Effect of tissue fixatives on the corrosion of biomedical magnesium alloys.

In this work, the corrosion behavior of pure Mg, Mg3Ag, Mg6Ag, and MgZnYNd alloys in different fixatives (ethyl alcohol (EA), 85 % ethyl alcohol (85 % EA), 10 % neutral buffered formalin (10 % NBF), 4 % glutaric dialdehyde (4 % GD), and 4 % paraformaldehyde (4 % PFA)) was investigated to provide a valuable reference for the selection of fixatives during the histological evaluation of Mg implants. Through the hydrogen evolution test, pH test, and corrosion morphology and product characterization, it was found that corrosion proceeded slowest in the EA and 85 % EA groups, slightly faster in 4 % GD, faster in 10 % NBF, and fastest in 4 % PFA. After corrosion, the EA group surface remained unchanged, while the 85%EA group surface developed minor cracks and warping. The 4%GD fixative formed a dense needle-like protective layer on the Mg substrate. The 10%NBF group initially grew a uniform layer, but later developed irregular pits due to accelerated corrosion. In contrast, the 4%PFA solution caused more severe corrosion attributed to chloride ions. The main corrosion products in the EA and 85%EA groups were MgO and Mg(OH)2, while the other fixatives containing diverse ions also yielded phosphates like Mg3(PO4)2 and MgHPO4. In 4 % PFA, AgCl formed on the surface of Mg6Ag alloy after corrosion. Therefore, to minimize Mg alloy corrosion without compromising staining quality, EA or 85 % EA is recommended, while 4 % PFA is not recommended due to its significant impact.

Bifidobacterium breve-derived indole-3-lactic acid ameliorates colitis-associated tumorigenesis by directing the differentiation of immature colonic macrophages.

Aim: To elucidate dynamics and functions in colonic macrophage subsets, and their regulation by Bifidobacterium breve (B. breve) and its associated metabolites in the initiation of colitis-associated colorectal cancer (CAC). Methods: Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to create a CAC model. The tumor-suppressive effect of B. breve and variations of macrophage subsets were evaluated. Intestinal macrophages were ablated to determine their role in the protective effects of B. breve. Efficacious molecules produced by B. breve were identified by non-targeted and targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The molecular mechanism was further verified in murine bone marrow-derived macrophages (BMDMs), macrophages derived from human peripheral blood mononuclear cells (hPBMCs), and demonstrated in CAC mice. Results: B. breve alleviated colitis symptoms, delayed colonic tumorigenesis, and promoted phenotypic differentiation of immature inflammatory macrophages into mature homeostatic macrophages. On the contrary, the ablation of intestinal macrophages largely annulled the protective effects of B. breve. Microbial analysis of colonic contents revealed the enrichment of probiotics and the depletion of potential pathogens following B. breve supplementation. Moreover, indole-3-lactic acid (ILA) was positively correlated with B. breve in CAC mice and highly enriched in the culture supernatant of B. breve. Also, the addition of ILA directly promoted AKT phosphorylation and restricted the pro-inflammatory response of murine BMDMs and macrophages derived from hPBMCs in vitro. The effects of ILA in murine BMDMs and macrophages derived from hPBMCs were abolished by the aryl hydrocarbon receptor (AhR) antagonist CH-223191 or the AKT inhibitor MK-2206. Furthermore, ILA could protect against tumorigenesis by regulating macrophage differentiation in CAC mice; the AhR antagonist largely abrogated the effects of B. breve and ILA in relieving colitis and tumorigenesis. Conclusion: B. breve-mediated tryptophan metabolism ameliorates the precancerous inflammatory intestinal milieu to inhibit tumorigenesis by directing the differentiation of immature colonic macrophages.

[Left mandibular osteonecrosis following herpes zoster of the third branch of left trigeminal nerve: A case report].

