Browsing by Author "Aguayo, Sebastian "

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    Antibacterial Effect of Honey-Derived Exosomes Containing Antimicrobial Peptides Against Oral Streptococci
    (2021) Leiva-Sabadini, Camila ; Alvarez, Simon ; Barrera, Nelson P.; Schuh, Christina M.A.P. ; Aguayo, Sebastian
    Purpose: Recently, our group found exosome-like extracellular vesicles (EVs) in Apis mellifera honey displaying strong antibacterial effects; however, the underlying mechanism is still not understood. Thus, the aim of this investigation was to characterize the molecular and nanomechanical properties of A. mellifera honey-derived EVs in order to elucidate the mechanisms behind their antibacterial effect, as well as to determine differential antibiofilm properties against relevant oral streptococci.
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    Bacterial adhesion to collagens: implications for biofilm formation and disease progression in the oral cavity
    (2021) Aguayo, Sebastian
    Collagen is the most abundant structural protein in the body and the main component of the extracellular matrix of most tissues, including dentine and periodontal tissues. Despite the well-characterized role of collagen and specifically type-I collagen, as a ligand for host cells, its role as a substrate for bacterial adhesion and biofilm formation is less explored. Therefore, the purpose of this review is to discuss recent findings regarding the adhesion of oral bacteria to collagen surfaces and its role in the progression and severity of oral and systemic diseases. Initial oral colonizers such as streptococci have evolved collagen-binding proteins (cbp) that are important for the colonization of dentine and periodontal tissues. Also, periodontal pathogens such as Porphyromonas gingivalis and Tannerella forsythia utilise cbps for tissue sensing and subsequent invasion. The implications of bacteria-collagen coupling in the context of collagen biomaterials and regenerative dentistry approaches are also addressed. Furthermore, the importance of interdisciplinary techniques such as atomic force microscopy for the nanocharacterization of bacteria-collagen interactions is also considered. Overall, understanding the process of oral bacterial adhesion onto collagen is important for developing future therapeutic approaches against oral and systemic diseases, by modulating the early stages of biofilm formation.
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    Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration
    (2020) Aguayo, Sebastian
    Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Creutzfeldt-Jakob disease (CJD) are brain conditions affecting millions of people worldwide. These diseases are associated with the presence of amyloid-beta (A beta), alpha synuclein (alpha-Syn) and prion protein (PrP) depositions in the brain, respectively, which lead to synaptic disconnection and subsequent progressive neuronal death. Although considerable progress has been made in elucidating the pathogenesis of these diseases, the specific mechanisms of their origins remain largely unknown. A body of research suggests a potential association between host microbiota, neuroinflammation and dementia, either directly due to bacterial brain invasion because of barrier leakage and production of toxins and inflammation, or indirectly by modulating the immune response. In the present review, we focus on the emerging topics of neuroinflammation and the association between components of the human microbiota and the deposition of A beta, alpha-Syn and PrP in the brain. Special focus is given to gut and oral bacteria and biofilms and to the potential mechanisms associating microbiome dysbiosis and toxin production with neurodegeneration. The roles of neuroinflammation, protein misfolding and cellular mediators in membrane damage and increased permeability are also discussed.
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    Dependency of hydration and growth conditions on the mechanical properties of oral biofilms
    (2021) Aguayo, Sebastian
    Within the oral cavity, dental biofilms experience dynamic environments, in part due to changes in dietary content, frequency of intake and health conditions. This can impact bacterial diversity and morpho-mechanical properties. While phenotypic properties of oral biofilms are closely related to their composition, these can readily change according to dynamic variations in the growth environment and nutrient availability. Understanding the interlink between phenotypic properties, variable growth conditions, and community characterization is an essential requirement to develop structure-property relationships in oral-biofilms. In this study, the impact of two distinct growth media types with increasing richness on the properties of oral biofilms was assessed through a new combination of in-vitro time-lapse biophysical methods with microbiological assays. Oral biofilms grown in the enriched media composition presented a decrease in their pH, an increase in soluble EPS production, and a severe reduction in bacterial diversity. Additionally, enriched media conditions presented an increase in biofilm volumetric changes (upon hydration) as well as a reduction in elastic modulus upon indentation. With hydration time considered a major factor contributing to changes in biofilm mechanical properties, we have shown that it is less associated than media richness. Future investigations can now use this time-lapse approach, with a clearer focus on the extracellular matrix of oral biofilms dictating their morpho-mechanical properties.
