Chinese Journal of Stomatology

The repair of osteochondral damage is clinically challenging. There are some limitations in the current technologies for osteochondral repair and regeneration, and it is still difficult for the strategies for osteochondral tissue engineering to obtain lasting and effective outcomes. The emergence and development of three-dimensional (3D) bioprinting have provided novel and powerful technical means for the reconstruction of osteochondral tissue. The controlled deposition of bioactive materials makes it possible to accurately reconstruct the heterogeneous microstructure of osteochondral tissue. This article summarizes the latest developments in the field of osteochondral bioprinting, including scaffold-based bioprinting, scaffold-free bioprinting, and in situ bioprinting. At the same time, the major considerations of osteochondral bioprinting are discussed, and current solutions and research trends are proposed, to broaden the understanding of readers about 3D bioprinting of osteochondral tissue.

Y Wu

Zhonghua kouqiang yixue zazhi

[Application of the three-dimensional bioprinting for the osteochondral tissue regeneration].

三维生物打印在骨软骨组织再生中的应用

Objective: To summarize the etiological characteristics and clinical treatment effects of 17 patients with medication-related osteonecrosis of the jaw (MRONJ). Methods: The clinical data of 17 patients with MRONJ admitted to the Department of Oral and Maxillofacial Surgery, the First People's Hospital of Jinzhong, Shanxi Province, from July 2016 to December 2019 were retrospectively analyzed, including 9 males and 8 females, aged (63.6±9.6) years old (43-82 years old). Descriptive analysis of the primary disease, onset factors, site of disease, clinical manifestations, treatment methods, and treatment effects was conducted through follow-up for at least 1 year. Results: Among the primary diseases of the 17 cases, 12 were malignant tumors, and 5 were osteoporosis. There were 13 cases with a history of a trigger event (tooth extraction or unsuited removable denture). Six cases occurred in the maxilla, 10 cases occurred in the mandible, and 1 case involved both the upper and lower jaws. For the most common medication used, bisphosphonate was used in 16 cases including 5 cases with concomitant use of angiogenesis-inhibiting drugs. There was 1 case resulted from receptor activator of NF-κB ligand (RANKL) monoclonal antibody application. The duration of medication application was (10.1±3.9) months (3-18 months). All 17 cases were treated surgically. Totally 15 patients healed well after surgical treatment and the other 2 patients, who had poor soft tissue healing after surgery, healed well after a second operation. Conclusions: Tooth extraction might be a major trigger factor for the onset of MRONJ in the mandible. The disease was more possibly occured in the mandible than in the maxilla. Appropriate surgical treatment could achieve a good clinical outcome.

W Hou

X T Dong

T T Wu

X F Ma

X H Zhang

C L Hou

X H Liu

[Preliminary study on the etiological characteristics and clinical treatment of medication-related osteonecrosis of the jaws].

[药物相关性颌骨坏死的病因特征及临床治疗的初步研究]

Objective: To study the relationship between zoledronic acid (ZOL) and vascular endothelial growth factor (VEGF) conformation so as to reveal the mechanism of bisphosphonates inhibiting angiogenesis. Methods: The binding structures of ZOL and VEGF were preprocessed and the molecular dockings were simulated through AutoDockTools, Discovery studio4 and AutoDockVina. The best binding conformation was accurately screened. The effects of various concentrations of ZOL (group A was 0 μmol/L, groups B, C and D were 25, 50 and 100 μmol/L, respectively) on human umbilical vein endothelial cell (HUVEC) proliferation, angiogenesis and angiogenic molecules were detected by using cell counting kit-8 (CCK-8) in vivo and in vitro angiogenesis, immunofluorescence and Western blotting. Results: There was a ZOL binding site on the target protein VEGF conformation. The affinity was -5.2 kcal/mol. This binding site consisted of the hydrophobic region composed of amino acids Cys26, 51, 57, etc. and the hydrogen bond binding region of the A chain (ASP34, SER50) and B chain (CYS61, 68, LEU66, GLY59). The results of CCK-8 showed that the levels of value A in groups B, C and D were significantly lower than that in group A at each time point from 3 to 6 days (P<0.05). In vitro vascular experiments demonstrated that the numbers of budding in groups B, C and D [(208±28), (151±21) and (62±9), respectively] were significantly lower than that in group A (276±30) (P<0.05). In vivo vascular experiments displayed that the ratio of Matrigel gel/plasma fluorescence in group A (0.003 1±0.000 3) was significantly higher than those in group B (0.002 1±0.000 2), group C (0.001 6±0.000 2) and group D (0.000 6±0.000 1) (P<0.05). The results of Western blotting revealed that the expression of VEGF in groups B, C and D [(0.72±0.11), (0.41±0.07) and (0.24±0.04), respectively] were significantly lower than that in group A (1.01±0.02) (P<0.05), and the expression levels of hypoxia-inducible factor-1α (HIF-1α) in groups B, C and D [(0.68±0.09), (0.55±0.06) and (0.43±0.08), respectively] were significantly lower than that in group A (0.96±0.04) (P<0.05). Conclusions: ZOL could inhibit cell proliferation, in vivo and in vitro vascularization and expression of VEGF/HIF-1α. The binding site of ZOL with the conformation of VEGF was located in the hydrophobic region and hydrogen-bonding region of amino acids. Designing an antagonist targeting this site might potentially alleviate the effect of ZOL in inhibiting angiogenesis.