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection. Simple involvement of the third branch of trigeminal nerve was rare, and so were oral complications such as pulpitis, periodontitis, spontaneous tooth loss, bone necrosis, etc. This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis. We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago, and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication. A few days later, he developed gum pain in the left mandibular posterior tooth area. He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure. Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening. Visible herpes zoster pigmentation and scarring on the left side of the face appeared. The left mandibular posterior tooth was missing, the exposed bone surface was about 1.5 cm×0.8 cm, and the surrounding gingiva was red and swollen, painful under pressure, with no discharge of pus. The remaining teeth in the mouth were all Ⅲ degree loosened. Imageological examination showed irregular low-density destruction of the left mandible bone, unclear boundary, and severe resorption of alveolar bone. The patient was diagnosed as left mandibular osteonecrosis. Under general anesthesia, left mandibular lesion exploration and curettage + left mandibular partial resection + adjacent flap transfer repair were performed. The patient was re-exmained 6 months after surgery, there was no redness, swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced. Unfortunately, the patient had complications of postherpetic neuralgia. This case indicate that clinicians should improve their awareness of jaw necrosis, a serious oral complication of trigeminal zoster, and provide early treatment. After the inflammation was initially controlled, surgical treatment could be considered to remove the necrotic bone, curettage the inflammatory granulation tissue, and extraction of the focal teeth to avoid further deterioration of the disease.

Prediction of jaw opening function after mandibular reconstruction using subject-specific musculoskeletal modelling.

BACKGROUND: Mandibular reconstruction patients often suffer abnormalities in the mandibular kinematics. In silico simulations, such as musculoskeletal modelling, can be used to predict post-operative mandibular kinematics. It is important to validate the mandibular musculoskeletal model and analyse the factors influencing its accuracy. OBJECTIVES: To investigate the jaw opening-closing movements after mandibular reconstruction, as predicted by the subject-specific musculoskeletal model, and the factors influencing its accuracy. METHODS: Ten mandibular reconstruction patients were enrolled in this study. Cone-beam computed tomography images, mandibular movements, and surface electromyogram signals were recorded preoperatively. A subject-specific mandibular musculoskeletal model was established to predict surgical outcomes using patient-averaged muscle parameter changes as model inputs. Jaw bone geometry was replaced by surgical planning results, and the muscle insertion sites were registered based on the non-rigid iterative closest point method. The predicted jaw kinematic data were validated based on 6-month post-operative measurements. Correlations between the prediction accuracy and patient characteristics (age, pathology and surgical scope) were further analysed. RESULTS: The root mean square error (RMSE) for lower incisor displacement was 31.4%, and the error for peak magnitude of jaw opening was 4.9 mm. Age, post-operative infection and radiotherapy influenced the prediction accuracy. The amount of masseter detachment showed little correlation with jaw opening. CONCLUSION: The mandibular musculoskeletal model successfully predicted short-range jaw opening functions after mandibular reconstruction. It provides a novel surgical planning method to predict the risk of developing trismus.

FD-Net: Feature Distillation Network for Oral Squamous Cell Carcinoma Lymph Node Segmentation in Hyperspectral Imagery.

Oral squamous cell carcinoma (OSCC) has the characteristics of early regional lymph node metastasis. OSCC patients often have poor prognoses and low survival rates due to cervical lymph metastases. Therefore, it is necessary to rely on a reasonable screening method to quickly judge the cervical lymph metastastic condition of OSCC patients and develop appropriate treatment plans. In this study, the widely used pathological sections with hematoxylin-eosin (H&E) staining are taken as the target, and combined with the advantages of hyperspectral imaging technology, a novel diagnostic method for identifying OSCC lymph node metastases is proposed. The method consists of a learning stage and a decision-making stage, focusing on cancer and non-cancer nuclei, gradually completing the lesions' segmentation from coarse to fine, and achieving high accuracy. In the learning stage, the proposed feature distillation-Net (FD-Net) network is developed to segment the cancerous and non-cancerous nuclei. In the decision-making stage, the segmentation results are post-processed, and the lesions are effectively distinguished based on the prior. Experimental results demonstrate that the proposed FD-Net is very competitive in the OSCC hyperspectral medical image segmentation task. The proposed FD-Net method performs best on the seven segmentation evaluation indicators: MIoU, OA, AA, SE, CSI, GDR, and DICE. Among these seven evaluation indicators, the proposed FD-Net method is 1.75%, 1.27%, 0.35%, 1.9%, 0.88%, 4.45%, and 1.98% higher than the DeepLab V3 method, which ranks second in performance, respectively. In addition, the proposed diagnosis method of OSCC lymph node metastasis can effectively assist pathologists in disease screening and reduce the workload of pathologists.

