Aims: This study aimed to elucidate the alterations in Follistatin-like protein 1 (FSTL1) and its association with the pathological process of periodontitis. Methods: This study included 48 patients with periodontitis and 42 healthy controls. The expression level of FSTL1 in the gingiva was determined by RT-qPCR, validated using the dataset GSE16134, and subsequently examined by western blotting. Bioinformatics analysis revealed a single-cell distribution of FSTL1, characteristic of angiogenesis and immune cell infiltration. The expression and distribution of FSTL1, vascular endothelial marker protein CD31 and myeloperoxidase (MPO), the indicator of neutrophil activity, were determined by immunohistochemistry (IHC). A series of correlation analyses was performed to determine the associations between FSTL1 and clinical parameters, including probing depth (PD) and clinical attachment loss (CAL), and their potential role in angiogenesis (CD31) and neutrophil infiltration (MPO). Results: FSTL1 was significantly upregulated in the gingiva of patients with periodontitis compared to their healthy counterparts. In addition, FSTL1 was positively correlated with the clinical parameters PD (r = .5971, p = .0005) and CAL (r = .6078, p = .0004). Bioinformatic analysis and IHC indicated that high FSTL1 expression was significantly correlated with angiogenesis and neutrophil infiltration in periodontitis. Moreover, receiver operating characteristic (ROC) analysis demonstrated that FSTL1 could serve as an independent indicator for evaluating the severity of periodontitis (area under the curve [AUC] = 0.9011, p < .0001). Conclusion: This study demonstrated FSTL1 upregulation in periodontitis and its potential contribution to the disease via angiogenesis and neutrophil infiltration.

Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/β-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.

BACKGROUND:The objective was to evaluate the level of neutrophil extracellular traps (NETs) in patients with chronic kidney disease (CKD) and periodontitis, and to explore the relationship between NETs and both diseases. METHODS:63 CKD and 40 non-CKD participants were recruited and underwent periodontal examination, among which 35 early CKD patients underwent periodontal therapy. The concentrations of NETs were determined by dsDNA assay in gingival crevicular fluid (GCF) and plasma, and by flow cytometry or immunofluorescence assay in blood and gingival tissues. The correlations between NETs and clinical parameters were analyzed. The influence of periodontal therapy on periodontitis, CKD and NETs concentrations was also evaluated. RESULTS:CKD patients had higher concentrations of NETs in plasma than non-CKD patients, and NETs concentrations were also increased in both GCF and plasma of patients with periodontitis than that of periodontally healthy patients. NETs concentrations were positively correlated with increased clinical parameters of CKD and periodontitis. The positive correlation between CKD and periodontitis was demonstrated. Moreover, periodontal therapy ameliorated periodontitis and CKD, and reduced NETs concentrations in GCF of patients. CONCLUSIONS:This study revealed that NETs might be a possible bridge between periodontitis and CKD, and suggested the potential target for therapy.

Background Mechanosensitive ion channel PIEZOs have been widely reported to involve inflammation and pain. This study aimed to clarify expression patterns of PIEZOs and their potential relations to irreversible pulpitis.Materials and methods Normal pulp tissues (n = 29) from patients with impacted third molars and inflamed pulp tissues (n = 23) from patients with irreversible pulpitis were collected. Pain levels were assessed using a numerical rating scale. PIEZO expressions were measured using real-time PCR and then confirmed using GEO datasets GSE77459, immunoblot, and immunohistochemistry staining. Correlations of PIEZO mRNA expression with inflammatory markers, pain markers, or clinical pain levels were evaluated using Spearman's correlation analysis. Univariate analysis was conducted to analyze PIEZO expressions based on pain description and clinical examinations of cold test, percussion, palpation, and bite test.Results Compared with normal pulp tissues, mRNA expression levels of PIEZO1 were significantly increased in inflamed pulp tissues, while PIEZO2 was significantly decreased, which was further confirmed in GSE77459 and on a protein and histological level. The positive correlation of the mRNA expression levels between PIEZO1 and inflammatory markers, as well as between PIEZO2 and pain markers, was verified. PIEZO2 expression was also positively correlated with pain levels. Besides, irreversible pulpitis patients who reported continuous pain and who detected a positive response to cold stimulus exhibited a higher expression level of PIEZO2 in the inflamed pulp tissues. By contrast, patients reporting pain duration of more than one week showed a higher expression level of PIEZO1.Conclusions This study demonstrated the upregulation of PIEZO1 and the downregulation of PIEZO2 in irreversible pulpitis and revealed the potential relation of PIEZO1 and PIEZO2 to inflammation and pain. These findings suggested that PIEZOs might play critical roles in the progression of irreversible pulpitis and paved the way for further investigations aimed at novel therapies of irreversible pulpitis by targeting PIEZOs.

