Department of Biomedical and Applied Sciences Works

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    3D-Image Analysis of the Impact of Toothpaste Abrasivity on the Progression of Simulated Non-Carious Cervical Lesions
    (Elsevier, 2018) Sabrah, Alaa H.; Turssi, Cecilia P.; Lippert, Frank; Eckert, George J.; Kelly, Adam B.; Hara, Anderson T.; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Objectives To investigate the effect of toothpaste abrasive level on the progression of non-carious cervical lesions (NCCLs) using 3D-image subtraction. Methods Upper first premolars were allocated into seven groups (n = 16) of toothpaste/abrasive slurries: A-Zeodent113/5%, B-Zeodent124/10%, C-Zeodent103/15%, D-Sensodyne Pronamel, E-Crest Cavity-Protection, F-Crest Pro-Health-Whitening, and G-Deionized water (DIW). Teeth were mounted on acrylic blocks, and their root surfaces covered with acrylic resin, except for 2-mm near the cemento-enamel junction that was exposed to toothbrushing. Specimens were brushed with the slurries for 5000-, 15,000-, 35,000- and 65,000-strokes. Impressions were taken at baseline and after each brushing time, and then scanned by a 3D optical profilometer. Dentine volume loss was calculated by image subtraction software and subjected to mixed-model ANOVA and multiple comparison tests (α = 0.05). Results No significant differences among slurries were observed at 5000 and 15,000. At 35,000, F showed higher loss than all other groups except C, which did not differ from the others. At 65,000, F (4.19 ± 3.29 mm3) showed the highest loss, followed by C (2.33 ± 1.47 mm3), which differed from all the other groups except B (1.85 ± 0.91 mm3). Groups B, A (1.35 ± 0.65 mm3), D (1.17 ± 0.48 mm3), E (1.40 ± 0.68 mm3) and G (1.12 ± 0.73 mm3) did not differ from each other. Groups F and C showed significant increase of volume loss starting at 35,000, while B, A, D and E only at 65,000; no increase loss was observed for G. Conclusions 3D-image subtraction was able to quantify and differentiate tooth loss, but only at advanced stages. The progression of NCCLs was more evident and faster for highly abrasive slurries. Clinical significance Upon root dentin exposure, brushing with lower abrasive dentifrices is advisable to reduce the risk for NCCLs development.
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    The ability of dual whitening anti-caries mouthrinses to remove extrinsic staining and enhance caries lesion remineralization – An in vitro study
    (Elsevier, 2020) Al-Shahrani, Ahid A.; Levon, John A.; Hara, Anderson T.; Tang, Qing; Lippert, Frank; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Objectives This laboratory study investigated the ability of dual whitening anti-caries mouthrinses to remove extrinsic staining from artificially stained caries lesions and to enhance their remineralization and fluoridation. Materials and Methods Early caries lesions were created in bovine enamel specimens. The lesions were artificially stained and pH cycled for 10 days with the daily cycling regimen consisting of twice daily 60s-treatments with one of 11 mouthrinses, a 4-h demineralization period and artificial saliva treatments in between. Mouthrinses were eight commercially available products, all containing 100 ppm fluoride but utilizing hydrogen peroxide, pyro-, tri- or hexametaphosphate salts and/or sodium bicarbonate. The three control mouthrinses were 100 ppm fluoride, 30 % hydrogen peroxide and deionized water. Enamel color changes (ΔE) were determined spectrophotometrically. Vickers surface microhardness (VHN) was used to determine lesion remineralization. Enamel fluoride content (EFC) was determined using the microbiopsy technique. Data were analyzed using ANOVA. Results ΔE was significantly different among groups (p = 0.0045). Thirty percent hydrogen peroxide was superior to all other mouthrinses, while there were no differences between commercial mouthrinses and deionized water. There were small, directional but non-significant differences between commercial mouthrinses with those containing hydrogen peroxide providing better whitening. There were no significant differences between mouthrinses in their ability to remineralize caries lesions (p = 0.2898). EFC differed among groups (p < 0.0001), with the two mouthrinses containing pyrophosphate salts having lower EFC than all but the deionized water group. Conclusions Artificially stained caries lesions show reduced susceptibility to fluoride remineralization and whitening effects of commercial whitening and anti-caries mouthrinses. Clinical Relevance Artificially stained caries lesions appear to require stronger than over-the-counter interventions to successfully whiten and remineralizing them.
