Cancer cell membrane camouflaging mesoporous nanoplatform interfering with cellular redox homeostasis to amplify photodynamic therapy on oral carcinoma.

The efficacy of photodynamic therapy (PDT) is still limited by the inefficient utilisation of generated ROS in tumours due to cellular redox homeostasis. To improve the therapeutic efficacy for oral carcinoma, biomimetic cell membrane-coated mesoporous nanoplatform was tailored to interfere with cellular redox homeostasis for amplified PDT. In this study, CAL-27 cancer cell membrane (CM) was encapsulated onto the mesoporous silica NPs (MSN), which were preloaded with Chlorin e6 (Ce6) and Curcumin (Cur). The biomimetic nanoparticles displayed a size of around 120 nm, which had excellent cytotoxicity under a laser and increased uptake ability to tumour cell. After internalised by cancer cells, the released Cur could effectively disturb ROS-defence system by suppressing TrxR activity, and decreasing TrxR-2 expression (p < 0.05), leading to enhanced cancer cell killing ability of PDT. The biomimetic system was found to selectively accumulate in the tumour due to its homologous targeting capability and inhibit tumour growth significantly. In a word, the biomimetic nanoplatform apparently enhanced the therapeutic effect of PDT on tumours by Cur disturbing the ROS-defence system, which exhibited a new way to enhance PDT.

Stress response in periodontal ligament stem cells may contribute to bisphosphonate­associated osteonecrosis of the jaw: A gene expression array analysis.

Gene expression alterations in periodontal ligament stem cells (PDLSCs) during bisphosphonate (BP) usage and the transcriptomic mechanism underlying BP­related osteonecrosis of the jaw have not been fully elucidated. In the present study, human PDLSCs were isolated from adults with no history of periodontal disease, and subsequently incubated and treated with zoledronate on days 3 and 5. Subsequently, PDLSCs from all timepoints were screened using an Affymetrix Gene Expression Array. Limma differential expression analysis was performed on a normalized gene expression matrix, followed by cluster analysis, pathway and network analyses. Overall, 906 genes (352 upregulated and 554 downregulated) exhibited differential expression levels between days 0 and 5, and these were termed slow­response genes. These slow­response genes were enriched in cellular stress response signaling pathways (upregulated genes), as well as proliferation­ and ossification­associated signaling pathways (downregulated genes). Furthermore, 168 (day 3 vs. 0) and 105 (day 5 vs. 3) genes were differentially expressed between adjacent timepoints. These genes were also enriched in stress response­ and proliferation­associated signaling pathways, but not in ossification­associated signaling pathways. Poly(ADP­ribose) polymerase 1 (PARP1) and CYLD lysine 63 deubiquitinase (CYLD) had the most protein­protein interaction partners among the slow­response genes and were connected with both stress­ (e.g. caspase­1) and ossification­associated genes [e.g. secreted phosphoprotein 1 and collagen type I α1 chain (COL1A1)]. BP treatment induced stress response­like transcriptional alterations in PDLSCs, followed by inhibition of proliferation and ossification. These alterations may contribute to the onset of jaw osteonecrosis. PARP1 and CYLD may be two key genes involved in this pathological procedure.

Surface Modification of ZrO2 Nanoparticles and Its Effects on the Properties of Dental Resin Composites.

Endowing dental resin composites (DRCs) with suitable radiopacity is necessary for clinical diagnosis during treatment of caries. To reach this effect, ZrO2 nanoparticles were introduced into the DRCs in this work after modification with two different methods, one modified with 3-methacryloxypropyltrimethoxysilane (ZrO2@γ-MPS) and the other coated with mesoporous SiO2 and then modified with γ-MPS (ZrO2@m-SiO2@γ-MPS). These ZrO2 nanoparticles were used as functional additives, and the SiO2 nanoparticles were used as the fundamental filler in the preparation of DRCs to study the effects of the surface modification of ZrO2 nanoparticles and the amount of particles added (0, 3, 5, and 7 wt %) on the properties of the DRCs. The DRC containing ZrO2@m-SiO2@γ-MPS showed a higher transmittance, which may be attributed to the fact that the SiO2 coating reduced the refractive index of the nanoparticles and thus decreased the scattering of light within the DRC. The silane polymer film on the surface of ZrO2@γ-MPS nanoparticles acted as a lubricant and decreased the viscosity of DRC, but the DRC containing ZrO2@m-SiO2@γ-MPS showed a higher viscosity due to the presence of a mesoporous structure. The radiopacity value of the DRCs containing the functional additives was close to 1 mm Al, much higher than that of the DRC filled with SiO2 nanoparticles alone (0.74 ± 0.07 mm Al), meeting the requirement of ISO 4049:2009. The surface modification of ZrO2 nanoparticles had no significant influence on the mechanical properties, radiopacity, and cytotoxicity of DRCs (p > 0.05). This study provides useful insight into the design and development of radiopaque DRCs with excellent physical and mechanical properties.