AIM:To establish a reproducible experimental animal model for systemic lupus erythematosus (SLE)-associated periodontitis (PD), investigate the effects of SLE on PD and assess the therapeutic potential of alpha-ketoglutarate (αKG) for SLE-PD treatment. MATERIALS AND METHODS:An SLE-PD murine model was established via ligature-induced PD in MRL-lpr strain, with MRL/MpJ strain as a non-SLE control. The periodontal state was assessed using micro-CT, real-time PCR, histology, immunofluorescence and flow cytometry assays. αKG levels were analysed, and a thermoresponsive gel was designed as a periodontal dimethyl (DM)-αKG delivery system. αKG levels were analysed in gingival crevicular fluid (GCF) of PD patients with or without SLE. RESULTS:SLE significantly increased the periodontal inflammation and bone resorption in the SLE-PD model. αKG levels in GCF were lower in PD patients with SLE than in PD patients without SLE. Decreased αKG levels in the gingiva and macrophage M1/M2 imbalance were observed in SLE-PD mice. However, DM-αKG thermoresponsive gel effectively alleviated the periodontal inflammation, bone resorption and macrophage M1/M2 imbalance in SLE-PD mice. CONCLUSIONS:Our study established, for the first time, a novel SLE-PD murine model and revealed that SLE increases the severity of PD in vivo. Our findings highlight the therapeutic potential of αKG for SLE-associated PD.

Background The reduced treatment time of dental implants with immediate loading protocol is an appealing solution for dentists and patients. However, there remains a significant risk of early peri-implant bone response following the placement of immediately loaded implants, and limited information is available regarding loading directions and the associated in vivo characteristics of peri-implant bone during the early stages. This study aimed to investigate the effects of immediate loading directionality on the expression of mechanical sensing protein PIEZO1 and the healing process of peri-implant bone in the early stage. Methods Thirty-two implants were inserted into the goat iliac crest models with 10 N static lateral immediate loading applied, followed by histological, histomorphological, immunohistochemical, X-ray microscopy and energy dispersive X-ray spectroscopy evaluations conducted after 10 days. Results From evaluations at the cellular, tissue, and organ levels, it was observed that the expression of mechanical sensing protein PIEZO1 in peri-implant bone was significantly higher in the compressive side compared to the tensile side. This finding coincided with trends observed in interfacial bone extracellular matrix (ECM) contact percentage, bone mass, and new bone formation. Conclusions This study provides a novel insight into the immediate loading directionality as a potential influence factor for dental implant treatments by demonstrating differential effects on the mechanical sensing protein PIEZO1 expression and related early-stage healing processes of peri-implant bone. Immediate loading directions serve as potential therapeutic influence factors for peri-implant bone during its early healing stage.

Introduction Excessive osteoclastogenesis is a key driver of inflammatory bone loss. Suppressing osteoclastogenesis has always been considered essential for the treatment of inflammatory bone loss. N-acetyltransferase 10 (NAT10) is the sole enzyme responsible for N4-acetylcytidine (ac4C) modification of mRNA, and is involved in cell development. However, its role in osteoclastogenesis and inflammatory bone loss remained elusive. Objectives We aimed to clarify the regulatory mechanism of NAT10 and ac4C modification in osteoclastogenesis and inflammatory bone loss. Methods NAT10 expression and ac4C modification during osteoclastogenesis were determined by quantitative real-time PCR (qPCR), western blotting, dot blot and immunofluorescent staining, and the effect of NAT10 inhibition on osteoclast differentiation in vitro was measured by the tartrate-resistant acid phosphatase staining, podosome belts staining assay and bone resorption pit assay. Then, acRIP-qPCR and NAT10RIP-qPCR, ac4C site prediction, mRNA decay assay and luciferase reporter assay were performed to further study the underlying mechanisms. At last, mice models of inflammatory bone loss were applied to verify the therapeutic effect of NAT10 inhibition in vivo. Results NAT10 expression was upregulated during osteoclast differentiation and highly expressed in alveolar bone osteoclasts from periodontitis mice. Inhibition of NAT10 notably reduced osteoclast differentiation in vitro, as indicated by great reduction of tartrated resistant acid phosphatse positive multinuclear cells, osteoclast-specific gene expression, F-actin ring formation and bone resorption capacity. Mechanistically, NAT10 catalyzed ac4C modification of Fos (encoding AP-1 component c-Fos) mRNA and maintained its stabilization. Besides, NAT10 promoted MAPK signaling pathway and thereby activated AP-1 (c-Fos/c-Jun) transcription for osteoclastogenesis. Therapeutically, administration of Remodelin, the specific inhibitor of NAT10, remarkably impeded the ligature-induced alveolar bone loss and lipopolysaccharide-induced inflammatory calvarial osteolysis. Conclusions Our study demonstrated that NAT10-mediated ac4C modification is an important epigenetic regulation of osteoclast differentiation and proposed a promising therapeutic target for inflammatory bone loss.