R J Wang

Q T Zhao

Y J Yu

Y Q Zhou

S Y Wang

Molecular mechanism of zoledronic acid inhibiting angiogenesis by semi flexible binding with vascular endothelial growth factor conformation

唑来膦酸通过半柔性结合血管内皮生长因子构象抑制血管生成的分子机制

Objective: To investigate the effect of low dose lipopolysaccharide (LPS)-treated human periodontal ligament stem cells (HPDLSC) on the expression of macrophage pro-inflammatory factors and the mechanism involved. Methods: The primary HPDLSCs were obtained from healthy third molar periodontal ligament tissue. Phosphate buffer saline (PBS), 100 μg/L or 10 mg/L of LPS were used to treat HPDLSCs for 48 h, and their conditioned media were respectively co-cultured with THP-1-derived macrophages for 48 h. The corresponding experimental groups were PBS-treated HPDLSC-derived conditioned medium (CM-C) group, low dose LPS-treated HPDLSC-derived conditioned medium (CM-L) group, and high dose LPS-treated HPDLSC-derived conditioned medium (CM-H) group. Quantitative real-time PCR was performed to explore the mRNA expressions of macrophage interleukin (IL)-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α) in the CM-C, CM-L and CM-H groups, and the expressions of nuclear factor (erythroid-derived 2)-like 2 (NRF2), glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H quinone dehydrogenase 1 (NQO1) and heme oxygenase 1 (HO-1) in the CM-C and CM-L groups. Meanwhile, Western blotting was used to detect the change of nuclear and cytoplasmic NRF2 and the levels of GCLC and HO-1 in the CM-C and CM-L groups. The 2', 7'-dichlorofluorescein probe was adopted to detect the reactive oxygen species (ROS) levels of macrophages in the CM-C and CM-L groups and the data were characterized by the mean fluorescent intensity (MFI). Results: The mRNA expressions of macrophage pro-inflammatory factors IL-6, IL-8, IL-12 and TNF-α in the CM-H group (2.332±0.594, 3.601±0.639, 2.120±0.677 and 2.468±0.236) were significantly upregulated compared with those in the CM-C group (1.000±0.321, 1.000±0.151, 1.000±0.059 and 1.000±0.095) (P<0.05); while the relative mRNA levels of IL-6, IL-12 and TNF-α in the CM-L group (0.056±0.002, 0.215±0.024 and 0.567±0.071) were much lower than those in the CM-C group (1.000±0.209, 1.000±0.220 and 1.000±0.220) (P<0.05). At the mRNA level, the expression of NRF2 was significantly increased in the CM-L group (1.864±0.198) compared with that in the CM-C group (1.000±0.094) (P<0.05). At the protein level, the cytoplasmic NRF2 and nuclear NRF2 were increased in CM-L group (1.175±0.104 and 1.308±0.082) compared with those in the CM-C group (1.000±0.025 and 1.000±0.049) (P<0.05). Furthermore, the antioxidative genes, i.e. GCLC and NQO1, localized in NRF2 downstream, were significantly upregulated in the CM-L group (1.786±0.278 and 1.444±0.078) compared with the CM-C group (1.000±0.139 and 1.000±0.226) (P<0.05). The protein levels of GCLC and HO-1 were augmented in the CM-L group (1.159±0.036 and 1.412±0.075) in contrast with those in the CM-C group (1.000±0.050 and 1.000±0.013) (P<0.05). In addition, the MFI in the CM-L group (123 419±1 302) was significantly lower than that in the CM-C group (139 193±1 241) (P<0.05). Conclusions: Low-dose LPS-treated HPDLSCs could regulate oxidative stress response through activating the NRF2 signaling pathway of macrophages and further downregulating the expressions of macrophage pro-inflammatory factors.