[Application of double-layer soft tissue suture closure technique in the surgical treatment of patients with mandible medication-related osteonecrosis of the jaw of early and medium stages].

OBJECTIVE: To investigate the clinical application effect of double-layer soft tissue (DLST) suture closure technique in patients with mandible medication-related osteonecrosis of the jaw (MRONJ) of early and medium stages resulted in application of anti-bone-resorptive drugs. METHODS: Early to medium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking University School and Hospital of Stomatology from October 2021 to September 2022 were included. Clinical information of the patients were collected, including primary disease, concomitant disease, medication regimen (drug type, duration of medication), MRONJ stage, clinical symptoms, imaging manifestations, etc. During surgery, after using marginal mandibulae resection to remove the necrotic bone, the wound was closed using DLST closure technique. Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique, the pain score and functional status of the patiens were evaluated. RESULTS: This study totally included 13 patients, 12 women and 1 man, aged (66.69±13.14) years. Seven patients had osteoporosis, 2 had lung cancer, 3 had breast cancer and 1 had prostate cancer among their primary diseases; 7 had no concomitant diseases, 2 had diabetes mellitus, 2 had cardiovascular disease and 1 had dry syndrome. Intravenous zoledronic acid were used in 9 patients, the average duration was (37.7±20.0) months, and other drugs, such as letrozole tablets were taken in 7 patients at the same time; Denosumab injection was used in 3 patients for an average of (10.3±11.9) months; Alendronate sodium tablets were taken in 5 patients for an average of (55.20±27.20) months, and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 patients. The average post-operative follow-up was 11.9 months (9 to 17 months), and all the 13 patients were cured without complications, such as pus overflow and so forth. The pre-operative score of Karnofsky performance status (KPS) in the patients was 68.46±14.05, and the post-operative score was 82.31±15.36, and the difference was statistically significant (P < 0.05). The pre-operative score of visual analogue scale (VAS) in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51, and the difference had statistical significance (P < 0.001). CONCLUSION: The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the mandible using anti-bone-resorptive drugs alone, and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

Alveolar ridge preservation of two-wall bone defects using mineralized dentin matrix: An experimental pre-clinical study.

OBJECTIVES: To study bone healing of two-wall bone defects after alveolar ridge preservation using mineralized dentin matrix. MATERIALS AND METHODS: After distal roots extraction of second and fourth premolars (P2, P4) on one lateral mandible in 12 beagles, two-wall bone defects (5 × 5 × 5 mm) were surgically created distally to the remaining mesial roots of P2 and P4. A total of 24 sites were randomly allocated to three groups (implant material- time of execution): mineralized dentin matrix (MDM)-3 m (MDM + collagen membrane; 3 months), MDM-6 m (MDM particles + collagen membrane; 6 months), and C-6 m (collagen membrane only; 6 months). Clinical, radiographic, digital, and histological examinations were performed 3 and 6 months after surgery. RESULTS: The bone healing in MDM groups were better compared to Control group (volume of bone regenerated in total: 25.12 mm3 vs. 13.30 mm3, p = .046; trabecular volume/total volume: 58.84% vs. 39.18%, p = .001; new bone formation rate: 44.13% vs. 31.88%, p = .047). Vertically, the radiological bone level of bone defect in MDM-6 m group was higher than that in C-6 m group (vertical height of bone defect: 1.55 mm vs. 2.74 mm, p = .018). Horizontally, no significant differences in buccolingual bone width were found between MDM and C groups at any time or at any level below the alveolar ridge. The percentages of remaining MDM were <1% in both MDM-3 m and MDM-6 m groups. CONCLUSIONS: MDM improved bone healing of two-wall bone defects and might be considered as a socket fill material used following tooth extraction.

Evaluation of joint kinematics in patients with condylar reconstruction using mandibular motion simulation based on intraoral scanning registration.

