The association between clinical diagnostic factors and the prevalence of vertical root fracture in endodontic surgery.

BACKGROUND/PURPOSE: Diagnosis of vertical root fractures (VRFs) can often be challenging due to the similarity of signs and symptoms with other common dental infectious diseases. This study was aimed at evaluating the potential relationship between VRFs and commonly used clinical diagnostic factors. METHODS: 330 root-filled teeth with endodontic failures were subjected to endodontic microsurgery over a six-year period. VRFs were identified in 61 teeth. A randomly age- and sex-matched retrospective case-control study was conducted on a subset of 59 root-filled teeth with VRFs (cases) and 177 root-filled teeth without VRFs (controls). The strength of association between preoperative signs and radiographic findings and VRFs was evaluated using logistic regression model. RESULTS: Sinus tract, periodontal pocket depth ≥5 mm, periodontal swelling or abscess, and radiological image of J-shaped or "halo" radiolucency were significantly more frequent in cases than in controls (p < 0.05). With regard to logistic regression analysis, J-shaped or "halo" radiolucency demonstrated the greatest association with VRF, followed by periodontal pocket depth ≥5 mm, sinus tract, and periodontal swelling or abscess. Approximately 70% of cases manifested themselves as combinations of at least two of these factors. Teeth having two and three or four of these factors had 3.14 times and 11.64 times higher risks for the presentations of VRFs, respectively (p < 0.001). CONCLUSION: The major risk for VRFs was represented by those presenting radiological image of J-shaped or "halo" radiolucency, periodontal pocket depth ≥5 mm, sinus tract, and periodontal swelling or abscess simultaneously.

Fabrication of multicomponent polymer nanostructures containing PMMA shells and encapsulated PS nanospheres in the nanopores of anodic aluminum oxide templates.

Multi-component polymer nanomaterials have attracted great attention because of their applications in areas such as biomedicine, tissue engineering, and organic solar cells. The precise control over the morphologies of multi-component polymer nanomaterials, however, is still a great challenge. In this work, the fabrication of poly(methyl methacrylate)(PMMA)/poly-styrene (PS) nanostructures that contain PMMA shells and encapsulated PS nanospheres is studied. The nanostructures are prepared using a triple solution wetting method with anodic aluminum oxide (AAO) templates. The nanopores of the templates are wetted sequentially by PS solutions in dimethylformamide (DMF), PMMA solutions in acetic acid, and water. The compositions and morphologies of the nanostructures are controlled by the interactions between the polymers, solvents, and AAO walls. This work not only presents a feasible method to prepare multi-component polymer nanomaterials, but also leads to a better understanding of polymer-solvent interactions in confined geometries.

An investigation of water status in gelatin methacrylate hydrogels by means of water relaxometry and differential scanning calorimetry.

The relationship between molecular structure and water dynamics is a fundamental yet often neglected subject in the field of hydrogels for drug delivery, bioprinting, as well as biomaterial science and tissue engineering & regenerative medicine (TE&RM). Water is a fundamental constituent of hydrogel systems and engages via hydrogen bonding with the macromolecular network. The methods and techniques to measure and reveal the phenomena and dynamics of water within hydrogels are still limited. In this work, differential scanning calorimetry (DSC) was used as a quantitative method to analyze freezable (including free and freezable bound) and non-freezable bound water within gelatin methacrylate (GelMA) hydrogels. Nuclear magnetic resonance (NMR) is a complementary method for the study of water behavior and can be used to measure the spin-relaxation of water hydrogen nuclei, which is related to water dynamics. In this research, nuclear magnetic resonance relaxometry was employed to investigate the molecular state of water in GelMA hydrogels using spin-lattice (T1) and spin-spin (T2) spin-relaxation time constants. The data displays a trend of increasing bound water content with increasing GelMA concentration. In addition, T2 values were further applied to calculate microviscosity and translational diffusion coefficients. Water relaxation under various chemical environments, including different media, temperatures, gelatin sources, as well as crosslinking effects, were also examined. These comprehensive physical data sets offer fundamental insight into biomolecule transport within the GelMA hydrogel system, which ultimately are important for drug delivery, bioprinting, as well as biomaterial science and TE&RM communities.