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    Adipose-derived stem cell conditioned medium for the treatment of amyotrophic lateral sclerosis: pre-clinical evidence and potential for clinical application
    (Medknow Publications, 2019-09) Walker, Chandler L.; Department of Biomedical and Applied Sciences, School of Dentistry
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    Adipose-derived stem cell conditioned medium impacts asymptomatic peripheral neuromuscular denervation in the mutant superoxide dismutase (G93A) transgenic mouse model of amyotrophic lateral sclerosis
    (IOS, 2018-09) Walker, Chandler L.; Meadows, Rena M.; Merfeld-Clauss, Stephanie; Du, Yansheng; March, Keith L.; Jones, Kathryn J.; Biomedical Sciences and Comprehensive Care, School of Dentistry
    Background:Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ∼47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. Objective:To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. Methods:We confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and post-synaptic acetylcholine receptors (AchR) by α-bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200μl ASC-CM or vehicle medium daily from post-natal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with α-bungarotoxin in gastrocnemius muscle. Results:Intact NMJs were significantly decreased in 47 day old mSOD1G93A mice (p < 0.05), and daily systemic ASC-CM prevented disease-induced NMJ denervation compared to vehicle treated mice (p < 0.05). Conclusions:Our results lay the foundation for testing the long-term neurological benefits of systemic ASC-CM therapy in the mSOD1G93A mouse model of ALS.
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    Advanced biomaterials for periodontal tissue regeneration
    (Wiley, 2022) Daghrery, Arwa; Bottino, Marco C.; Biomedical and Applied Sciences, School of Dentistry
    The periodontium is a suitable target for regenerative intervention, since it does not functionally restore itself after disease. Importantly, the limited regeneration capacity of the periodontium could be improved with the development of novel biomaterials and therapeutic strategies. Of note, the regenerative potential of the periodontium depends not only on its tissue‐specific architecture and function, but also on its ability to reconstruct distinct tissues and tissue interfaces, suggesting that the advancement of tissue engineering approaches can ultimately offer new perspectives to promote the organized reconstruction of soft and hard periodontal tissues. Here, we discuss material‐based, biologically active cues, and the application of innovative biofabrication technologies to regenerate the multiple tissues that comprise the periodontium.
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    Advanced Scaffolds for Dental Pulp and Periodontal Regeneration
    (Elsevier, 2017-10) Bottino, Marco C.; Pankajakshan, Divya; Nör, Jacques E.; Biomedical Sciences and Comprehensive Care, School of Dentistry
    No current therapy promotes root canal disinfection and regeneration of the pulp-dentin complex in cases of pulp necrosis. Antibiotic pastes used to eradicate canal infection negatively affect stem cell survival. Three-dimensional easy-to-fit antibiotic-eluting nanofibers, combined with injectable scaffolds, enriched or not with stem cells and/or growth factors, may increase the likelihood of achieving predictable dental pulp regeneration. Periodontitis is an aggressive disease that impairs the integrity of tooth-supporting structures and may lead to tooth loss. The latest advances in membrane biomodification to endow needed functionalities and technologies to engineer patient-specific membranes/constructs to amplify periodontal regeneration are presented.
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    Age-dependent effects of the recombinant spike protein/SARS-CoV-2 on the M–CSF– and IL-34-differentiated macrophages in vitro
    (Elsevier, 2021) Duarte, Carolina; Akkaoui, Juliet; Ho, Anny; Garcia, Christopher; Yamada, Chiaki; Movila, Alexandru; Biomedical and Applied Sciences, School of Dentistry
    The SARS-CoV-2 virus causes elevated production of senescence-associated secretory phenotype (SASP) markers by macrophages. SARS-CoV-2 enters macrophages through its Spike-protein aided by cathepsin (Cat) B and L, which also mediate SASP production. Since M-CSF and IL-34 control macrophage differentiation, we investigated the age-dependent effects of the Spike-protein on SASP-related pro-inflammatory-cytokines and nuclear-senescence-regulatory-factors, and CatB, L and K, in mouse M-CSF- and IL-34-differentiated macrophages. The Spike-protein upregulated SASP expression in young and aged male M-CSF-macrophages. In contrast, only young and aged male IL-34-macrophages demonstrated significantly reduced pro-inflammatory cytokine expression in response to the Spike-protein in vitro. Furthermore, the S-protein elevated CatB expression in young male M-CSF-macrophages and young female IL-34-macrophages, whereas CatL was overexpressed in young male IL-34- and old male M-CSF-macrophages. Surprisingly, the S-protein increased CatK activity in young and aged male M-CSF-macrophages, indicating that CatK may be also involved in the COVID-19 pathology. Altogether, we demonstrated the age- and sex-dependent effects of the Spike-protein on M-CSF and IL-34-macrophages using a novel in vitro mouse model of SARS-CoV-2/COVID-19.
