Anatomic study of the position of the mandibular canal and corresponding mandibular third molar on cone-beam computed tomography images.

PURPOSE: The positional relationship between the mandibular canal and corresponding third molars is a key anatomic factor of inferior alveolar nerve (IAN) injury. The aim of the present study is to classify the anatomic three-dimensional relationship between the mandibular third molar and the mandibular canal on cone-beam computed tomography (CBCT) images. METHODS: This study used CBCT images to classify the positional relationship between the mandibular canal and corresponding third molars. CBCT images of 749 patients (1296 mandibular third molars) were analyzed to draw up a classification. RESULTS: On a total of 1296 third molars, the mandibular canal relative to the roots of the mandibular third molar was on the apical side (88.1%), followed by the buccal side (7.9%), the lingual side (3.5%), and then between the roots (0.5%). Ninety-five (7.1%) third molars had a close relation with the mandibular canal, while 1201 (92.7%) third molars had no direct contact. The percentage of the mandibular canal contacts with the mandibular third molar was higher when the mandibular canal was lingually positioned. CONCLUSIONS: The anatomic structures of the mandibular third molar and the mandibular canal may be helpful to make adequate surgical planning to avoid or reduce nerve involvement.

Focal adhesion kinase knockdown in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis via downregulating MCP-1/CCL2 expression.

Carcinoma-associated fibroblasts (CAFs) have been demonstrated to play an important role in the occurrence and development of oral squamous cell carcinoma (OSCC). The aim of this study is to investigate the influence of CAFs on OSCC cells and to explore the role of focal adhesion kinase (FAK) in this process. The results showed that oral CAFs expressed a higher level of FAK than normal human gingival fibroblasts (HGFs), and the conditioned medium (CM) of CAFs could induce the invasion and migration of SCC-25, one oral squamous carcinoma cell line. However, knockdown of FAK by small interfering RNA (siRNA) resulted in inhibition of CAF-CM induced cell invasion and migration in SCC-25, probably by reducing the production of monocyte chemoattractant protein-1 (MCP-1/CCL2), one of downstream target chemokines. Therefore, our findings indicated that targeting FAK in CAFs might be a promising strategy for the treatment of OSCC in the future.

Distal-less homeobox 2 promotes the osteogenic differentiation potential of stem cells from apical papilla.

Dental tissue-derived mesenchymal stem cells (MSCs) are a reliable cell source for dental tissue regeneration. However, the molecular mechanisms underlying the directed differentiation of MSCs remain unclear; thus, their use is limited. The histone demethylase, lysine (K)-specific demethylase 4B (KDM4B), plays critical roles in the osteogenic commitment of MSCs by up-regulating distal-less homeobox 2 (DLX2) expression. The DLX2 gene is highly expressed in dental tissue-derived MSCs but the roles of DLX2 in osteogenesis are unclear. Here, we investigate DLX2 function in stem cells from apical papilla (SCAPs). We found that, in vitro, DLX2 expression was up-regulated in SCAPs by adding BMP4 and by inducing osteogenesis. The knock-down of DLX2 in SCAPs decreased alkaline phosphatase (ALP) activity and mineralization. DLX2 depletion affected the mRNA expression of ALP, bone sialoprotein (BSP) and osteocalcin (OCN) and inhibited SCAP osteogenic differentiation in vitro. Over-expression of DLX2 enhanced ALP activity, mineralization and the expression of ALP, BSP and OCN in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis was triggered when DLX2 was activated. Furthermore, DLX2 expression led to the expression of the key transcription factor, osterix (OSX) but not to the expression of runt-related transcription factor 2 (RUNX2). Taken together, these results indicate that DLX2 is stimulated by BMP signaling and enhances SCAP osteogenic differentiation by up-regulating OSX. Thus, the activation of DLX2 signaling might improve tissue regeneration mediated by MSCs of dental origin. These results provide insight into the mechanism underlying the directed differentiation of MSCs of dental origin.

Periodontal ligament stem cells regulate B lymphocyte function via programmed cell death protein 1.

