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Browsing by Author "Biomedical and Applied Sciences, School of Dentistry"

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    A randomized controlled trial assessing denture adhesive efficacy on denture retention across 13 hours
    (Wiley, 2024-04) Klukowska, Malgorzata; Grender, Julie; Gossweiler, Ana; Biomedical and Applied Sciences, School of Dentistry
    Purpose To compare the effects of two denture adhesive formulations on the bite force required to dislodge a maxillary denture in adult participants during a 13-h test period. Materials and Methods Twenty-two participants with a fair-to-poor fitting maxillary denture opposed by natural dentition or a stable mandibular denture were enrolled in this single-center, randomized, double-blind, two-treatment, 4-period crossover study. Participants were randomly assigned a product usage sequence so that each participant used each product twice during the 4-day test period. The test product was a denture cream adhesive formulated with an optimized calcium/zinc partial salt of polyvinyl methyl ether/maleic acid (Fixodent Ultra technology); the control product was a cream adhesive formulated with a calcium/zinc partial salt of polyvinyl methyl ether/maleic acid (Fixodent Original technology). On each study day, bite force at dislodgement was measured with a gnathodynamometer at baseline, representing the “no adhesive” score. Then, after standardized product application to the participant's existing maxillary denture by site staff, bite force measurements were retaken at 1, 3, 5, 7, 9, 11, and 13 h. The change from baseline and the 13-h area under the bite-force–change-from-baseline curve were analyzed via an analysis of variance. Results Twenty-one participants completed all test periods; one additional participant completed three test periods so 22 participants were included in the analysis. There were 15 females and 7 males with a mean age of 70 years. The mean 13-h area under the bite-force–change-from-baseline curve was 8% greater (p = 0.010) for the test adhesive (114.3 lb) than for the control adhesive (105.9 lb). Both adhesives showed a statistically significant increase in bite force (p < 0.001) at each time point compared to no adhesive. Conclusions The optimized calcium/zinc partial salt of polyvinyl methyl ether/maleic acid test adhesive provided superior maxillary denture retention relative to that of the control adhesive across 13 h. Both adhesives increased bite force at dislodgement compared to no adhesive.
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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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    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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    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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    Analyses of the Effects of Arginine, Nicotine, Serotype and Collagen-Binding Proteins on Biofilm Development by 33 Strains of Streptococcus mutans
    (Frontiers Media, 2021-11-25) Wagenknecht, Dawn R.; Gregory, Richard L.; Biomedical and Applied Sciences, School of Dentistry
    Streptococcus mutans serotype k strains comprise <3% of oral isolates of S. mutans but are prominent in diseased cardiovascular (CV) tissue. Collagen binding protein (CBP) genes, cbm and cnm, are prevalent in serotype k strains and are associated with endothelial cell invasion. Nicotine increases biofilm formation by serotype c strains of S. mutans, but its effects on serotype k strains and strains with CBP are unknown. Saliva contains arginine which alters certain properties of the extracellular polysaccharides (EPS) in S. mutans biofilm. We examined whether nicotine and arginine affect sucrose-induced biofilm of S. mutans serotypes k (n = 23) and c (n = 10) strains with and without CBP genes. Biofilm mass, metabolism, bacterial proliferation, and EPS production were assessed. Nicotine increased biomass and metabolic activity (p < 0.0001); arginine alone had no effect. The presence of a CBP gene (either cbm or cnm) had a significant effect on biofilm production, but serotype did not. Nicotine increased bacterial proliferation and the effect was greater in CBP + strains compared to strains lacking CBP genes. Addition of arginine with nicotine decreased both bacterial mass and EPS compared to biofilm grown in nicotine alone. EPS production was greater in cnm + than cbm + strains (p < 0.0001). Given the findings of S. mutans in diseased CV tissue, a nicotine induced increase in biofilm production by CBP + strains may be a key link between tobacco use and CV diseases.