Y Z Wang

D D Fei

Y Zhang

X G Zhang

Y Wang

Q T Wang

[Role and mechanism of low-dose lipopolysaccharide-treated human periodontal ligament stem cells on the expression of macrophage pro-inflammatory factors].

[低剂量脂多糖处理的人牙周韧带干细胞对巨噬细胞促炎因子表达的作用及机制]

牙列重度磨耗可严重影响患者的口腔美观和咬合功能，治疗时不仅需要美学重建，还需要咬合重建。咬合重建包括咬合设计、咬合表达和咬合实现。咬合表达即使用牙合垫、诊断饰面、临时冠等诊断性临时修复体，将咬合设计建立的上下颌基准诊断性咬合关系从无创、微创到有创，逐级诊断、验证、调改、磨合，最后获得最适合患者的最终修复体咬合关系。咬合表达的关键是从牙合垫到诊断饰面和（或）临时冠到最终修复体咬合关系的逐级复制和转移，将调改磨合后的咬合关系精确逐级复制和转移至下一个治疗环节。本文重点介绍牙列重度磨耗全口咬合重建中如何一步一步做好咬合关系的复制和转移。.

J G Tan

[Interocclusal relationship transfer for full-mouth rehabilitation: step by step].

全口义齿修复中的咬合关系转移：一步一步指南

In this paper, the clinical application and basic research progress of periodontally accelerated osteogenic orthodontics technology (PAOO) are introduced in detail. The key contents include: the development and evolution of minimally invasive, simplified and digital clinical methods of corticotomy; the role, significance and improvement of bone augmentation surgery; factors affecting tooth movement rate and treatment course; indications, contraindications and complications; prognosis and stability; basic research status of PAOO.

J H Jiang

[Application, research and prospect of periodontally accelerated osteogenic orthodontics technology].

[牙周加速成骨正畸技术的应用、研究与展望]。

Bimaxillary protrusion is a clinical condition with high prevalence rate, which damages facial esthetics and affects the mental health of patients. Its clinical manifestations include protrusion of lips, overexposure of teeth, vertical and sagittal overdevelopment of alveolar bone in the anterior areas of upper and lower anterior jaws, and so on. The common protocols for the treatment of severe bimaxillary protrusion is orthodontic treatment with exaction of premolars or combined orthognathic-orthodontic treatment. However, either method is of great difficulty. By systematic mechanical design, the author used the treatment system of customized lingual appliances associated with corticotomy to realize the vertical and torque control of the anterior teeth, and obtain the orthodontic treatment effect of both esthetics and health. The clinical strategies for the treatment of severe bimaxillary protrusion were provided.

B Fang

Application of corticotomy associated with customized lingual orthodontics in treatment of severe bimaxillary protrusion in adults