Periodontal ligament stem cells (PDLSCs) have provided novel cell sources for tooth and periodontal tissue regeneration. Allogeneic PDLSCs can reconstruct periodontal ligament tissue that has been damaged by periodontal diseases and regulate T-cell immunity. However, the effect of PDLSCs on B cells remains unknown. Here, we treated periodontitis in a miniature pig model using allogeneic PDLSCs and showed a reduction in humoral immunity in the animals. When cocultured with normal B cells, human PDLSCs (hPDLSCs) had similar effects as bone marrow mesenchymal stem cells in suppressing B cell proliferation, differentiation, and migration, while intriguingly, hPDLSCs increased B cell viability by secreting interleukin-6. Mechanistically, hPDLSCs suppressed B cell activation through cell-to-cell contact mostly mediated by programmed cell death protein 1 and programmed cell death 1 ligand 1. Our data revealed a previously unrecognized function of PDLSCs in regulating humoral immune responses, which may represent a novel therapeutic strategy for immune-related disorders.

Osteoblastoma of the maxilla: A case report and review of the literature.

Osteoblastoma is a benign tumour with aggressive trait usually seen in young males between 10 and 40 years of age. This condition is quite rare in children. Here, we report one such rare osteoblastoma occurring in the maxilla of a 4-year-old boy and discuss the clinical presentation, radiologic and histologic features, and treatment of this patient, and a brief review.

Chemotherapeutics-induced osteonecrosis of the jaw in a patient with acute promyelocytic leukemia: A rare case report.

Medication related osteonecrosis of the jaw (MRONJ) is a commonly observed adverse reaction after taking anti-resorption and anti-angiogenic drugs. As we all know, arsenic compounds are used as drugs for pulp devitalization therapy and its local diffusion can cause osteonecrosis. As the treatment of leukemia, the medical records of osteonecrosis are rarely reported. Arsenic compounds may be a potential risk factor for osteonecrosis, which should be brought to the attention of dentists.

Osteogenesis Performance of Boronized Ti6Al4V/HA Composites Prepared by Microwave Sintering: In Vitro and In Vivo Studies.

The boronized Ti6Al4V/HA composite is deemed to be an important biomaterial because of its potential remarkable mechanical and biological properties. This paper reports the osteogenesis performance of the boronized Ti6Al4V/HA composite, which was prepared by microwave sintering of powders of Ti6Al4V, hydroxyapatite (HA), and TiB2 in high-purity Ar gas at 1050 °C for 30 min, as dental implant based on both cell experiments in vitro and animal experiments in vivo. The comparison between the boronized Ti6Al4V/HA composite and Ti, Ti6Al4V, and boronized Ti6Al4V in the terms of adhesion, proliferation, alkaline phosphate (ALP) activity, and mineralization of MG-63 cells on their surfaces confirmed that the composite exhibited the best inductive osteogenesis potential. It exerted a more significant effect on promoting the early osteogenic differentiation of osteoblasts and exhibited the maximum optical density (OD) value in the MTT assay and the highest levels of ALP activity and mineralization ability, primarily ascribed to its bioactive HA component, porous structure, and relatively rough micro-morphology. The in vivo study in rabbits based on the micro-computed tomography (micro-CT) analysis, histological and histomorphometric evaluation, and biomechanical testing further confirmed that the boronized Ti6Al4V/HA composite had the highest new bone formation potential and the best osseointegration property after implantation for up to 12 weeks, mainly revealed by the measured values of bone volume fraction, bone implant contact, and maximum push-out force which, for example, reached 48.64%, 61%, and 150.3 ± 6.07 N at the 12th week. Owing to these inspiring features, it can serve as a highly promising dental implant.

[Rat model with oral submucous fibrosis induced by arecoline and mechanical stimulation].

OBJECTIVE: The aim of this study was to induce oral submucous fibrosis (OSF) in Sprague-Dawley(SD) rat models by arecoline and mechanical stimulation. METHODS: Two factors factorial design was used to divide 48 rats into 8 groups (n=6). Different concentrations of arecoline (0, 0.5, 2, and 8 mg·mL⁻¹) and mechanical stimulation (with or without brush) were treated. After 16 weeks of treatment, the mouth opening was measured, the pathological changes of the buccal mucosa were observed, and the expressions of type Ⅲ collagen, transforming growth factor ß1 (TGF-ß1), and interferon-γ (IFN-γ) were detected. RESULTS: In rats with moderate and high concentrations of arecoline, typical OSF pathological features were observed in the buccal mucosa, the mouth openings were significantly reduced, and the expression levels of type Ⅲ colla-gen and TGF-ß1 were significantly increased (P<0.05). Although mechanical stimulation can increase the three indexes of mucosa (P<0.05), no pathological change and difference in the mouth opening was observed (P>0.05). CONCLUSIONS: Moderate and high concentrations of arecoline can induce OSF in SD rats, but mechanical stimulation cannot induce OSF.