Effect of nonsolvent on the formation of polymer nanomaterials in the nanopores of anodic aluminum oxide templates.

We study the effect of nonsolvent on the formation of polymer nanomaterials in the nanopores of porous templates. Water (nonsolvent) is added into a poly (methyl methacrylate) (PMMA) solution in dimethylformamide (DMF) confined in the nanopores of an anodic aluminum oxide (AAO) template. Water forms a wetting layer on the pore wall and causes the PMMA solution to be isolated in the center of the nanopore, resulting in the formation of PMMA nanospheres or nanorods after the solvent is evaporated. The formation of the polymer nanomaterials induced by nonsolvent is found to be driven by the Rayleigh-instability-type transformation. Without adding the nonsolvent, PMMA chains precipitate on the walls of the nanopores after the solvent is evaporated, and PMMA nanotubes are obtained.

Measurements of craniofacial morphology using photogrammetry in children with sleep-disordered breathing.

OBJECTIVE: To assess the craniofacial morphology in children with sleep-disordered breathing (SDB) using nonradiation and readily accessible photogrammetry technique. METHODS: Included children aged 3-18 years with SDB-related symptoms from April 2019 to February 2020 in a tertiary center. All participants underwent craniofacial photogrammetry and overnight polysomnography (PSG). Participants were stratified into 2 groups (obstructive sleep apnea [OSA] group: apnea-hypopnea index [AHI] ≥ 1 and non-OSA group: AHI <1). Craniofacial photogrammetry was performed to derive variables of craniofacial features in standardized frontal and profile views. The 2 groups were propensity score matched based on age, sex, and body mass index (BMI) percentiles. Associations between craniofacial feature variables and OSA (AHI ≥1) likelihood were examined using logistic regression test. intraclass correlation coefficient (ICC) was used to evaluate the intrarater and interrater reliability. RESULTS: In total, 58 children were enrolled for the analysis after matching. All 3 variables representing the mandibular plane angle in the profile view were increased in the OSA group (mego-tn: 34.85 ± 5.99 vs 31.65 ± 5.96°, odds ratio [OR]: 1.10, 95% CI:1.02 to 1.18, P = .01; tn-gogn: 28.65 ± 6.38 vs 25.91 ± 5.38°, OR: 1.08, 95% CI:1.02 to 1.15, P = .012; and gome-tsup: 26.71 ± 6.13 vs 22.20 ± 5.89°, OR: 1.13, 95% CI:1.04 to 1.23, P = .003). CONCLUSIONS: Craniofacial photogrammetry revealed increased mandibular inclination in children with OSA. A steep mandibular plane with craniofacial photogrammetry is considered a potential predictor of pediatric OSA. Further investigation with a large sample size is required to clarify the validity of photogrammetry in evaluating pediatric OSA.

Poly(glycerol sebacate)-co-poly(ethylene glycol)/Gelatin Hybrid Hydrogels as Biocompatible Biomaterials for Cell Proliferation and Spreading.

Synthetic polymers have been widely employed to prepare hydrogels for biomedical applications, such as cell culture, drug delivery, and tissue engineering. However, the activity of cells cultured in the synthetic polymer-based hydrogels faces the challenges of limited cell proliferation and spreading compared to cells cultured in natural polymer-based hydrogels. To address this concern, a hybrid hydrogel strategy is demonstrated by incorporating thiolated gelatin (GS) into the norbornene-functionalized poly (glycerol sebacate)-co-polyethylene glycol (Nor_PGS-co-PEG, NPP) network to prepare highly biocompatible NPP/GS_UV hydrogels after the thiol-ene photo-crosslinking reaction. The GS introduces several desirable features (i.e., enhanced water content, enlarged pore size, increased mechanical property, and more cell adhesion sites) to the NPP/GS_UV hydrogels, facilitating the cell proliferation and spreading inside the network. Thus, the highly biocompatible NPP/GS_UV hydrogels are promising materials for cell encapsulation and tissue engineering applications. Taken together, the hybrid hydrogel strategy is demonstrated as a powerful approach to fabricate hydrogels with a highly friendly environment for cell culture, expanding the biomedical applications of hydrogels.