Background Entirely impacted mandibular third molar (EIM3M) concerns the pathological external root resorption (ERR) of the adjacent mandibular second molar (M2M) and formation of granulation tissue between two molars. The study aimed to clarify the effect of αENaC, a mechano-sensitive molecule, to explore the mechanical mechanism in this scenario. Methods The force EIM3M exerted on M2M was proved by finite element analysis. αENaC expressions were tested by real-time polymerase chain reaction (PCR), immunoblotting and immunofluorescence. Inflammatory and epithelial-mesenchymal transition (EMT)-related molecules expressions were also detected by real-time PCR. The correlation was analyzed by Spearman’s correlation analysis, and receiver-operator characteristic (ROC) curve was further exhibited. Results The force was concentrated in the ERR area. αENaC was upregulated, positively correlated with ERR degree and localized to the fibroblasts in ERR granulation tissues. Moreover, αENaC was respectively and positively associated with elevated TNF-α and N-cadherin in ERR granulation tissues. More importantly, ROC analysis verified αENaC as a novel indication of the incidence of this disease. Conclusions Our finding revealed the force from EIM3M causing ERR of M2M, and elucidated the expression and localization of αENaC and its positive correlation with inflammation, EMT and disease severity, suggesting a novel indication in this disease.

BACKGROUND:Bile acids, as a group of cholesterol metabolites, play important roles in inflammation and bone metabolism. However, the possible link between bile acids and periodontitis is still unclear. This study aimed to clarify the alterations of the bile acid profile and corresponding receptor expression levels in periodontitis patients, and evaluate their association with periodontitis severity.METHODS:The concentrations of 15 bile acids in gingival tissues from 16 periodontitis patients and 16 healthy individuals were tested by metabolomics. Sphingosine-1-phosphate receptor 2 (S1PR2) expression was determined by real-time PCR and immunohistochemistry, which was also validated in two datasets, GSE16134 and GSE10334. The correlation between bile acids, S1PR2, and clinical parameters was analyzed by Spearman's correlation analysis, and receiver-operator characteristic (ROC) curves were examined to access the ability of bile acids and S1PR2 for defining local periodontitis status.RESULTS:In the periodontitis group, concentrations of total bile acids were elevated by increases of all bile acid forms, and five conjugated bile acids were significantly increased. Meanwhile, the expression of their receptor, S1PR2, was also upregulated in the periodontitis group. Positive correlations were further observed between glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), S1PR2, and periodontal clinical parameters. ROC analysis also showed combinations of two bile acids (GCA and TCDCA) with S1PR2 as novel signatures for indicating local periodontitis status.CONCLUSION:Our findings demonstrated the alterations of the bile acid profile and receptor S1PR2 expression in periodontitis patients, and provided evidence of association between bile acids and periodontitis status.