Human dental pulp stem cells regulate allogeneic NK cells' function via induction of anti-inflammatory purinergic signalling in activated NK cells.

OBJECTIVES: Mesenchymal stem cells (MSCs) could regulate the function of various immune cells. It remains unclear whether MSCs additionally possess immunostimulatory properties. We investigated the impact of human MSCs on the responsiveness of primary natural killer (NK) cells in terms of induction of anti-inflammatory purinergic signalling. MATERIAL AND METHODS: We obtained human bone marrow mesenchymal stem cells (BMMSCs) and dental pulp stem cells (DPSCs). NK cells were isolated from peripheral blood of healthy volunteers. Activated NK cells were cultured with MSCs. Proliferation assay, apoptosis analysis, activating or inhibitory receptor expression and degranulation assay were used to explore NK cells' function. High-performance liquid chromatography was used to investigate the purinergic signalling in activated NK cells. RESULTS: Both DPSCs and BMMSCs could impair proliferation and promote apoptosis of activated NK cells. Also, activated NK cells could cause DPSCs to lyse. Furthermore, the expression of activating NK cells' receptors was decreased, but inhibitory receptors of NK cells were elevated following co-cultivation. NK cells acquired CD73 expression, while MSCs could release ATP into the extracellular space where nucleotides were converted into adenosine (ADO) following co-culture system. Under the existence of exogenous 2-chloroadenosine (CADO), the cytotoxic capacity of NK cells was remarkably depressed in a concentration-dependent manner. CONCLUSIONS: DPSCs and BMMSCs could depress NK cells' function by hydrolysing ATP to ADO using CD39 and CD73 enzymatic activity. Our data suggested that DPSCs might represent a new strategy for treating immune-related diseases by regulating previously unrecognized functions in innate immune responses.

Electroactive BaTiO3 nanoparticle-functionalized fibrous scaffolds enhance osteogenic differentiation of mesenchymal stem cells.

It has been proven that the surface topographic cues of fiber arrangement can induce osteogenic differentiation of mesenchymal stem cells. However, this effect alone is weak and insufficient to meet the needs of regenerative medicine. In this work, electroactivity concept was introduced to enhance the osteoinductivity of fibrous scaffolds. The randomly oriented and aligned electroactive fibrous scaffolds of poly-(l-lactic acid) (PLLA) with incorporation of ferroelectric ceramic BaTiO3 (BTO) nanoparticles (NPs) were fabricated by electrospinning. Physicochemical properties, including fiber morphology, microstructure, composition, thermal stability, surface roughness, and surface wettability, of these fibrous scaffolds were studied. The dielectric properties of the scaffolds were evaluated. The results showed that the randomly oriented BTO/PLLA composite fibrous scaffolds had the highest dielectric permittivity of 1.19, which is of the same order of magnitude as the natural bone. The combined effects of fiber orientation and electrical activity on the osteogenic responses of bone marrow mesenchymal stem cells (BM-MSCs) were specifically investigated. Randomly oriented composite fibrous scaffolds significantly promoted polygonal spreading and encouraged early osteogenic differentiation in BM-MSCs, whereas aligned composite fibrous scaffolds promoted cell elongation and discouraged osteogenic differentiation. These results evidenced that randomly fiber orientation and biomimetic electric activity have combining effects on osteogenic differentiation of BM-MSCs. Our findings indicate that coupling effects of multi-physical properties should be paid more attention to mimic the microenvironment for enhancing osteogenic differentiation of BM-MSCs.

Rapid prototyping-assisted maxillofacial reconstruction.

Rapid prototyping (RP) technologies have found many uses in dentistry, and especially oral and maxillofacial surgery, due to its ability to promote product development while at the same time reducing cost and depositing a part of any degree of complexity theoretically. This paper provides an overview of RP technologies for maxillofacial reconstruction covering both fundamentals and applications of the technologies. Key fundamentals of RP technologies involving the history, characteristics, and principles are reviewed. A number of RP applications to the main fields of oral and maxillofacial surgery, including restoration of maxillofacial deformities and defects, reduction of functional bone tissues, correction of dento-maxillofacial deformities, and fabrication of maxillofacial prostheses, are discussed. The most remarkable challenges for development of RP-assisted maxillofacial surgery and promising solutions are also elaborated.

A comparative study of the influence of three pure titanium plates with different micro- and nanotopographic surfaces on preosteoblast behaviors.