成人严重双颌前突治疗中皮质切开术联合个性化舌侧正畸的应用

Objective: To investigate the effects of combination treatment of photodynamic therapy (PDT) based on photosensitizer chlorin e6 (Ce6) and antibiotic agent tinidazole (TNZ) against periodontitis both in vitro and in vivo. Methods: The Sprague-Dewley (SD) rat periodontitis model was constructed using the method of orthodontic wire ligation. After successful modeling, SD rats were randomly divided into the following 6 groups (3 rats in each group): positive control (Ctrl+), Ce6, TNZ, a mixture of Ce6 and TNZ (Ce6/TNZ), Ce6 with laser irradiation (Ce6+L), a mixture of Ce6 and TNZ with laser irradiation (Ce6/TNZ+L). Methyl thiazolyl tetrazolium (MTT) assay was used to assess the cytotoxic activities of Ce6 (concentration range: 0-20 mg/L), TNZ (concentration range: 0-16.6 mg/L) and their mixture (Ce6/TNZ) in mouse fibroblast L929 cells. Fluorescence probe method was applied to measure the production of reactive oxygen species in the dental plaque biofilms after various treatments with and without 5-minute laser irradiation at 635 nm at a power density of 0.5 W/cm2 (Ce6+L and Ce6/TNZ+L groups), thus to evaluate the PDT performances. Cell counting kit-8 (CCK-8) and live/dead staining were used to assess the antibacterial activity in each of the groups and the combination index (CI) of PDT combined with TNZ was calculated subsequently. Flow cytometry was utilized to detect the apoptosis-inducing effects of these treatments in macrophage RAW264.7 cells after processing with the apoptosis detection kit. The inhibitory effects of various treatments on the absorption of alveolar bone of SD rats were further evaluated in the periodontitis rats by using the micro-CT. Results: The survival rates of L929 cells in the preset concentration range were all above 90% in Ce6, TNZ and Ce6/TNZ groups. Upon laser irradiation, the plaque biofilms in Ce6 and Ce6/TNZ groups showed significant green fluorescence, indicating that large amounts of reactive oxygen species were triggered and generated significantly in the dental plaque biofilms. However, the survival rates of dental plaque microorganisms in 5 Ce6/TNZ concentrations were (85.4±5.5)%, (76.0±8.9)%, (61.7±0.6)%, (56.3±2.6)% and (43.5±0.6)% respectively, which were significantly lower than that in Ce6 only and TNZ only groups (P<0.01). The CI levle of each drug concentration group was less than 1.0, which showed a significant synergistic antibacterial efficiency. Stronger apoptotic activities were observed in Ce6+L and Ce6/TNZ+L groups compared with those in Ce6 only and Ce6/TNZ only groups (P<0.01). In periodontitis rats, Ce6/TNZ combined laser irradiation could effectively inhibit the absorption of alveolar bone. The alveolar bone volume and the ratio of bone volume and tissue volume were (1.49±0.07) mm3 and (47.08±0.71)%, respectively. The distances between cementoenamel junction to alveolar bone crest on buccal and palatal sites decreased to (2.13±0.07) mm and (1.94±0.10) mm respectively, showing a high inhibition efficiency. Conclusions: Ce6-mediated PDT combined with TNZ possessed notable synergistic effects against periodontitis, reflecting in the efficient antibacterial effect, the apoptosis-inducing action on macrophages, and the inhibitory efficacy on the alveolar bone absorption in vivo.

W Pan

Z Y Li

T Zhang

E Y Shi

J Y Deng

Y S Wang

[In vitro and in vivo anti-periodontitis effects of combination treatment of photodynamic and antibiotic therapies].

[光动力疗法与抗生素联合治疗对牙周炎的体外和体内抗炎作用]