In situ formation of nanocomposite double-network hydrogels with shear-thinning and self-healing properties.

Nanocomposite double-network hydrogels (ncDN hydrogels) are recently introduced to address the limitations of traditional DN hydrogels, such as the lack of diversity in the network structure and the restricted functionalities. However, two challenges remain, including the time-consuming preparation and the lack of shear-thinning and self-healing properties. Here, our approach to developing versatile ncDN hydrogels is through the use of multiple interfacial crosslinking chemistries (i.e., noncovalent interactions of electrostatic interaction and hydrogen bonds as well as dynamic covalent interactions of imine bonds and boronate ester bonds) and surface functionalized nanomaterials (i.e. phenylboronic acid modified reduced graphene oxide (PBA-rGO)). PBA-rGO was used as a multivalent gelator to further crosslink the two polymer chains (i.e. triethylene glycol-grafted chitosan (TEG-CS) and polydextran aldehyde (PDA)) in DN hydrogels, forming the TEG-CS/PDA/PBA-rGO ncDN hydrogels in seconds. The microstructures (i.e. pore size) and properties (i.e. rheological, mechanical, and swelling properties) of the ncDN hydrogels can be simply modulated by changing the amount of PBA-rGO. The dynamic bonds in the polymeric network provided the shear-thinning and self-healing properties to the ncDN hydrogels, allowing the hydrogels to be injected and molded into varied shapes as well as self-repair the damaged structure. Besides, the designed TEG-CS/PDA/PBA-rGO ncDN hydrogels were cytocompatible and also exhibited antibacterial activity. Taken together, we hereby provide a nanomaterial approach to fabricate a new class of ncDN hydrogels with tailorable networks and favorite properties for specific applications.

Formation of highly elastomeric and property-tailorable poly(glycerol sebacate)-co-poly(ethylene glycol) hydrogels through thiol-norbornene photochemistry.

Poly(glycerol sebacate) (PGS) is a synthetic biorubber that presents good biocompatibility, excellent elasticity and desirable mechanical properties for biomedical applications; however, the inherent hydrophobicity and traditional thermal curing of PGS restrict its use in the fabrication of hydrogels for advanced bioapplications. Here, we designed a new class of hydrophilic PGS-based copolymers that allow hydrogel formation through thiol-norbornene chemistry. Poly(glycerol sebacate)-co-polyethylene glycol (PGS-co-PEG) macromers were synthesized through a stepwise polycondensation reaction, and then the norbornene functional groups were introduced to the PGS-co-PEG structure to form norbornene-functionalized PGS-co-PEG (Nor_PGS-co-PEG). Nor_PGS-co-PEG macromers can be crosslinked using dithiols to prepare hydrogels in the presence of light and photoinitiators. The mechanical, swelling and degradation properties of Nor_PGS-co-PEG hydrogels can be controlled by altering the crosslinker amount. In particular, the elongation of Nor_PGS-co-PEG hydrogels can be modulated up to 950%. Nor_PGS-co-PEG can be processed using electrospinning and 3D printing techniques to generate microfibrous scaffolds and printed structures, respectively. In addition, the cytocompatibility of Nor_PGS-co-PEG was also demonstrated using in vitro cellular viability studies. These results indicate that Nor_PGS-co-PEG is a promising biomaterial with definable properties for scaffold manufacturing, presenting a great potential for biomedical applications.

Analysis of clinical associated factors of vertical root fracture cases found in endodontic surgery.