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    Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass
    (Elsevier, 2019) Maupin, Kevin A.; Himes, Evan R.; Plett, Artur P.; Chua, Hui Lin; Singh, Pratibha; Ghosh, Joydeep; Mohamad, Safa F.; Abeysekera, Irushi; Fisher, Alexa; Sampson, Carol; Hong, Jung-Min; Childress, Paul; Alvarez, Marta; Srour, Edward F.; Bruzzaniti, Angela; Pelus, Louis M.; Orschell, Christie M.; Kacena, Melissa A.; Orthopaedic Surgery, School of Medicine
    Osteoblast number and activity decreases with aging, contributing to the age-associated decline of bone mass, but the mechanisms underlying changes in osteoblast activity are not well understood. Here, we show that the age-associated bone loss critically depends on impairment of the ability of megakaryocytes (MKs) to support osteoblast proliferation. Co-culture of osteoblast precursors with young MKs is known to increase osteoblast proliferation and bone formation. However, co-culture of osteoblast precursors with aged MKs resulted in significantly fewer osteoblasts compared to co-culture with young MKs, and this was associated with the downregulation of transforming growth factor beta. In addition, the ability of MKs to increase bone mass was attenuated during aging as transplantation of GATA1low/low hematopoietic donor cells (which have elevated MKs/MK precursors) from young mice resulted in an increase in bone mass of recipient mice compared to transplantation of young wild-type donor cells, whereas transplantation of GATA1low/low donor cells from old mice failed to enhance bone mass in recipient mice compared to transplantation of old wild-type donor cells. These findings suggest that the preservation or restoration of the MK-mediated induction of osteoblast proliferation during aging may hold the potential to prevent age-associated bone loss and resulting fractures.
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    Alternative Direct Restorative Materials for Dental Amalgam: A Concise Review Based on an FDI Policy Statement
    (Elsevier, 2024) Schmalz, Gottfried; Schwendicke, Falk; Hickel, Reinhard; Platt, Jeffrey A.; Biomedical and Applied Sciences, School of Dentistry
    Dental restorative procedures remain a cornerstone of dental practice, and for many decades, dental amalgam was the most frequently employed material. However, its use is declining, mainly driven by its poor aesthetics and by the development of tooth-coloured adhesive materials. Furthermore, the Minamata Convention agreed on a phase-down on the use of dental amalgam. This concise review is based on a FDI Policy Statement which provides guidance on the selection of direct restorative materials as alternatives to amalgam. The Policy Statement was informed by current literature, identified mainly from PubMed and the internet. Ultimately, dental, oral, and patient factors should be considered when choosing the best material for each individual case. Dental factors include the dentition, tooth type, and cavity class and extension; oral aspects comprise caries risk profiles and related risk factors; and patient-related aspects include systemic risks/medical conditions such as allergies towards certain materials as well as compliance. Special protective measures (eg, a no-touch technique, blue light protection) are required when handling resin-based materials, and copious water spray is recommended when adjusting or removing restorative materials. Cost and reimbursement policies may need to be considered when amalgam alternatives are used, and the material recommendation requires the informed consent of the patient. There is no single material which can replace amalgam in all applications; different materials are needed for different situations. The policy statement recommends using a patient-centred rather than purely a material-centred approach. Further research is needed to improve overall material properties, the clinical performance, the impact on the environment, and cost-effectiveness of all alternative materials.
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    Alveolar bone protection by targeting the SH3BP2-SYK axis in osteoclasts
    (Wiley, 2020-02) Kittaka, Mizuho; Yoshimoto, Tetsuya; Schlosser, Collin; Rottapel, Robert; Kajiya, Mikihito; Kurihara, Hidemi; Reichenberger, Ernst J.; Ueki, Yasuyoshi; Biomedical Sciences and Comprehensive Care, School of Dentistry
    Periodontitis is a bacterially induced chronic inflammatory condition of the oral cavity where tooth-supporting tissues including alveolar bone are destructed. Previously, we have shown that the adaptor protein SH3-domain binding protein 2 (SH3BP2) plays a critical role in inflammatory response and osteoclastogenesis of myeloid lineage cells through spleen tyrosine kinase (SYK). In this study, we show that SH3BP2 is a novel regulator for alveolar bone resorption in periodontitis. Micro-CT analysis of SH3BP2-deficient (Sh3bp2 -/- ) mice challenged with ligature-induced periodontitis revealed that Sh3bp2 -/- mice develop decreased alveolar bone loss (male 14.9% ± 10.2%; female 19.0% ± 6.0%) compared with wild-type control mice (male 25.3% ± 5.8%; female 30.8% ± 5.8%). Lack of SH3BP2 did not change the inflammatory cytokine expression and osteoclast induction. Conditional knockout of SH3BP2 and SYK in myeloid lineage cells with LysM-Cre mice recapitulated the reduced bone loss without affecting both inflammatory cytokine expression and osteoclast induction, suggesting that the SH3BP2-SYK axis plays a key role in regulating alveolar bone loss by mechanisms that regulate the bone-resorbing function of osteoclasts rather than differentiation. Administration of a new SYK inhibitor GS-9973 before or after periodontitis induction reduced bone resorption without affecting inflammatory reaction in gingival tissues. In vitro, GS-9973 treatment of bone marrow-derived M-CSF-dependent macrophages suppressed tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation with decreased mineral resorption capacity even when GS-9973 was added after RANKL stimulation. Thus, the data suggest that SH3BP2-SYK is a novel signaling axis for regulating alveolar bone loss in periodontitis and that SYK can be a potential therapeutic target to suppress alveolar bone resorption in periodontal diseases.