Objective: To evaluate the effect of quantitative analysis of optical signal in the near infrared fluorescence molecular navigation surgery for oral squamous cell carcinoma (OSCC). Methods: SCC9, HSC3 and epithelial cell lines (Leuk-1) were co-cultured with indocyanine green (ICG) for 6 hours in vitro in order to verify whether the quantitative analysis of near infrared optical signal could distinguish tumor cells from normal cells. A total of 16 BALB/c male mice (5-6 weeks, 20-25 g) were selected and fed in clean grade equipment and were equally divided into two groups. SCC9 and HSC3 cells were inoculated into the back of each mouse at a concentration of 1×106 cells/ml to establish a subcutaneous graft tumor model. The 5 mg/kg ICG was injected into the caudal vein to each of the tumor bearing mouse and the difference between OSCC and normal tissues was then analyzed by near infrared optical signal quantitative analysis (Paired t test). Ten patients with OSCC were enrolled in the Department of Stomatology of the First Affiliated Hospital of Bengbu Medical College from November 2019 to July 2020, including 6 patients with tongue squamous cell carcinoma and 4 patients with buccal squamous cell carcinoma.The patients were 6 males and 4 females and the range of age was from 46 to 71 years with an average age of 58.6 years. These patients were injected ICG (0.75 mg/kg) via the cubital vein at 6-8 h before surgery. Intraoperatively, the fluorescence intensities (FI) of near infrared signal were measured at tumor, peritumor tissues (2.0 cm beyond the tumor boundary) and normal tongue or buccal mucosa respectively. The signal background ratios (SBR) from the three site groups were assessed using one-way ANOVA followed by the Tukey post hoc test for multiple comparisons. Results: In vitro, the levels of near infrared FI in HSC3 and SCC9 groups were higher than that in Leuk-1group (P<0.01). In vivo, the result showed that the SBR of OSCC and normal tissues was 8.67±0.35. Clinical studies showed that the intensity of tumor [(408.23±101.51) arbitrary units (AU)] was significantly higher than those of peritumoral [(253.12±64.89) AU] and normal tissues [(261.50±80.47) AU] respectively. The SBRs of near infrared FI of tumor and peritumoral tissues, tumor and normal tissues were 1.61±0.53 and 1.56±0.48 respectively, while that of peritumoral and normal tissues was 0.96±0.17. Conclusions: The quantitative analysis of near infrared optical signal could distinguish OSCC from normal cells and could locate the OSCC tissue intraoperatively. Optical signal quantification and ICG near infrared fluorescence molecular technology possessed the feasibility in primary OSCC resection.

Y F Chen

K Zhang

S K Liao

N Li

L Liu

X Hong

C Liu

Y X Wang

Quantitative analysis of near infrared optical signal in fluorescence molecular navigation surgery for oral squamous cell carcinoma

口腔鳞状细胞癌荧光分子导航手术中近红外光学信号的定量分析

Objective: To assess the longitudinal changes in oral health-related quality of life (OHRQoL) and the denture satisfaction of immediate rehabilitation by implant-supported full-arch prostheses in patients of the edentulous and potential edentulous jaws. Methods: Patients in the Department of Implantology, Peking University School and Hospital of Stomatology from April 2008 to November 2020 were enrolled in the study. The treatment group (TG) consisted of 73 patients who had been treated with immediate rehabilitation by using implant-supported full-arch prostheses while the control group (CG) consisted of 31 patients who would be treated with immediate rehabilitation of implant-supported full-arch prostheses. The mean age of the patients in the treatment group was (57.5±11.1) years (ranged 31-79) and the average follow-up duration was 5.5±2.9 years (ranged 1-12). The OHRQL ratings were collected using oral health impact profile-20 (OHIP-20) and the visual analogue scales (VAS) was used to assess the denture satisfaction including stability, aesthetics, mastication, ease of cleaning, speaking and general satisfaction. Independent t-test, Mann-Whitney U-test and locally weighted scatterplot smoothing were applied for data analysis. Results: The cumulative survival rate (CSR) of the implants was 97.6% (450/461). The CSR of the prostheses was 93.3% (98/105). The average peri-implant marginal bone loss (MBL) was (0.8±0.4) mm and (1.2±0.6) mm after 1 and 5 years, respectively. The mean OHIP-20 total scores of TG and CG were 5(7) and 32.9±12.6, respectively, which had statistical difference between the two groups (P<0.001). The general satisfaction in the TG was 95.0(10.0), while the higher scores were for chewing [100.0(7.5)] stability [100.0(10.0)] and esthetics [100.0(10.0)] and the lower scores were for ease of cleaning [85.0(25.0)] and speaking ability [100.0(12.5)]. With prolonged follow-up, the total OHIP-20 score decreased significantly at first and then remained stable with minor fluctuations. Conclusions: Based on the present study, immediate rehabilitation with implant-supported full-arch prostheses was a feasible treatment program that had a long-term positive impact on OHRQoL, provided strong psychological and sociological support to the patients and restored the chewing and speech functions effectively.

T S Xu

P Di

X Jiang

J Luo

Y Lin

[Implant-supported fixed full-arch prostheses on oral health-related quality of life and denture satisfaction].

[种植支持式固定全口义齿对口腔健康相关生活质量和义齿满意度的影响]

ISSN	1002-0098
h-index	16

Publication Information	Publisher: Chinese Medical Journals Publishing House Co.Ltd，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2020，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 0.00%

Chinese Journal of Stomatology

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