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    Ascorbic acid as a modulator of inflammatory response against Candida albicans
    (Taylor & Francis, 2024) Moreira Milhan, Noala Vicensoto; da Graça Sampaio, Aline; Koga-Ito, Cristiane Yumi; Bruzzaniti, Angela; Biomedical and Applied Sciences, School of Dentistry
    Aim: To evaluate the behavior of oral keratinocytes in the presence of Vitamin C (Vit C) and its anti-inflammatory potential. Materials & methods: Oral keratinocytes were initially exposed to 0.1-2.5 mM of Vit C and the metabolic activity and cell migration were evaluated using MTS assay and Ibidi culture inserts, respectively. After, the cells were challenged with Candida albicans and inflammatory markers were analyzed by qPCR. Results: The treatment was not cytotoxic, and the highest concentrations increased the metabolic activity at 24 h. Vit C delayed the cell migration at 48 and 72 h. Interestingly, it downregulated the genes IL-8 and IL-1β. Conclusion: Vit C could be an interesting adjuvant to anti-fungal treatment due to its anti-inflammatory potential.
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    Biomimetic and enzyme-responsive dynamic hydrogels for studying cell-matrix interactions in pancreatic ductal adenocarcinoma
    (Elsevier, 2018-04) Liu, Hung-Yi; Korc, Murray; Lin, Chien-Chi; Biomedical and Applied Sciences, School of Dentistry
    The tumor microenvironment (TME) governs all aspects of cancer progression and in vitro 3D cell culture platforms are increasingly developed to emulate the interactions between components of the stromal tissues and cancer cells. However, conventional cell culture platforms are inadequate in recapitulating the TME, which has complex compositions and dynamically changing matrix mechanics. In this study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system through integrating modular thiol-norbornene photopolymerization and enzyme-triggered on-demand matrix stiffening. In particular, gelatin was dually modified with norbornene and 4-hydroxyphenylacetic acid to render this bioactive protein photo-crosslinkable (through thiol-norbornene gelation) and responsive to tyrosinase-triggered on-demand stiffening (through HPA dimerization). In addition to the modified gelatin that provides basic cell adhesive motifs and protease cleavable sequences, hyaluronic acid (HA), an essential tumor matrix, was modularly and covalently incorporated into the cell-laden gel network. We systematically characterized macromer modification, gel crosslinking, as well as enzyme-triggered stiffening and degradation. We also evaluated the influence of matrix composition and dynamic stiffening on pancreatic ductal adenocarcinoma (PDAC) cell fate in 3D. We found that either HA-containing matrix or a dynamically stiffened microenvironment inhibited PDAC cell growth. Interestingly, these two factors synergistically induced cell phenotypic changes that resembled cell migration and/or invasion in 3D. Additional mRNA expression array analyses revealed changes unique to the presence of HA, to a stiffened microenvironment, or to the combination of both. Finally, we presented immunostaining and mRNA expression data to demonstrate that these irregular PDAC cell phenotypes were a result of matrix-induced epithelial-mesenchymal transition (EMT).
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    Carboxyl-terminal modulator protein (CTMP) deficiency mitigates denervation-induced skeletal muscle atrophy
    (Elsevier, 2023-02) Wang, Junmei; Tierney, Lydia; Wilson, Christopher; Phillips, Victoria; Goldman, Lillian; Mumaw, Christen; Muang, En; Walker, Chandler L.; Biomedical and Applied Sciences, School of Dentistry
    Denervated skeletal muscles show decreased Akt activity and phosphorylation, resulting in atrophy. Akt inhibits downstream transcription of atrophy-associated ubiquitin ligases like muscle ring-finger protein 1 (MuRF-1). In addition, reduced Akt signaling contributes to aberrant protein synthesis in muscles. In ALS mice, we recently found that carboxyl-terminator modulator protein (CTMP) expression is increased and correlated with reduced Akt signaling in atrophic skeletal muscle. CTMP has also been implicated in promoting muscle degeneration and catabolism in an in vitro muscle atrophy model. The present study examined whether sciatic nerve injury (SNI) stimulated CTMP expression in denervated skeletal muscle during muscle atrophy. We hypothesized that CTMP deficiency would reduce neurogenic atrophy and reverse Akt signaling downregulation. Compared to the unaffected contralateral muscle, wild-type (WT) gastrocnemius muscle had a significant increase in CTMP (p < 0.05). Furthermore, denervated CTMP knockout (CTMP-KO) gastrocnemius weighed more than WT muscle (p < 0.05). Denervated CTMP-KO gastrocnemius also showed higher Akt and downstream glycogen synthase kinase 3β (GSK3β) phosphorylation compared to WT muscle (p < 0.05) as well as ribosomal proteins S6 and 4E-BP1 phosphorylation (p < 0.001 and p < 0.05, respectively). Moreover, CTMP-KO mice showed significantly lower levels of E3 ubiquitin ligase MuRF-1 and myostatin than WT muscle (p < 0.05). Our findings suggest that CTMP is essential to muscle atrophy after denervation and it may act by reducing Akt signaling, protein synthesis, and increasing myocellular catabolism.
