Recent advances in injectable hydrogel therapies for periodontitis.

Periodontitis is an immune-inflammatory disease caused by dental plaque, and deteriorates the periodontal ligament, causes alveolar bone loss, and may lead to tooth loss. To treat periodontitis, antibacterial and anti-inflammation approaches are required to reduce bone loss. Thus, appropriate drug administration methods are significant. Due to their "syringeability", biocompatibility, and convenience, injectable hydrogels and associated methods have been extensively studied and used for periodontitis therapy. Such hydrogels are made from natural and synthetic polymer materials using physical and/or chemical cross-linking approaches. Interestingly, some injectable hydrogels are stimuli-responsive hydrogels, which respond to the local microenvironment and form hydrogels that release drugs. Therefore, as injectable hydrogels are different and highly varied, we systematically reviewed the periodontal treatment field from three perspectives: raw material sources, cross-linking methods, and stimuli-responsive methods. We then discussed current challenges and opportunities for the translation of hydrogels to clinic, which may guide further injectable hydrogel designs for periodontitis.

Upconversion Nanoplatform Enables Multimodal Imaging and Combinatorial Immunotherapy for Synergistic Tumor Treatment and Monitoring.

Designing a novel nanoplatform that integrates multimodal imaging and synergistic therapy for precision tumor nanomedicines is challenging. Herein, we prepared rare-earth ion-doped upconversion hydroxyapatite (FYH) nanoparticles as nanocarriers coated and loaded respectively with polydopamine (PDA) and doxorubicin (DOX), i.e., FYH-PDA-DOX, for tumor theranostics. The developed FYH-PDA-DOX complexes exhibited desirable photothermal conversion, pH/near-infrared-irradiation-responsive DOX release, and multimodal upconversion luminescence/computed tomography/magnetic resonance imaging performance and helped monitor the metabolic distribution process of the complexes and provided feedback to the therapeutic effect. Upon 808 nm laser irradiation, the fast release of DOX facilitated the photothermal-chemotherapy effect, immunogenic cell death, and antitumor immune response. On combining with the anti-programmed cell death 1 ligand 1 antibody, an enhanced tri-mode photothermal-chemo-immunotherapy synergistic treatment against tumors can be realized. Thus, this treatment elicited potent antitumor immunity, producing appreciable T-cell cytotoxicity against tumors, amplifying tumor suppression, and extending the survival of mice. Therefore, the FYH-PDA-DOX complexes are promising as a smart nanoplatform for imaging-guided synergistic cancer treatment.

Recent progress of rare earth doped hydroxyapatite nanoparticles: Luminescence properties, synthesis and biomedical applications.

Hydroxyapatite nanoparticles (HAP NPs) are host materials and can be modified with various substrates and dopants. Among them, rare earth (RE) ions doped HAP NPs have gathered attention due to their unique physicochemical and imaging properties. Compared to other fluorescence probes, RE-doped HAP NPs display advantages in high brightness, high contrast, photostability, nonblinking, and narrow emission bands. Meanwhile, their intrinsic features (composition, morphology, size, crystallinity, and luminescence intensity) can be adjusted by changing the dopant ratio, synthesizing temperature, reaction time, and techniques. And they have been used in various biomedical applications, including imaging probe, drug delivery, bone tissue engineering, and antibacterial studies. This review surveys the luminescent properties, fluorescence enhancement, synthetic methods, and biocompatibility of various RE-doped HAP NPs consolidated from different research works, for their employments in biomedical applications. For this literature review, an electronic search was conducted in the Pubmed, Web of Science, Google Scholar, Scopus and SciFinder databases, using the keywords: hydroxyapatite, rare earth, lanthanide, fluorescence, and imaging. Literature searches of English-language publications from 1979 with updates through April, 2022, and a total of 472 potential papers were identified. In addition, a few references were located by noting their citation in other studies reviewed. STATEMENT OF SIGNIFICANCE: Hydroxyapatite nanoparticles (HAP NPs) have a broad range of promising biological applications. Although prospective biomedical applications are not limited to rare earth-doped hydroxyapatite nanoparticles (RE-doped HAP NPs), some cases do make use of the distinctive features of RE-elements to achieve the expected functions for HAP families. This review surveys the luminescent properties, synthetic methods, and biocompatibility of various RE-doped HAP NPs consolidated from different research works, for their employments in biomedical applications, including imaging probe, drug delivery, bone tissue repair and tracking, and anti-bacteria. Overall, we expect to shed some light on broadening the research and application of RE-doped HAP NPs in biomedical field.

A novel theranostic nanoplatform for imaging-guided chemo-photothermal therapy in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is highly malignant and invasive, and current treatments are limited due to serious side effects and unsatisfactory outcomes. Here, we reported the terbium ion-doped hydroxyapatite (HATb) nanoparticle as a luminescent probe to encapsulate both the near-infrared (NIR) photothermal agent polydopamine (PDA) and anticancer doxorubicin (DOX) for imaging-guided chemo-photothermal therapy. The morphology, crystal structure, fluorescence, and composition of HATb-PDA-DOX were characterized. HATb-PDA showed a high DOX loading capacity. A theranostic nanoplatform showed pH/NIR responsive release properties and better antitumor outcomes in OSCC cells than monomodal chemotherapy or photothermal therapy, while keeping side effects at a minimum. Also, the luminescence signal was confirmed to be tracked and the increase of the red/green (R/G) ratio caused by the DOX release could be used to monitor the DOX release content. Furthermore, HATb-PDA-DOX plus NIR treatment synergistically promoted in vitro cell death through the overproduction of reactive oxygen species (ROS), cell cycle arrest, and increased cell apoptosis. Overall, this work presents an innovative strategy in designing a multifunctional nano-system for imaging-guided cancer treatment.