BACKGROUND/PURPOSE: Early diagnosis of vertical root fracture (VRF) has been a great challenge. Since there is no single specific etiology identified, prevention of VRFs in endodontically treated teeth is quite difficult. The study aimed to evaluate the clinical associated factors of VRFs. MATERIALS AND METHODS: A retrospective observational study of medical charts was conducted in the Department of Endodontics of Taipei Medical University Hospital in Taiwan from January 2012 to July 2018. Logistic regression model was performed to determine the association between VRF and its clinical associated factors, inclusive of the tooth characteristics (age, gender and tooth type) and iatrogenic risk factors (history of root canal treatment, restoration and post). RESULTS: A total of 359 teeth were included in the study. The prevalence of VRF on a tooth basis was 18.7%. The result showed that age of more than 50 years (adjusted OR = 3.20, 95% CI: 1.81-5.64, p < 0.001) had significant higher risk of VRFs than those of less than 50 years. The subjects of molars (adjusted OR = 4.31; 95%CI = 2.24-8.27; P value < 0.001) and premolars (adjusted OR = 2.61; 95%CI = 1.16-5.86; P value = 0.021) had significant higher risk of VRFs than those of incisors. However, other variables such as gender, history of root canal treatment, restoration and post had no significant association with the VRF. CONCLUSION: Age and tooth type are significant clinical associated factors of VRF. In the presence of these factors as well as predominant diagnostic factors, clinical practitioners should be aware of the possible diagnosis of VRFs.

IL-1ß-induced MCP-1 expression and secretion of human dental pulp cells is related to TAK1, MEK/ERK, and PI3K/Akt signaling pathways.

OBJECTIVE: Interleukin-1ß (IL-1ß) is an inflammatory molecule of the dental pulp. IL-1ß stimulates cyclooxygenase-2 (COX-2) and prostaglandins production of pulp cells and affects the pulpal inflammation and repair. However, the effects of IL-1ß on Monocyte Chemotactic Factor-1 (MCP-1) of dental pulp cells and its relation to transforming growth factor ß-activated kinase-1 (TAK1), PI3K/Akt, and MEK/ERK signaling and COX activation are not fully clear. DESIGN: Human dental pulp cells were exposed to IL-1ß with/without pretreatment and co-incubation by aspirin (a COX inhibitor), 5z-7-oxozeaenol (a TAK1 inhibitor), LY294002 (a PI3K/Akt inhibitor) or U0126 (a MEK/ERK inhibitor). Viable cell number was evaluated by MTT assay. MCP-1 mRNA expression was tested by reverse transcriptase-polymerase chain reaction (RT-PCR). MCP-1 and COX-2 protein expression was studied by western blot. MCP-1 in the culture medium was measure by ELISA. RESULTS: IL-1ß showed little cytotoxicity to pulp cells. It stimulated MCP-1 mRNA and protein expression and MCP-1 secretion. Aspirin, U0126, LY294002 and 5z-7-oxozeaenol attenuated the IL-1ß-induced MCP-1 expression. In addition, 5z-7-oxozeaenol, LY294002, U0126 and aspirin prevented the IL-1ß-induced MCP-1 secretion of pulp cells. CONCLUSION: These results indicate that IL-1ß may be involved in the pulpal inflammatory and healing processes by inducing MCP-1 expression and secretion. These events are related to differential activation of TAK1, PI3K/Akt and MEK/ERK 1/2 signaling and COX activation. These results are important for future pharmacologic intervention of pulpal inflammatory diseases.

In vitro study of dentin hypersensitivity treated by Nd:YAP laser and bioglass.