Although Vanins are closely related to neutrophil regulation and response to oxidative stress, and play essential roles in inflammatory diseases with clinical significance, their contribution to periodontitis remains to be determined. This research was designed to assess the expression of Vanins in human gingiva, and to define the relationship between Vanins and periodontitis. Forty-eight patients with periodontitis and forty-two periodontal healthy individuals were enrolled for gingival tissue sample collection. Expression levels of VNN1, VNN2 and VNN3 were evaluated by RT-qPCR and validated in datasets GSE10334 and GSE16134. Western blot and immunohistochemistry identified specific proteins within gingiva. The histopathological changes in gingival sections were investigated using HE staining. Correlations between Vanins and clinical parameters, PD and CAL; between Vanins and inflammation, IL1B; and between Vanins and MPO in periodontitis were investigated by Spearman's correlation analysis respectively. Associations between VNN2 and indicators of neutrophil adherence and migration were further validated in two datasets. Vanins were at higher concentrations in diseased gingival tissues in both RT-qPCR and dataset analysis (p < 0.01). Assessment using western blot and immunohistochemistry presented significant upregulations of VNN1 and VNN2 in periodontitis (p < 0.05). The higher expression levels of Vanins, the larger the observed periodontal parameters PD and CAL (p < 0.05), and IL1B (p < 0.001). Moreover, positive correlations existed between VNN2 and MPO, and between VNN2 and neutrophil-related indicators. Our study demonstrated upregulation of Vanins in periodontitis and the potential contribution of VNN2 to periodontitis through neutrophils-related pathological processes.

AbstractBackground and ObjectivePeriodontitis is a multifactorial chronic inflammatory disease that can lead to the irreversible destruction of dental support tissues. As an epigenetic factor, the expression of circRNA is tissue‐dependent and disease‐dependent. This study aimed to identify novel periodontitis‐associated circRNAs and predict relevant circRNA‐periodontitis regulatory network by using recently developed bioinformatic tools and integrating sequencing profiling with clinical information for getting a better and more thorough image of periodontitis pathogenesis, from gene to clinic.Material and MethodsHigh‐throughput sequencing and RT‐qPCR were conducted to identify differentially expressed circRNAs in gingival tissues from periodontitis patients. The relationship between upregulated circRNAs expression and probing depth (PD) was performed using Spearman's correlation analysis. Bioinformatic analyses including GO analysis, circRNA‐disease association prediction, and circRNA‐miRNA‐mRNA network prediction were performed to clarify potential regulatory functions of identified circRNAs in periodontitis. A receiver‐operating characteristic (ROC) curve was established to assess the diagnostic significance of identified circRNAs.ResultsHigh‐throughput sequencing identified 70 differentially expressed circRNAs (68 upregulated and 2 downregulated circRNAs) in human periodontitis (fold change >2.0 and p < .05). The top five upregulated circRNAs were validated by RT‐qPCR that had strong associations with multiple human diseases, including periodontitis. The upregulation of circRNAs were positively correlated with PD (R = .40–.69, p < .05, moderate). A circRNA‐miRNA‐mRNA network with the top five upregulated circRNAs, differentially expressed mRNAs, and overlapped predicted miRNAs indicated potential roles of circRNAs in immune response, cell apoptosis, migration, adhesion, and reaction to oxidative stress. The ROC curve showed that circRNAs had potential value in periodontitis diagnosis (AUC = 0.7321–0.8667, p < .05).ConclusionCircRNA‐disease associations were predicted by online bioinformatic tools. Positive correlation between upregulated circRNAs, circPTP4A2, chr22:23101560‐23135351+, circARHGEF28, circBARD1 and circRASA2, and PD suggested function of circRNAs in periodontitis. Network prediction further focused on downstream targets regulated by circRNAs during periodontitis pathogenesis.

The tilted implant with immediate function is increasingly used in clinical dental therapy for edentulous and partially edentulous patients with excessive bone resorption and the anatomic limitations in the alveolar ridge. However, peri-implant cervical bone loss can be caused by the stress shielding effect. Herein, inspired by the concept of “materiobiology”, the mechanical characteristics of materials were considered along with bone biology for tilted implant design. In this study, a novel Ti–35Nb–2Ta–3Zr alloy (TNTZ) implant with low elastic modulus, high strength and favorable biocompatibility was developed. Then the human alveolar bone environment was mimicked in goat and finite element (FE) models to investigate the mechanical property and the related peri-implant bone remodeling of TNTZ compared to commonly used Ti–6Al–4V (TC4) in tilted implantation under loading condition. Next, a layer-by-layer quantitative correlation of the FE and X-ray Microscopy (XRM) analysis suggested that the TNTZ implant present better mechanobiological characteristics including improved load transduction and increased bone area in the tilted implantation model compared to TC4 implant, especially in the upper 1/3 region of peri-implant bone that is “lower stress”. Finally, combining the static and dynamic parameters of bone, it was further verified that TNTZ enhanced bone remodeling in “lower stress” upper 1/3 region. This study demonstrates that TNTZ is a mechanobiological optimized tilted implant material that enhances load transduction and bone remodeling.