Decreased Osteogenic Ability of Periodontal Ligament Stem Cells Leading to Impaired Periodontal Tissue Repair in BRONJ Patients.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe adverse reaction, which results in progressive bone destruction in the maxillofacial region of patients. To date, the pathological mechanisms remain largely unclear. Recently, we found that BRONJ patient had significantly deep periodontal pockets and severe periodontal bone defects before the exposed necrotic bone. Human periodontal ligament stem cells (hPDLSCs) play key roles in physiological maintenance and regeneration of periodontal tissues. However, the activities of hPDLSCs derived from BRONJ lesions and the role of hPDLSCs in BRONJ periodontal defect repair remain poorly understood. The aim of the present study was to elucidate the role of hPDLSCs in BRONJ. In this study, we found that the capacities of cell proliferation, adhesion, and migration of hPDLSCs derived from BRONJ lesions (BRONJ-hPDLSCs) were significantly decreased compared with control-hPDLSCs. BRONJ-hPDLSCs underwent early apoptosis compared with control-hPDLSCs. Importantly, we first demonstrated that BRONJ-hPDLSCs exhibited impaired osteogenic differentiation abilities in ectopic osteogenesis of nude mice. The above results suggested that the impaired BRONJ-hPDLSCs may be an important factor in deficient periodontal repair of BRONJ lesions and provide new insight into the underlying mechanism of BRONJ.

Dental Resin Composites Reinforced by Rough Core-Shell SiO2 Nanoparticles with a Controllable Mesoporous Structure.

A porous structure within filler particles may improve interfacial bonding between the resin matrix and fillers for the preparation of dental resin composites (DRCs). In this study, rough core-shell SiO2 (rSiO2) nanoparticles with controllable mesoporous structures were synthesized via an oil-water biphase reaction system and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and N2 adsorption-desorption measurements. The influence of the mesoporous shell thickness of rSiO2 and mass ratio between rSiO2 and smooth SiO2 (sSiO2) on the physical and mechanical properties of DRCs was studied. The rSiO2 with a thin mesoporous shell could form a strong physical interlocking with the resin matrix, which improved the mechanical properties with the exception of flexural modulus. The mechanical properties were further optimized by mixing rSiO2 and sSiO2. The flexural strength and compressive strength of the DRC at a mass ratio of 5:5 increased by 24.3% and 16.8%, respectively, compared with the DRC filled with sSiO2 alone. There is no statistically significant difference in the flexural modulus between these two DRCs (p > 0.05). The DRCs in this study showed excellent biocompatibility on the human dental pulp cells (HDPCs) as demonstrated by the cytotoxicity tests. The use of rSiO2 provides a promising approach to develop strong, durable, and biocompatible DRCs.

Strong antibacterial dental resin composites containing cellulose nanocrystal/zinc oxide nanohybrids.

OBJECTIVE: The aim is to explore the reinforcing and antibacterial effect of cellulose nanocrystal/zinc oxide (CNC/ZnO) nanohybrids on dental resin composites (DRCs). METHODS: CNC/ZnO nanohybrids were prepared through precipitating Zn2+ on the surface of CNC and then introduced into the DRCs. The mechanical properties of DRCs including compressive strength, flexural modulus, flexural strength, and Vickers microhardness were characterized. The antibacterial activity of DRCs to Streptococcus mutans was determined and the morphology of Streptococcus mutans on the surface of DRCs after incubation was observed. The morphology of fractured surface after flexural test and Zn content in DRCs were analyzed. RESULTS: Compared with DRCs without CNC/ZnO nanohybrids, DRCs containing 2 wt.% CNC/ZnO nanohybrids possess higher compressive strength and flexural modulus and there is no significantly statistical difference (P＞0.05) on the flexural strength and Vickers microhardness. The excess use of CNC/ZnO nanohybrids decreases the mechanical properties of DRCs except flexural modulus. DRCs containing CNC/ZnO nanohybrids show excellent antibacterial properties and a 78% reduction in bacterial number is obtained when 2% CNC/ZnO nanohybrids are added. CONCLUSION: The small amounts of CNC/ZnO nanohybrids have a positive influence on the mechanical and antibacterial properties of DRCs. SIGNIFICANCE: The prepared DRCs are promising to address bulk fracture and secondary caries.