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    Characterizing Curing Efficiency of EGCG-Encapsulated Halloysite Nanotube Modified Adhesives for Durable Dentin–Resin Interfaces
    (MDPI, 2024-12-24) Alhijji, Saleh; Platt, Jeffrey A.; Al-Maflehi, Nassr; Alhotan, Abdulaziz; Haider, Julfikar; Bottino, Marco C.; Windsor, L. Jack; Biomedical and Applied Sciences, School of Dentistry
    Matrix metalloproteinase (MMP)-induced collagen degradation at the resin-dentin interface remains a significant challenge for maintaining the longevity of dental restorations. This study investigated the effects of epigallocatechin-3-gallate (EGCG), a potent MMP inhibitor, on dental adhesive curing efficiency when encapsulated in halloysite nanotubes (HNTs). EGCG-loaded HNTs were incorporated into a commercial dental adhesive (Adper Scotchbond Multi-Purpose) at 7.5% and 15% w/v concentrations. To isolate the effects of each component, the study included three control groups: unmodified adhesive (negative control), adhesive containing only HNTs, and adhesive containing only EGCG (0.16% and 0.32%, equivalent to the EGCG content in EGCG-HNT groups). Degree of conversion (DC), polymerization conversion (PC), and Vickers micro-hardness (VHN) were assessed to evaluate curing efficiency. The addition of 7.5% EGCG-encapsulated HNTs maintained curing properties similar to the control, showing no significant differences in DC (80.97% vs. 81.15%), PC (86.59% vs. 85.81%), and VHN (23.55 vs. 24.12) (p > 0.05). In contrast, direct incorporation of EGCG at 0.32% significantly decreased DC (73.59%), PC (80.63%), and VHN (20.56) values compared to both control and EGCG-HNT groups (p < 0.05). Notably, HNT encapsulation mitigated these negative effects on polymerization, even at higher EGCG concentrations. These findings demonstrate that EGCG encapsulation in HNTs can maintain the curing efficiency of dental adhesives while potentially preserving the MMP-inhibitory benefits of EGCG.
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    Clinical and Radiological Deterioration in a Case of Creutzfeldt–Jakob Disease following SARS-CoV-2 Infection: Hints to Accelerated Age-Dependent Neurodegeneration
    (MDPI, 2021-11-19) Ciolac, Dumitru; Racila, Renata; Duarte, Carolina; Vasilieva, Maria; Manea, Diana; Gorincioi, Nadejda; Condrea, Alexandra; Crivorucica, Igor; Zota, Eremei; Efremova, Daniela; Crivorucica, Veaceslav; Ciocanu, Mihail; Movila, Alexandru; Groppa, Stanislav A.; Biomedical and Applied Sciences, School of Dentistry
    Systemic inflammation and the host immune responses associated with certain viral infections may accelerate the rate of neurodegeneration in patients with Creutzfeldt-Jakob disease (CJD), a rare, transmissible neurodegenerative disease. However, the effects of the newly emerged SARS-CoV-2 infection on the pathogenesis of CJD are unknown. In this study, we describe the case of an elderly female patient with sporadic CJD that exhibited clinical deterioration with the emergence of seizures and radiological neurodegenerative progression following an infection with SARS-CoV-2 and severe COVID-19. Despite efforts to control the progression of the disease, a dismal outcome ensued. This report further evidences the age-dependent neurological effects of SARS-CoV-2 infection and proposes a vulnerability to CJD and increased CJD progression following COVID-19.
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