锁会降低咀嚼效能,影响容貌外观.伴有牙周炎症与牙槽骨吸收的锁病例会增加临床治疗难度.为了探讨复杂的成人单侧后牙锁患者的种植治疗方法,在牙周治疗与拔牙位点保存的基础上行种植手术,采用种植体表面成形术、GBR和角化龈增量手术处理种植体周炎,最终实现种植体支持的固定修复.种植修复半年后复查,T-scan显示咬合能力恢复,修复效果稳定.对于成人单侧后牙锁患者行种植固定修复是一种有效的治疗手段,需要充分考虑软硬组织风险,定期维护种植体周组织健康.

In order to investigate the deterioration of microstructure in service, the intrinsic microstructural stability and performance of DD6 during long-term aging without an external load are investigated. During aging at 980°C, γ′ rafting in 〈100〉 and 〈010〉 directions show no anisotropy due to small driving forces. γ′ coarsening and rafting lead to a monotonic decrease in hardness between 200 and 1000 h. However, precipitation of topologically close-packed (TCP) phases occurs significantly during aging at 1050°C. The amount of TCP phases increases initially, and then almost saturates, which results in a decrease in hardness. However, owing to the reduction in the growth of the TCP phases and coarsening of γ′, the hardness saturates for an aging time greater than 500 h.

Objectives This study aimed to clarify the expression profile and significance of lipoxygenases in periodontitis. Materials and Methods The mRNA levels of lipoxygenases in gingival tissues from 14 patients with periodontitis and 14 healthy individuals were determined by real-time PCR, and validated in datasets, and , and by Western blotting. Correlation of differentially expressed lipoxygenases with clinical parameters and expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta, matrix metalloproteinase (MMP)-8, MMP-9, and receptor activator of nuclear factor-kappa B ligand (RANKL) was investigated in patients with periodontitis by Spearman's correlation analysis. Results The expression of ALOX5 (2.1-fold,p < .05), ALOX12B (2.9-fold,p < .001), and ALOX15B (9.4-fold,p < .001) was upregulated in gingival tissues from patients with periodontitis, which was validated by dataset analysis and Western blotting. Positive correlations were observed between ALOX5 and probing depth, and ALOX15B and probing depth and clinical attachment loss. Furthermore, ALOX5 expression was positively correlated with TNF-alpha, MMP-8, MMP-9, and RANKL expression, and ALOX15B was positively correlated with MMP-8 and RANKL. Conclusions Our findings indicated the upregulation of ALOX5 and ALOX15B in periodontitis and suggested that ALOX5 and ALOX15B may be involved in periodontitis pathogenesis, including inflammation, connective tissue destruction, and abnormal bone metabolism.

Effect of solution treatment on the micropore and mechanical properties is investigated for the DD6 superalloy. The results show that solution treatment has positive and negative effects on the DD6 superalloy, which can weaken the segregation significantly. After solution treatment, the segregation ratio of the major alloying elements tends to 1. However, the amount of micropores increases with increasing solutionising time and can reach 0.46%, which is one order of magnitude higher than that of the as-cast superalloy. The hardness increases slightly, especially for the superalloy solutionised at 1310°C with a 5% increase in hardness compared to the as-cast superalloy. Hardness, tensile and stress rupture properties of the DD6 superalloy can reach the best after solution treatment at 1310°C and 4 h.

目的 调查下颌第三磨牙生长情况的对称性及其对相邻第二磨牙远中邻面龋患病情况的影响,为临床早期预防性拔除下颌智齿提供依据.方法 纳入2019年11月1日至2019年11月23日在上海交通大学医学院附属仁济医院口腔科拍摄的全景片196张,调查其双侧下颌第三磨牙的对称性,通过卡方检验分析不同阻生类型的下颌第三磨牙与相邻第二磨牙远中邻面龋患病情况之间的关系.结果 双侧下颌第三磨牙对称者187例,占比95.41％.Winter分类中垂直阻生对称性(79.2％)显著高于近中阻生(47.6％)与水平阻生(59.1％)(P=0.001);Winter分类为近中阻生(46.4％)和水平阻生(38.4％)的下颌第三磨牙,其相邻第二磨牙远中邻面龋发生率显著高于垂直阻生(23.6％)(P=0.001).结论 下颌智齿具有对称性;为预防相邻第二磨牙远中邻面龋,近中阻生及水平阻生的下颌第三磨牙应在临床上早期预防性拔除.