AIM: To summarize the features of condylar kinematics in patients with condylar reconstruction using a mandibular motion simulation method based on intraoral scanning registration. MATERIALS AND METHODS: Patients undergoing unilateral segmental mandibulectomy and autogenous bone reconstruction as well as healthy volunteers were enrolled in the study. Patients were grouped based on whether the condyles were reconstructed. Mandibular movements were recorded using a jaw tracking system, and kinematic models were simulated after registration. The path inclination of the condyle point, margin of border movement, deviation, and chewing cycle were analyzed. A t test and one-way analysis of variance (ANOVA) were carried out. RESULTS: A total of 20 patients, including 6 with condylar reconstruction and 14 with condylar preservation as well as 10 healthy volunteers were included. The patients with condylar reconstruction showed flatter movement paths of the condyle points. The mean inclination angle of the condylar movement paths of the patients with condylar reconstruction (0.57 ± 12.54 degrees) was significantly smaller than that of those with condylar preservation (24.70 ± 3.90 degrees, P = 0.014) during both maximum opening and protrusion (7.04 ± 12.21 degrees and 31.12 ± 6.79 degrees, respectively, P = 0.022). The inclination angle of the condylar movement paths of the healthy volunteers was 16.81 ± 3.97 degrees during maximum opening and 21.54 ± 2.80 degrees during protrusion; no significant difference compared with the patients. The condyles of the affected side tended to deviate laterally in all patients during mouth opening and protrusion. Patients with condylar reconstruction showed more severe symptoms of mouth opening limitation and mandibular movement deviation as well as shorter chewing cycles than patients with condylar preservation. CONCLUSION: Patients with condylar reconstruction showed flatter movement paths of the condyle points, greater lateral motion range, and shorter chewing cycles than those with condylar preservation. The method of mandibular motion simulation based on intraoral scanning registration was feasible to simulate condylar movement.

Retrospective study of synovial chondromatosis of the temporomandibular joint: clinical and histopathologic analysis and the early-stage imaging features.

OBJECTIVE: Herein, we aimed to study the clinical, radiographical, and histopathologic features of synovial chondromatosis in the temporomandibular joint (SC in TMJ) and provide references for early diagnosis and treatment prognosis. STUDY DESIGN: The medical records and imaging examinations of patients with SC in TMJ, diagnosed using postoperative histopathologic examination, were reviewed and analyzed. Among them, 18 cases who lacked calcified loose bodies on spiral computed tomography or cone beam computed tomography (SCT/CBCT) were selected for further study. Descriptive statistical methods were used to analyze the clinical characteristics of patients. RESULTS: The study included 100 patients with SC in TMJ, who were predominantly female (male to female: 1:3), and were aged from 21 to 77 years (median, 47). Radiopaque calcified lesions on SCT/CBCT were missing in 18 cases, but cartilaginous nodules were observed during surgery. The cases lacking calcification had a relatively shorter disease course, suggesting they were in the early stages of SC. CONCLUSION: In the early stage of SC, although calcified loose bodies cannot be detected on SCT/CBCT, attention should be paid to the widening of the posterior superior joint space and sclerosis or slight erosion of the joint fossa. Magnetic resonance imaging would be helpful to detect the early-stage SC in TMJ.

Oral administration of Bifidobacterium breve improves anti-angiogenic drugs-derived oral mucosal wound healing impairment via upregulation of interleukin-10.

Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.

Designing customized temporomandibular fossa prosthesis based on envelope surface of condyle movement: validation via in silico musculoskeletal simulation.

Objective: This study presents an innovative articular fossa prosthesis generated by the envelope surface of condyle movement, and compares its mandible movements, muscle activities, and joint reaction forces with two temporomandibular joint (TMJ) prostheses using multibody musculoskeletal simulation. Methods: A healthy 23-year-old female was recruited for this study. Cone-beam computed tomographic (CBCT) was performed to reconstruct the mandibular bone geometry. A customized TMJ fossa prosthesis was designed based on the subject-specific envelope surface of condyle movement (ESCM). Mandibular kinematics and jaw-closing muscle electromyography (EMG) were simultaneously recorded during maximum jaw opening-closing movements. To validate our prosthesis design, a mandibular musculoskeletal model was established using flexible multibody dynamics and the obtained kinematics and EMG data. The Biomet fossa prosthesis and the ellipsoidal fossa prosthesis designed by imitating the lower limb prostheses were used for comparison. Simulations were performed to analyze the effects of different fossa prostheses on jaw opening-closing motions, mandibular muscle activation, and contact forces. Results: The maximum opening displacement for the envelope-based fossa prosthesis was greater than those for Biomet and ellipsoidal prostheses (36 mm, 35 mm, and 33 mm, respectively). The mandibular musculoskeletal model with ellipsoidal prosthesis led to dislocation near maximal jaw opening. Compared to Biomet, the envelope-based fossa reduced the digastric and lateral pterygoid activation at maximal jaw opening. It also reduced the maximal resistance to condylar sliding on the intact side by 63.2 N. Conclusion: A customized TMJ fossa prosthesis was successfully developed using the ESCM concept. Our study of musculoskeletal multibody modeling has highlighted its advantages and potential. The artificial fossa design successfully achieved a wider condylar range of motion. It also reduced the activation of jaw opening muscles on the affected side and resistance on the intact side. This study showed that an ESCM-based approach may be useful for optimizing TMJ fossa prostheses design.