N-acetyl cysteine inhibits lipopolysaccharide-mediated synthesis of interleukin-1ß and tumor necrosis factor-α in human periodontal ligament fibroblast cells through nuclear factor-kappa B signaling.

BACKGROUND: The aim of this study was to investigate the role of n-acetyl cysteine (NAC) in the lipopolysaccharide (LPS)-mediated induction of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) synthesis by human periodontal ligament fibroblast cells (hPDLFs). In addition, we aimed to determine the involvement of the nuclear factor-kappa B (NF-κB) pathway in any changes in IL-1ß and TNF-α expression observed in response to LPS and NAC. METHODS: HPDLFs were obtained by primary culture. The culture medium used in this experiment was Dulbecco's Modified Eagle Medium (DMEM low-glucose). Cells were stimulated with various concentrations of NAC or LPS. Cell proliferation was measured at various time-points with the cell Counting Kit 8 (CCK-8) assay. mRNA levels of IL-1ß and TNF-α were determined by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Protein levels of IL-1ß and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expression levels of NF-κB were measured by western blot and RT-qPCR. RESULTS: The results showed that LPS treatment in hPDLFs induced mRNA and protein expression of IL-1ß, TNF-α, and NF-κB. However, these effects were eliminated by pretreatment with NAC. Pretreatment with both NAC (1 mmol/L) and BAY11-7082 (10 µmol/L) significantly inhibited the NF-κB activity induced by LPS. CONCLUSION: NAC inhibits the LPS-mediated synthesis of tumor TNF-α and IL-1ß in hPDLFs, through the NF-κB pathway.

Effect of phosphoric acid concentration used for etching on the microtensile bond strength to fluorotic teeth.

To evaluate the effects of different etching concentrations of phosphoric acid on the microtensile bond strength of Adper Single Bond 2 to fluorotic teeth.Deidentified extracted teeth were collected, including 30 sound teeth, 30 teeth with mild fluorosis, 30 teeth with moderate fluorosis, and 30 teeth with severe fluorosis. The teeth in each group were randomly divided into 3 subgroups (n = 10) that were subjected to acid etching using 35%, 40%, or 45% phosphoric acid. Adper Single Bond 2 (3M, Saint Paul, MN) was used as the adhesive for bonding Z250 universal resin (3M) to the etched dental enamel. Microtensile testing was used to determine the bond strength. After the microtensile test, the fractured specimens were examined under scanning electron microscopy (SEM).Both dental fluorosis and concentrations of phosphoric acid significantly affected the microshear bond strength of Adper Single Bond 2 to dental enamel. The maximum bond strength was achieved by using 40% phosphoric acid. Failure analysis showed that most failures occurred at the bonding interface. The rates of failures at the bonding interface decreased as the degree of fluorosis increased and as the concentration of phosphoric acid increased from 35% to 45%.The bond strength of fluorosis tooth was lower than that of healthy tooth, the bond strength increased with the increasing concentration of phosphoric acid, but an excessively high acid concentration can conversely lead to an apparent decline in bond strength.

Effect of a filled adhesive as the desensitizer on bond strength of "Self-Adhesive Cements To" differently severity of fluorosed dentin.

The objectives were to evaluate the efficacy of a filled adhesive named Prime & Bond NT (P&B NT) as the dentin desensitizer in occluding fluorosis dentinal tubules and compare the shear bond strength (SBS) of RelyX U200 self-adhesive resin cement (RXU) and RelyX Luting self-adhesive resin-modified glass ionomer cement (RMGIC) before and after P&B NT pretreatment. 176 non-carious fluorosis were classified into four subgroups by the Thylstrup and Fejerskov index (TFI): normal group (TFI = 0), mild group (TFI = 1-3), moderate group (TFI = 4-5), severe group (TFI = 6-9). 160 composite cylinders (4 × 5 mm) were fabricated, then every severity of fluorosed dentin was subjected to four treatments: P&B NT + RXU (n = 40), RXU (n = 40), P&B NT + RMGIC (n = 40), RMGIC (n = 40). The specimens were immersed in water at 37°C for 24 hr first and half of them underwent 5,000 thermocycling before shear bond strength test. A factorial design (factorial 4 × 2 × 2 × 2) was developed to make statistical analysis. Scanning electron microscope (SEM) analysis (n = 16) in cross section and longitudinal section view characterized the occlusion situation of dentinal tubules. P&B NT might occlude dentinal tubules as the dentin desensitizer for normal teeth and mild-moderate fluorosis. P&B NT significantly increased the SBS of RXU (p < .05) but had no statistical significance on the SBS of RMGIC (p > .05). RXU could benefit from P&B NT desensitization to achieve a better quality of adhesion.