There is a great demand for dental implants with the ability to accelerate periimplant bone regeneration. Modification of surface micro- and nanotopographies has been revealed to affect bone cell metabolism. In this study, we utilized dielectric barrier discharge (DBD) technology to modify commercially pure titanium (Ti-tr) surfaces and then investigated the cytocompability of DBD-modified Ti surface when compared with machined (Ti-m) and polished (Ti-p) Ti surfaces. These three kinds of Ti plates exhibited different surface energies and topographies at the micro- and nanoscale levels. The DBD-treated pure Ti surface significantly enhances cell adhesion, spread, and proliferation of MC3T3-E1 preosteoblast cells compared with the Ti-p and Ti-m surfaces, suggesting that Ti-tr has better cytocompatibility compared with the other two surfaces. Preosteoblast cells on Ti-m surface exhibited higher alkaline phosphatase activity than cells on Ti-tr and Ti-p surfaces 14 days after seeding. No significant difference in alkaline phosphatase activity was observed between cells grown on Ti-tr and Ti-p surfaces. Our study demonstrated that DBD modification significantly enhanced cell adhesion, spread, and proliferation of preosteoblasts with no negative effects on cell differentiation. Microtopography and nanotopography of the surfaces of different materials and chemical/energetic properties have a synergistic effect on cell attachment, proliferation, and differentiation.

[Clinical application of heterogeneous acellular dermal matrix in the surgical treatment of oral submucous fibrosis].

PURPOSE: The aim of this study was to evaluate the clinical effect of heterogeneous acellular dermal matrix in the surgical treatment of advanced oral submucous fibrosis (OSF). METHODS: There were eight patients who had undergone surgical treatment of trismus caused by OSF. Surgery was performed under general anaesthesia given through a nasoendotracheal tube using a fibreoptic bronchoscope. All the fibrous bands on the buccal mucosa were incised and bluntly dissected to stretch the mouth opening. Based on the defect, heterogeneous acellular dermal matrix graft was applied directly on the bilateral wounds. A tie-over dressing technique was used to hold the graft firmly to its bed.The sutures and dressing material were removed on the tenth to fourteenth day after the operation. All the patients were asked to stretch the mouth opening 3 times daily and were followed up for at least 6 months. A modality of medical treatment including multiple micronutrient supplements and steroid injection therapy were carried out if necessary. The changes in the interincisal distances (IDs) were analyzed in the preoperative, intraoperative, and postoperative stages. The data was analyzed with SPSS16.0 software package for one-way ANOVA. RESULTS: The overall success rate was 100% without any or only partial graft loss. There were no immunologic reactions or significant complications.The mean preoperative, intraoperative, and final follow-up interincisal distances were 12.04, 35.46, and 29.33 mm, respectively. Evaluation of the changes in the IDs revealed statistically significant differences between the values recorded at the different stages.(P<0.05). CONCLUSIONS: Heterogeneous acellular dermal matrix may be a valuable biomaterial for repairing oral mucosal defects after surgery on the fibrous bands in patients with advanced OSF through covering and protecting wound surface early,which shortens the healing time of wound, decreases relapse of fibrosis and improve the restricted mouth opening.

[Reconstruction of oral and maxillofacial defects using free anterolateral thigh flaps in patients with malignant tumors].

PURPOSE: To explore the value of free anterolateral thigh flaps in the reconstruction of oral and maxillofacial defects following radical resection of malignant tumors. METHODS: Seventy-six cases of oral and maxillofacial malignant tumor from December 2007 to June 2009, including 32 tongue carcinomas, 16 buccal carcinomas, 10 carcinomas of floor of mouth, 9 gingival carcinomas, 8 oropharyngeal carcinomas and 1 skin carcinoma, underwent radical resection. Free anterolateral thigh flaps were used to reconstruct the defects. The postoperative effect and flap success rate were evaluated. RESULTS: Among 76 cases, 74 flaps survived completely with satisfied configuration, only 2 flaps had complete necrosis. The survival rate was 97.3%. No complications were observed in the donor site. CONCLUSIONS: The free anterolateral thigh flap is an ideal choice for reconstruction of oral and maxillofacial defects, as it has many advantages such as reliable blood supply, large size available, and little donor site morbidity.

[The use of BD-018 medical natural absorbable surgical suture in oral and maxillofacial surgery].

The oral and maxillofacial cutaneous or/and oral mucous wound of 20 cases were sutured with BD-018 medical natural absorbable surgical suture. Fifteen cases with class I wound and five cases with class II wound healed well after operation. BD-018 medical natural absorbable surgical suture adapts to oral and maxillofacial cutaneous or/and oral mucous wound suturing.