Synthesis of core-shell structured ZnO@m-SiO2 with excellent reinforcing effect and antimicrobial activity for dental resin composites.

OBJECTIVE: The aim of this study is to explore the reinforcing effect and the antimicrobial activity of the core-mesoporous shell structured ZnO@m-SiO2, which possesses the micromechanical resin matrix/filler interlocking in dental composites, and to investigate the effect of filler compositions on their physical-mechanical properties. METHODS: ZnO@m-SiO2 was synthesized by a simple self-assembly method and then characterized by electron microscopy, X-ray diffraction (XRD) and N2 adsorption/desorption measurements. Mechanical properties of dental composites reinforced with ZnO@m-SiO2 and nonporous SiO2 particles were measured with a universal mechanical testing machine. Fracture morphologies of these composites were observed by field-emission scanning electron microscopy (FE-SEM), and their antimicrobial activities were evaluated according to the ASTM E 2180-07 (2012) method. Resin composites containing unimodal silanized SiO2 were served as the control group. RESULTS: The impregnation of lower loading of ZnO@m-SiO2 (≤7wt%) into dental composites including silanized SiO2 substantially increased their mechanical properties. Among all composites, the optimal composite Z7S63 (ZnO@m-SiO2: silanized SiO2=7:63, wt/wt, total filler loading 70wt%) demonstrated the best flexural strength, flexural modulus and compression strength, which were increased by 121.2, 67.1 and 32.5%, respectively, in comparison with the control composite Z0S70. In addition, this optimal composite also exhibited superior antimicrobial activity (>99.9%) and acceptable degree of conversion, polymerization shrinkage and curing depth. SIGNIFICANCE: The incorporation of ZnO@m-SiO2 and silanized SiO2 as bimodal fillers led to the design and formulation of dental composites with excellent comprehensive performance, especially the improved mechanical properties and the superior antimicrobial activity.

Comparison of different grafting materials for treatment of bone defect distal to the molar in canine.

BACKGROUND: The extraction of impacted mandibular 3rd molar is highly related to bone defect distal to the adjacent 2nd molar. PURPOSE: The aim of this study was to evaluate the effect of different grafting materials for the treatment of bone defect distal to the mandibular molar in canine model. MATERIALS AND METHODS: In 12 beagle dogs, bilateral mandibular 2nd and 3rd molars were extracted and entire mesial bone of the 2nd molar extracted socket was surgically removed. Twenty-four bone defects (4 mm width and 8 mm depth) were randomly assigned to 4 groups, and grafted using 1 of the following protocols: (1) group C: no graft; (2) group Ta: autogenous bone (AB); (3) group Tb: deproteinized bovine bone mineral (DBBM) with a collagen membrane (CM); and (4) group Tab: an equal mixture of AB/DBBM + CM. Quantitative imageology analyses using micro-CT and fluorescence microscopy, as well as qualitative analyses using histological and histomorphometric evaluations, were characterized at postoperative 12 weeks. Significant differences of all variables were tested by multivariate analysis (P < .05). RESULTS: The defect depth was significantly lower in groups Ta, Tb, and Tab (1.70, 1.97, and 1.61 mm, respectively; mean) than in the group C (3.66 mm, P < .01, all). Compared to the sites received DBBM/CM, sites grafted with AB or AB/DBBM exhibited significant greater and faster new bone formation (P < .01). The percentage of DBBM remnants area (%) was significantly higher in group Tb than in group Tab (10.43% and 1.13%, P < .01; mean). CONCLUSIONS: Our data suggested grafting AB alone, DBBM/CM, or AB/DBBM/CM resulted in similar periodontal parameters in canine. Furthermore, the AB could accelerate new bone regeneration and mineralization, and promote the biodegradation of DBBM.

Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect.

Repair of large bone defects remains a challenge for surgeons, tissue engineering represents a promising approach. However, the use of this technique is limited by delayed vascularization in central regions of the scaffold. Growth differentiation factor 15(GDF15) has recently been reported to be a potential angiogenic cytokine and has an ability to promote the proliferation of human umbilical vein endothelial cells(HUVECs). Whether it can be applied for promoting vascularized bone regeneration is still unknown. In this study, we demonstrated that GDF15 augmented the expression of cyclins D1 and E, induced Rb phosphorylation and E2F-1 nuclear translocation, as well as increased HUVECs proliferation. Furthermore, we also observed that GDF15 promoted the formation of functional vessels at an artificially-induced angiogenic site, and remarkably improved the healing in the repair of critical-sized calvarial defects. Our results confirm the essential role of GDF15 in angiogenesis and suggest its potential beneficial use in regenerative medicine.