Bacterial distribution and inflammatory cytokines associated with oral cancer with and without jawbone invasion-a pilot study.

OBJECTIVE: To explore the bacterial and inflammatory variations in oral cancer patients with and without jawbone invasion. MATERIALS AND METHODS: A total of 20 specimens of fresh tumor tissue, including 10 from the tumor-invaded jawbone (JIOC group) and 10 without jawbone invasion (NJIOC group), were collected from oral cancer patients. Meanwhile, 10 specimens from normal oral mucosa were collected from healthy patients (control group). The microbiomic content of each sample was analyzed by 16S rRNA gene sequencing, while the expression of inflammatory cytokines was assessed using protein microarray analysis. RESULTS: There was a significant difference in ß diversity between JIOC and NJIOC groups (P < 0.05), but no difference between NJIOC and control groups. The average relative abundance of Fusobacteria and Spirochaetes was higher, while Firmicutes was lower in the JIOC group than in the NJIOC group (all P < 0.05). The expression of pro-inflammatory cytokines like interleukin (IL)-1α, IL-1ß, IL-4, and IL-8 was upregulated in the JIOC group compared with the NJIOC group, while MCP-1 was decreased (all P < 0.05). Slackia spp. and Howardella spp. were positively correlated with IL-4; Odoribacter spp. and Acidaminococcaceae spp. were negatively correlated with IL-4, and Clostridium XIVa spp. was negatively correlated with IL-1α and IL-1ß. CONCLUSION: Bacterial and inflammatory differences were observed in oral cancer patients with and without jawbone invasion, where the relative abundance of the differential bacteria was associated with the expression of the inflammatory cytokines. CLINICAL RELEVANCE: This study investigated the changes in the flora during jawbone invasion in oral cancer and its effect on inflammatory factors, elucidating the possible mechanisms of jawbone invasion caused by oral cancer, which may lead to new ideas for the clinical prevention and treatment of jawbone invasion in oral cancer.

Long-Term Temporospatial Complementary Relationship between Degradation and Bone Regeneration of Mg-Al Alloy.

The utilization of guided tissue regeneration membranes is a significant approach for enhancing bone tissue growth in areas with bone defects. Biodegradable magnesium alloys are increasingly being used as guided tissue regeneration membranes due to their outstanding osteogenic properties. However, the degradation rates of magnesium alloy bone implants documented in the literature tend to be rapid. Moreover, many studies focus only on the initial 3-month period post-implantation, limiting their applicability and impeding clinical adoption. Furthermore, scant attention has been given to the interplay between the degradation of magnesium alloy implants and the adjacent tissues. To address these gaps, this study employs a well-studied magnesium-aluminum (Mg-Al) alloy membrane with a slow degradation rate. This membrane is implanted into rat skull bone defects and monitored over an extended period of up to 48 weeks. Observations are conducted at various intervals (2, 4, 8, 12, 24, and 48 weeks) following the implantation. Assessment of degradation behavior and tissue regeneration response is carried out using histological sections, micro-CT scans, and scanning electron microscopy (SEM). The findings reveal that the magnesium alloy membranes demonstrate remarkable biocompatibility and osteogenic capability over the entire observation duration. Specifically, the Mg-Al alloy membranes sustain their structural integrity for 8 weeks. Notably, their osteogenic ability is further enhanced as a corrosion product layer forms during the later stages of implantation. Additionally, our in vitro experiments employing extracts from the magnesium alloy display a significant osteogenic effect, accompanied by a notable increase in the expression of osteogenic-related genes. Collectively, these results strongly indicate the substantial potential of Mg-Al alloy membranes in the context of guided tissue regeneration.