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    Extracellular vesicle production by oral bacteria related to dental caries and periodontal disease: role in microbe-host and interspecies interactions
    (Taylor and Francis Ltd., 2024) Leiva Sabadini, Camila; Saavedra, Paula; Inostroza, Carla; Aguayo, Sebastian
    © 2024 Informa UK Limited, trading as Taylor & Francis Group.Extracellular vesicles (EVs) are cell membrane-derived structures between 20-400 nm in size. In bacteria, EVs play a crucial role in molecule secretion, cell wall biogenesis, cell-cell communication, biofilm development, and host-pathogen interactions. Despite these increasing reports of bacterial-derived vesicles, there remains a limited number of studies that summarize oral bacterial EVs, their cargo, and their main biological functions. Therefore, the aim of this review is to present the latest research on oral bacteria-derived EVs and how they can modulate various physiological and pathological processes in the oral cavity, including the pathogenesis of highly relevant diseases such as dental caries and periodontitis and their systemic complications. Overall, caries-associated bacteria (such as Streptococcus mutans) as well as periodontal pathogens (including the red complex pathogens Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) have all been shown to produce EVs that carry an array of virulent factors and molecules involved in biofilm and immune modulation, bacterial adhesion, and extracellular matrix degradation. As bacterial EV production is strongly impacted by genotypic and environmental variations, the inhibition of EV genesis and secretion remains a key potential future approach against oral diseases.
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    Aloe vera peel-derived nanovesicles display anti-inflammatory properties and prevent myofibroblast differentiation
    (2024) Ramirez, Orlando; Pomareda, Florencia; Olivares, Belen; Huang, Ya-Lin; Zavala, Gabriela; Carrasco-Rojas, Javiera; Alvarez, Simon; Leiva-Sabadini, Camila; Hidalgo, Valeria; Romo, Pablo; Sanchez, Matias; Vargas, Ayleen; Martinez, Jessica; Aguayo, Sebastian; Schuh, Christina M. A. P.
    Background: Aloe vera (AV) is a medicinal plant, most known for its beneficial effects on a variety of skin conditions. Its known active compounds include carbohydrates and flavonoids such as quercetin and kaempferol, among others. In the past decade, plant nanovesicles (NVs) have gained considerable interest as interkingdom communicators, presenting an opportunity for clinical standardization of natural products. In this study, we aimed to assess the potential of AVpNVs for the treatment of burn wounds.
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    Microfabrication-based engineering of biomimetic dentin-like constructs to simulate dental aging
    (2024) Alvarez, Simon; Morales, Jose; Tiozzo-Lyon, Paola; Berrios, Pablo; Barraza, Valentina; Simpson, Kevin; Ravasio, Andrea; Monforte Vila, Xavier; Teuschl-Woller, Andreas; Schuh, Christina M. A. P.; Aguayo, Sebastian
    Human dentin is a highly organized dental tissue displaying a complex microarchitecture consisting of micrometer-sized tubules encased in a mineralized type-I collagen matrix. As such, it serves as an important substrate for the adhesion of microbial colonizers and oral biofilm formation in the context of dental caries disease, including root caries in the elderly. Despite this issue, there remains a current lack of effective biomimetic in vitro dentin models that facilitate the study of oral microbial adhesion by considering the surface architecture at the micro- and nanoscales. Therefore, the aim of this study was to develop a novel in vitro microfabricated biomimetic dentin surface that simulates the complex surface microarchitecture of exposed dentin. For this, a combination of soft lithography microfabrication and biomaterial science approaches were employed to construct a micropitted PDMS substrate functionalized with mineralized type-I collagen. These dentin analogs were subsequently glycated with methylglyoxal (MGO) to simulate dentin matrix aging in vitro and analyzed utilizing an interdisciplinary array of techniques including atomic force microscopy (AFM), elemental analysis, and electron microscopy. AFM force-mapping demonstrated that the nanomechanical properties of the biomimetic constructs were within the expected biological parameters, and that mineralization was mostly predominated by hydroxyapatite deposition. Finally, dual-species biofilms of Streptococcus mutans and Candida albicans were grown and characterized on the biofunctionalized PDMS microchips, demonstrating biofilm-specific morphologic characteristics and confirming the suitability of this model for the study of early biofilm formation under controlled conditions. Overall, we expect that this novel biomimetic dentin model could serve as an in vitro platform to study oral biofilm formation or dentin-biomaterial bonding in the laboratory without the need for animal or human tooth samples in the future., Our study aimed to develop a novel in vitro microfabricated biomimetic dentin surface that simulates the complex surface microarchitecture of exposed dentin, as well as age-derived glycation of teeth, for the growth of polymicrobial oral biofilms.