This study investigates the inner quality including microdefects, orientation deviation and dendrite spacing of DD6 single-crystal superalloy with different drawing velocities. The XRD, SEM, electron probe microanalyzer methods and mechanical properties were used to evaluate the defects and microstructures, related to their evolution mechanism in DD6 superalloy. It was found that the drawing velocity of 80 μm/s can obtain a 4° deviation angle from the 〈001〉 orientation, less microdefects and well tensile properties. With drawing velocity increasing from 30 to 150 μm/s, PDAS decreases from 471 to 359 μm, respectively. Moreover, the shrinkage porosity decreases firstly and then increases due to different feeding conditions. In addition, the segregation of the solute elements increases and promotes the content of γ/γ′ eutectic, which deteriorate the mechanical properties. The research results can provide a basis for the development of high-quality single-crystal blades.

Objective To summarise the lessons learned from implementing a dental undergraduate research programme over the past eleven years and identify key elements to guarantee the success of dental undergraduate research in the future. Material and Methods An overview of 80 research projects from 2007 to 2017 was provided, consisting of 239 participating undergraduates and 47 faculty advisors. Students' academic performance was compared between participating and non-participating undergraduates. An anonymous questionnaire was designed and distributed to participants, with VAS satisfaction assessment, Likert-scale items and open-ended questions. Questions focused on overall satisfaction, motivation, benefits to student career development and essential elements for the dental undergraduate research programme in the future. Results The undergraduate participants had significantly better scores of GPAs (3.41 vs 3.21;P < 0.0001), obtained more awards on the honour rolls (0.53 vs 0.30;P = 0.0171) and published more peer-reviewed articles (1.62 vs 1.31;P = 0.0253) than non-participants. Seventy-two undergraduates (75.79%) and thirty-eight advisors (80.85%) responded to the questionnaire. The overall satisfaction was scored as 78.18/100 and 72.36/100 amongst advisors and students, respectively. Interest was considered the best motivation for participation by students (3.81/5.00) and advisors (4.00/5.00). The research programme was beneficial to students' overall career development. Essential roles played by the dental school, faculty and undergraduates were suggested to improve the research environment. Conclusion The dental undergraduate research programme has positive effects on students' academic performance. The support of the dental school, the engagement of qualified faculty, the interest and autonomy of students and camaraderie amongst these three key elements are essential for the research programme in the future.

Bone tissue engineering has substantial potential for the treatment of massive bone defects; however, efficient vascularization coupled with bone regeneration still remains a challenge in this field. In the current study,supercritical carbon dioxide (scCO2) foaming technique was adopted to fabricate mesoporous bioactive glasses (MBGs) particle-poly (lactic-co-glycolic acid) (PLGA) composite scaffolds with appropriate mechanical and degradation properties as well as in vitro bioactivity. The MBG-PLGA scaffolds incorporating the bioactive lipid FTY720 (designated as FTY/MBG-PLGA) exhibited simultaneously sustained release of thebioactive lipid and ions. In addition to providing a favorable microenvironment for cellular adhesion and proliferation, FTY/MBG-PLGA scaffolds significantly facilitated the in vitro osteogenic differentiation of rBMSCs and also markedly stimulated the up regulation of Hif-1α expression via the activation of the Erk1/2 pathway, which mediated the osteogenic and pro-angiogenic effects on rBMSCs. Furthermore, FTY/MBG-PLGA extracts induced superior in vitro angiogenic performance of HUVECs. In vivo evaluation of critical-sized rat calvarial bone defects indicated that FTY/MBG-PLGA scaffolds potently promoted vascularized bone regeneration. Notably, the significantly enhanced formation of type Hvessels (CD31hiEmcnhineo-vessels) was observed in newly formed bone tissue in FTY/MBG-PLGA group, strongly suggesting that FTY720 and therapeutic ions released from the scaffolds synergistically induced moretype H vessel formation, which indicated the coupling of angiogenesis and osteogenesis to achieve efficiently vascularized bone regeneration. Overall,the results indicated that the foamed porous MBG-PLGA scaffolds incorporating bioactive lipids achieved desirable vascularization-coupled bone formation and could be a promising strategy for bone regenerative medicine.