Erratum: [Corrigendum] Inhibition of human oral squamous cell carcinoma proliferation and migration by prodrug­activating suicide gene therapies.

[This corrects the article DOI: 10.3892/etm.2023.11790.].

Prediction of condylar movement envelope surface based on facial morphology.

The present study aimed to predict the envelope surfaces from facial morphology. Condylar envelope surfaces for 34 healthy adults were formed and simplified as sagittal section curves. Cephalometric and maximum mandibular moving distances measurement were performed on the participants. There was no statistically significant difference (p = 0.763) between the left and right maximum lateral movements. There was a statistically significant difference in the mandibular body length between the sexes. The envelope surfaces were divided into type 1 with Hp2 ≥ 1/3 Hp1 and type 2 with Hp2 < 1/3 × Hp1. SNA and SNB for type 2 were significantly greater than those for type 1 (p < 0.001). Therefore, the participants were divided into four groups based on gender and envelope surface morphology. The curves could be fitted using the second-order Fourier function (R-square ≥0.95). Six facial parameters were selected and a matrix was used to map facial morphology to the envelope surface. Individual sagittal curves were predicted using the matrix and facial parameters, and the envelope surface was predicted using the curve and the condyle model. Deviation analysis for the predicted envelope surface using the actual envelope as a reference was carried out (root mean square = 0.9970 mm ± 0.2918 mm). This method may lay a foundation for the geometric design of artificial fossa components of temporomandibular joint replacement systems. It may improve prosthesis design without flexible tissue repair and guide the movement of the artificial joint head.

Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts.

BACKGROUND: Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients. METHODS: The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket. RESULTS: Patients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib. CONCLUSION: Our findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs.

MicroRNA in medication related osteonecrosis of the jaw: a review.

Medication related osteonecrosis of the jaw (MRONJ) is a condition caused by inhibition of the osteoclast activity by the anti-resorptive and anti-angiogenic drugs. Clinically, there is an exposure of the necrotic bone or a fistula which fails to heal for more than 8 weeks. The adjacent soft tissue is inflamed and pus may be present as a result of the secondary infection. To date, there is no consistent biomarker that could aid in the diagnosis of the disease. The aim of this review was to explore the literature on the microRNAs (miRNAs) related to medication related osteonecrosis of the jaw, and to describe the role of each miRNA as a biomarker for diagnostic purpose and others. Its role in therapeutics was also searched. It was shown that miR-21, miR-23a, and miR-145 were significantly different in a study involving multiple myeloma patients as well as in a human-animal study while miR-23a-3p and miR-23b-3p were 12- to 14-fold upregulated compared to the control group in an animal study. The role of the microRNAs in these studies were for diagnostics, predictor of progress of MRONJ and pathogenesis. Apart from its potential diagnostics role, microRNAs have been shown to be bone resorption regulator through miR-21, miR-23a and miR-145 and this could be utilized therapeutically.

Endoscopic visualization of the inferior alveolar nerve associated with somatosensory changes after impacted mandibular third molar extraction.

The aim of this study is to assess the relationship between somatosensory functional changes and inferior alveolar nerve (IAN) exposure after impacted mandibular third molars (M3M) removal. We recruited 35 patients who underwent impacted M3M extraction near the IAN. The M3Ms were extracted by combined endoscopy, piezosurgery, and contra-angle high-speed turbine handpiece. All IAN canal perforations and exposed regions were recorded and measured by endoscopy after extraction and on cone-beam computed tomography (CBCT) images before extraction. The patients were followed up 1, 7, and 35 days after surgery. A standardized quantitative sensory testing (QST) battery was performed on the lower lip skin. All of 35 cases had exposed IAN on CBCT images, 5 of which had no exposed IAN under endoscopy. For the other 30 cases, the endoscopy-measured IAN length and width were shorter than the CBCT measurements (P < 0.001). The warm and mechanical detection thresholds (MDT) on the operation side were significantly higher than the contralateral side after surgery (P < 0.05). Thermal sensory limen, MDT, and cold pain threshold were strongly correlated with the exposed IAN length and MDT also with the exposed IAN width one day after surgery. In conclusion, it was found that not all exposed IAN in CBCT images were real exposure after surgery. The intraoperative exposed IAN endoscopic measurements were smaller than by CBCT and strongly correlated with some QST parameters.