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    Modulation of the Biophysical and Biochemical Properties of Collagen by Glycation for Tissue Engineering Applications
    (2022) Vaez, Mina ; Asgari, Meisam ; Hirvonen, Liisa ; Bakir, Gorkem ; Aguayo, Sebastian ; Schuh, Christina M. ; Gough, Kathleen ; Bozec, Laurent
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    Modulation of the biophysical and biochemical properties of collagen by glycation for tissue engineering applications
    (2023) Vaez, Mina; Asgari, Meisam; Hirvonen, Liisa; Bakir, Gorkem; Khattignavong, Emilie; Ezzo, Maya; Aguayo, Sebastian; Schuh, Christina M.; Gough, Kathleen; Bozec, Laurent
    The structural and functional properties of collagen are modulated by the presence of intramolecular and intermolecular crosslinks. Advanced Glycation End-products (AGEs) can produce intermolecular crosslinks by bonding the free amino groups of neighbouring proteins. In this research, the following hypothesis is explored: The accumulation of AGEs in collagen decreases its proteolytic degradation rates while increas-ing its stiffness. Fluorescence Lifetime Imaging (FLIM) and Fourier-transform infrared spectroscopy (FTIR) detect biochemical changes in collagen scaffolds during the glycation process. The accumulation of AGEs increases exponentially in the collagen scaffolds as a function of Methylglyoxal (MGO) concentration by performing autofluorescence measurement and competitive ELISA. Glycated scaffolds absorb water at a much higher rate confirming the direct affinity between AGEs and interstitial water within collagen fib-rils. In addition, the topology of collagen fibrils as observed by Atomic Force Microscopy (AFM) is a lot more defined following glycation. The elastic modulus of collagen fibrils decreases as a function of gly-cation, whereas the elastic modulus of collagen scaffolds increases. Finally, the enzymatic degradation of collagen by bacterial collagenase shows a sigmoidal pattern with a much slower degradation rate in the glycated scaffolds. This study identifies unique variations in the properties of collagen following the accumulation of AGEs.Statement of significanceIn humans, Advanced Glycation End-products (AGEs) are naturally produced as a result of aging process. There is an evident lack of knowledge in the basic science literature explaining the biomechanical impact of AGE-mediated crosslinks on the functional and structural properties of collagen at both the nanoscale (single fibrils) and mesoscale (bundles of fibrils). This research, demonstrates how it is possible to harness this natural phenomenon in vitro to enhance the properties of engineered collagen fibrils and scaffolds. This study identifies unique variations in the properties of collagen at nanoscale and mesoscale following accumulation of AGEs. In their approach, they investigate the unique properties conferred to collagen, namely enhanced water sorption, differential elastic modulus, and finally sigmoidal proteolytic degrada-tion behavior.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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    Pathogenesis-Guided Engineering: pH-Responsive Imprinted Polymer Co-Delivering Folate for Inflammation-Resolving as Immunotherapy in Implant-Related Infections
    (2024) Costa, Raphael C.; Nagay, Bruna E.; Villa, Javier E. L.; Sotomayor, Maria D. P. T.; Neres, Lariel Chagas da Silva; Benso, Bruna; Aguayo, Sebastian; Sacramento, Catarina M.; Ruiz, Karina G. S.; Spada, Fernanda P.; de Avila, Erica Dorigatti; da Costa, Monique G.; Faverani, Leonardo P.; Cintra, Luciano T. A.; Souza, Joao Gabriel S.; Barao, Valentim A. R.
    Folate (FT) is a suitable targeting ligand for folate receptors (FOLR) overexpressed on inflamed cells. Thus, FT-loaded polymers can be used as FOLRs-targeted immunotherapy to positively modulate the inflammatory process. A novel biodegradable imprinted polymer with a FT delivery mechanism driven by pH changes [PCL-MIP@FT] is designed with molecularly imprinted technology. The pH mechanism is validated in vitro, demonstrating that an acidic environment accelerated and increased the release of FT for a period of 7 days (similar to 100 mu g mL-1). For the first time, FT receptors (FOLR-1 and FOLR-3) are discovered and also overexpressed on activated human gingival fibroblasts, representing a favorable target in the oral environment. Although FT itself does not have antimicrobial effects, the nanomechanical properties of biofilm are changed after topical FT administration. In vivo systemic toxicity of PCL-MIP@FT has been demonstrated to be a safe biomaterial (up to 1.3 mg kg-1). When the PCL-MIP@FT is assessed in the subcutaneous tissue, it promoted an alleviating inflammation and may be able to stimulate tissue repair. The present findings have demonstrated the reliable in vitro and in vivo anti-inflammatory actions of FT-loaded polymer and support its use as a novel drug-free therapeutic platform for modulating and mitigating inflammatory responses in dental implant-related infections.