OBJECTIVES: An ideal material has yet to be discovered that can completely treat dentin hypersensitivity. However, if a highly biocompatible material such as bioglass, could be melted by laser irradiation to achieve better sealing depth for dentinal tubules, it may subsequently bond to dentin structures under a physiological environment and offer a prolonged therapeutic effect. METHODS: The authors used four types of energy parameters to melt the composition-modified bioglass. These four types were 30 Hz, 330 mJ/pulse (G+ mode), 30 Hz, 160 mJ/pulse (G- mode), 10 Hz, 400 mJ/pulse (D+ mode), and 10 Hz, 200 mJ/pulse (D- mode). The temperature elevation, occlusive depth of bioglass, and phase changes in the bioglass after laser irradiation were evaluated by means of scanning electron microscope (SEM), thermometer, and X-ray diffractometer (XRD). RESULTS: The occlusive depths of 2 and 10 microm in the dentinal tubules were achieved when the bioglass underwent 30 Hz, 160 mJ/pulse (G- mode) and 30 Hz, 330 mJ/pulse (G+ mode) of laser treatments, respectively. The bioglass experienced a temperature increase of less than 600 degrees C, and no phase transformation was observed after Nd:YAP laser irradiation. SIGNIFICANCE: The melting point of a composition-modified bioglass could be reduced and its use plus Nd:YAP laser have the potential in clinical use to treat dentin hypersensitivity.

Synthesis and structure-activity relationships of 3-aminobenzophenones as antimitotic agents.

A new series of 3-aminobenzophenone compounds as potent inhibitors of tubulin polymerization was discovered based on the mimic of the aminocombretastatin molecular skeleton. Lead compounds 5 and 11, with alkoxy groups at the C-4 position of B-ring, were potent cytotoxic agents and inhibitors of tubulin polymerization through the binding to the colchicine-binding site of tubulin. The corresponding antitubulin activities of 5 and 11 were similar to or greater than combretastatin A-4 and AVE-8063. Replacement of the methoxy group with a chloro group in the B ring of aminobenzopheneones (3, 8, and 9) caused drastic decrease in cytotoxic and antitubulin activity except in compounds 4 and 10, which could result from a unique alignment between chloro and amino groups located at the para position to each other. SAR information revealed that introduction of an amino group at the C-3 position in B ring of benzophenones, in addition to a methoxy group at the C-4 position, plays an important role for maximal cytotoxicity.

Synthesis and structure-activity relationship of 2-aminobenzophenone derivatives as antimitotic agents.

A new type of inhibitor of tubulin polymerization was discovered on the basis of the combretastatin molecular skeleton. The lead compounds in this series, compounds 6 and 7, strongly inhibited tubulin polymerization in vitro and significantly arrested cells at the G(2)/M phase. Compounds 6 and 7 yielded 50- to 100-fold lower IC(50) values than did combretastatin A-4 against Colo 205, NUGC3, and HA22T human cancer cell lines as well as similar or greater growth inhibitory activities than did combretastain A-4 against DLD-1, HR, MCF-7, DU145, HONE-1, and MES-SA/DX5 human cancer cell lines. Structure-activity relationship information revealed that introduction of an amino group at the ortho position of the benzophenone ring plays an integral role for increased growth inhibition.

Concise synthesis and structure-activity relationships of combretastatin A-4 analogues, 1-aroylindoles and 3-aroylindoles, as novel classes of potent antitubulin agents.

The synthesis and study of the structure-activity relationships of two new classes of synthetic antitubulin compounds based on 1-aroylindole and 3-aroylindole skeletons are described. Lead compounds 3, 10, and 14 displayed potent cytotoxicities with IC50 = 0.9-26 nM against human NUGC3 stomach, MKN45 stomach, MESSA uterine, A549 lung, and MCF-7 breast carcinoma cell lines. The inhibition of proliferation correlated with in vitro polymerization inhibitory activities. Structure-activity relationships revealed that 6-methoxy substitution of 3-aroylindoles and 5-methoxy substitution of 1-aroylindoles contribute to a significant extent for maximal activity by mimicking the para substitution of the methoxy group to the carbonyl group in the case of aminobenzophenones. Addition of a methyl group at the C-2 position on the indole ring exerts an increased potency. The 3,4,5-trimethoxybenzoyl moiety was necessary for better activity but not essential and can be replaced by 3,5-dimethoxybenzoyl and 3,4,5-trimethoxybenzyl moieties. We conclude that 1- and 3-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment.