inflammatory analyte levels, were not observed. Together, these results suggest that treatment with low-dose rhBMP-2 is efficacious and may improve safety when treating CMF open fractures. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1491-1503, 2019.

Reconstruction of mandibular bone defects using biphasic calcium phosphate bone substitutes with simultaneous implant placement in mini-swine: A pilot in vivo study.

This study aimed to investigate implant osseointegration using a new strategy of biphasic calcium phosphate (BCP) bone substitutes with simultaneous implant placement in mandibular reconstruction. Additionally, the temporal transcriptional profile associated with the early biological processes during osseointegration was determined. BCP and hydroxyapatite (HA) bone substitutes with simultaneous implant placement were grafted into mandibular defects created in mini-swine. Radiographic, histological, and biochemical analyses were applied for evaluation of osseointegration effects at 4 months after the grafting procedure. Bone formation around the implant was assessed by the bone area percentage (BA%) and the bone-implant-contact percentage (BIC%). The biomechanical evaluation was performed by the implant pullout test and the removal torque test. Microarray technology was utilized for gene expression comparison analysis at day 14 postoperatively. Radiographic and histological observation indicated enhanced bone formation in the BCP group compared to the HA group. Histomorphometric analyses of BA% and BIC% as well as biochemical analyses of the maximal pull-out force and the ultimate shear strength were all significantly greater in the BCP group (p < 0.05). Transcriptional analysis at an early stage of osseointegration revealed that genes belonging to biological processes associated with cell proliferation, development, osteogenesis, angiogenesis, and neurogenesis as well as the osteogenesis-related TGF-ß/BMP and WNT signaling pathways were upregulated in the BCP group. In conclusion, the reconstruction of mandibular defects using BCP with simultaneous implant placement resulted in superior osseointegration effects. A number of candidate genes that were differentially expressed may contribute to the superior osseointegration effects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2071-2079, 2019.

Hydroxyapatite nanowires modified polylactic acid membrane plays barrier/osteoinduction dual roles and promotes bone regeneration in a rat mandible defect model.

Periodontitis is an inflammatory disease leading to tooth loss, alveolar bone absorption and disorder of masticatory function. Guided tissue regeneration (GTR) is one of the most common strategies for regeneration of lost periodontium. During surgical process, barrier membranes, and osteoinductive/osteoconductive materials should be placed, respectively, which may increase risks of infection, bleeding, and difficulty of operation. Here, we introduced a new kind of hydroxyapatite (HAp) nanowires modified polylactic acid (PLA) membrane to achieve barrier/osteoinduction dual functions. The physicochemical property measurements suggested the two sides of the composite membrane did not change after composition. Then a rat mandibular defect model was established to investigate barrier and osteoinductive effects of this composite membrane. After implantation, effects of functional cells engraftment and osteoinduction were detected by scanning electron microscope (SEM), histomorphometric measurement, immunohistochemical staining, and Micro-CT scanning. SEM images showed HAp side engrafted more cells than PLA side. The result of immunohistochemical staining suggested HAp/PLA promoted the expression of bone-related markers. Moreover, there were more newly formed bones with better quality in HAp/PLA group. Therefore, this composite membrane would be a promising biomaterial in tissue engineering for bone regeneration due to its barrier/osteoinduction dual functions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3099-3110, 2018.

Functional reconstruction of critical-sized load-bearing bone defects using a Sclerostin-targeting miR-210-3p-based construct to enhance osteogenic activity.

A considerable amount of research has focused on improving regenerative therapy strategies for repairing defects in load-bearing bones. The enhancement of tissue regeneration with microRNAs (miRNAs) is being developed because miRNAs can simultaneously regulate multiple signaling pathways in an endogenous manner. In this study, we developed a miR-210-based bone repair strategy. We identified a miRNA (miR-210-3p) that can simultaneously up-regulate the expression of multiple key osteogenic genes in vitro. This process resulted in enhanced bone formation in a subcutaneous mouse model with a miR-210-3p/poly-l-lactic acid (PLLA)/bone marrow-derived stem cell (BMSC) construct. Furthermore, we constructed a model of critical-sized load-bearing bone defects and implanted a miR-210-3p/ß-tricalcium phosphate (ß-TCP)/bone mesenchymal stem cell (BMSC) construct into the defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. We also identified a new mechanism by which miR-210-3p regulates Sclerostin protein levels. This miRNA-based strategy may yield novel therapeutic methods for the treatment of regenerative defects in vital load-bearing bones by utilizing miRNA therapy for tissue engineering. STATEMENT OF SIGNIFICANCE: The destroyed maxillofacial bone reconstruction is still a real challenge for maxillofacial surgeon, due to that functional bone reconstruction involved load-bearing. Base on the above problem, this paper developed a novel miR-210-3p/ß-tricalcium phosphate (TCP)/bone marrow-derived stem cell (BMSC) construct (miR-210-3p/ß-TCP/BMSCs), which lead to functional reconstruction of critical-size mandible bone defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. In addition, we also found the mechanism of how the delivered microRNA activated the signaling pathways of endogenous stem cells, leading to the defect regeneration. This miRNA-based strategy can be used to regenerate defects in vital load-bearing bones, thus addressing a critical challenge in regenerative medicine by utilizing miRNA therapy for tissue engineering.

New approach for vertical bone regeneration using in situ gelling and sustained BMP-2 releasing poly(phosphazene) hydrogel system on peri-implant site with critical defect in a canine model.

An injectable hydrogel system with sustained bone morphogenetic protein 2 (BMP-2) release ability was developed for vertical bone regeneration at peri-implant sites and enhanced osseointegration of dental implants. In three young male beagle dogs, a pair of defects was created on both sides of the mandibular bone. Next, two implants were transplanted into each defect. In situ gelling polymer solutions with or without BMP-2 were applied to cover the implants and mandibular defects. The effects of the in situ gelling and sustained BMP-2 releasing (IGSR) hydrogel system on peri-implant bone regeneration were evaluated by radiologic examination, micro-computed tomography, and histomorphometric analysis. Twelve weeks after the treatment, significant bone generation at the peri-implant site occurred following BMP-2/IGSR hydrogel treatment. Bone volume and mineral density were increased by 1.7- and 1.3-fold, respectively (p < 0.01 and 0.05 vs. control, respectively) for the BMP-2/IGSR hydrogel system. And, 0.57-0.31 mm vertical bone generation was observed at the peri-implant site for the BMP-2/IGSR hydrogel system, while rare vertical bone generation occurred in the control group. The BMP-2/IGSR hydrogel system significantly increased bone to implant contact % between induced bone and existing bone (p < 0.05 and 0.01 vs. control). These vertical bone regeneration and higher osseointegration levels demonstrated the effectiveness of the BMP-2/IGSR hydrogel system. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 751-759, 2018.

Osteoinductive porous biphasic calcium phosphate ceramic as an alternative to autogenous bone grafting in the treatment of mandibular bone critical-size defects.

The bone-induction capacity of a porous biphasic calcium phosphate (pBCP) using heterotopic implantation in mouse (mHI-model) and its efficacy as substitute for autograft in mandibular critical-size defect in rabbit (rabMCSD-model) was investigated. In mHI-model, pBCP was implanted into the thigh muscles and bone formation was histomorphometrically and immunohistochemically evaluated. In rabMCSD-model, 13 mm bone defects were treated with pBCP or autograft and bone repair comparatively evaluated by radiographic and histomorphometric methods. In mHI-model, formed bone and immunolabeling for bone morphogenetic protein-2 and osteopontin were observed in 90% of pBCP implanted samples after 12 weeks. In rabMCSD-model neither statistically significant difference was found in newly formed bone between pBCP and autograft groups at 4 weeks (18.8 ± 5.5% vs 27.1 ± 5.6%), 8 weeks (22.3 ± 2.7% vs 26.2 ± 5.1), and 12 weeks (19.6 ± 4.7% vs 19.6 ± 2.3%). At 12 weeks, the stability and contour of the mandible were restored in both treatments. Near tooth remaining, pBCP particles were covered by small amount of mineralized tissue exhibiting perpendicular attachments of collagen fiber bundles with histological characteristic of acellular cementum. Within the limitations of this study, it was concluded that pBCP is osteoinductive and able to stimulate the new formation of bone and cementum-like tissues in rabMCSD-model, suggesting that it may be an alternative to treatment of large bone defect and in periodontal regenerative therapy. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1546-1557, 2018.

Effects of rhBMP-2 Loaded Titanium Reinforced Collagen Membranes on Horizontal Bone Augmentation in Dogs.

The aim of this study was to evaluate the efficacy of growth factor loaded collagen membranes on new bone formation during horizontal bone augmentation. Mandibular defects (4 × 4 × 4 mm) were surgically prepared in six male beagle dogs, which were then protected with one of three types of membranes: (1) titanium mesh, (2) titanium reinforced collagen, or (3) rhBMP-2 loaded titanium reinforced collagen. Animals were euthanized 8 and 16 weeks after surgery, and nondecalcified specimens were prepared and histomorphologically investigated to determine the degree of osteogenesis. Data were analyzed with Friedman test. With respect to the degree of osteogenesis at earlier stage (8 weeks after surgery), there was significantly higher new bone ratio in rhBMP-2 loaded membrane group (p > 0.05). However, with respect to the long-term results (16 weeks after surgery), there were no significant differences among the three membranes (p > 0.05). Based on histomorphometric analysis, there were no significant differences in horizontal bone gaining ratio (p > 0.05).

Retrospective analysis of jaw biopsies in young adults. A study of 1599 cases in Southern Brazil

Background: To evaluate the prevalence and the characteristics of jaw lesions diagnosed in young adults aged 20 to 30 years in a southern Brazil reference center, over a period of 25 years. And to analyze the concordance between clinical and histological diagnosis. Material and Methods: In this cross-sectional retrospective study, the biopsies files from this center were retrieved and data regarding sex, age, bone localization, clinical and histological diagnosis were collected. The histological diagnosis were grouped into the categories Cystic lesions of odontogenic origin, Periapical inflammation, Odontogenic tumors, Bone diseases, Health tissue and Nonspecific diagnostic. Absolute and relative frequencies were estimated with descriptive analysis. The agreement between clinical and histological diagnosis was measured through Kappa statistic. Results: A total of 18,181 histopathological analysis were performed during the period of the study, registering 1,599 jaw lesions in young adults. The average age of individuals was 24,59 years (SD 3,1). Nine hundred ninety-one (62%) lesions were found in females and 608 (38%) in males. More than half of pathologies were cystic lesions of odontogenic origin (822/51.4%), followed by periapical inflammation (282/17.6%). Regarding the site of lesions, more than half occurred in posterior mandible (877/54.8%), followed by posterior maxilla (339/21.2%). The most frequent entities were periapical cyst, chronic periapical granuloma, dental follicle and paradental cyst, corresponding to a total of 1,202 (75.2%) evaluated cases. In relation to the analysis of concordance between clinical and histological diagnosis the general Kappa index was 0.5, which is considered moderate. Finally, the findings confirm data from literature about the most frequent jaw pathologies in young adults and serve as aid for preventive measures of some entities. Additionally, they can improve the formulation of differential diagnosis and the patient management (AU)

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Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2.

Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics.

Computational Approach to Identify Different Injuries by Firearms.

Complications arise in the analysis of gunshot wounds to the maxillofacial region, when neither the projectile nor the gun is found at the crime scene. We simulated 5- and 15-cm firing distances at a human mandible to investigate the external morphology of entrance wounds based on fire range. The ammunition models, .40-caliber S&W, .380-caliber, and 9 × 19-mm Luger, were constructed with free-form NURBS surfaces. In a dynamic simulation, projectiles were fired against mandibular body 3D model at 5 and 15 cm. All entrance wounds presented oval aspect. Maximum diameter and von Mises stress values were 16.5 mm and 50.8 MPa, both for .40-caliber S&W fired at 5 cm. The maximum energy loss was 138.4 J for .40 S&W fired at 15 cm. In conclusion, the mandible was most affected by .40-caliber S&W and morphological differences were observable in holes caused by different incoming projectile calibers fired at different distances.