RESUMO
Fungal pathogens have been designated by the World Health Organization as microbial threats of the highest priority for global health. It remains a major challenge to improve antifungal efficacy at the site of infection while avoiding off-target effects, fungal spreading, and drug tolerance. Here, a nanozyme-based microrobotic platform is developed that directs localized catalysis to the infection site with microscale precision to achieve targeted and rapid fungal killing. Using electromagnetic field frequency modulation and fine-scale spatiotemporal control, structured iron oxide nanozyme assemblies are formed that display tunable dynamic shape transformation and catalysis activation. The catalytic activity varies depending on the motion, velocity, and shape providing controllable reactive oxygen species (ROS) generation. Unexpectedly, nanozyme assemblies bind avidly to fungal (Candida albicans) surfaces to enable concentrated accumulation and targeted ROS-mediated killing in situ. By exploiting these tunable properties and selective binding to fungi, localized antifungal activity is achieved using in vivo-like cell spheroid and animal tissue infection models. Structured nanozyme assemblies are directed to Candida-infected sites using programmable algorithms to perform precisely guided spatial targeting and on-site catalysis resulting in fungal eradication within 10 min. This nanozyme-based microrobotics approach provides a uniquely effective and targeted therapeutic modality for pathogen elimination at the infection site.
Assuntos
Antifúngicos , Micoses , Animais , Antifúngicos/química , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Candida albicans/metabolismo , Modelos AnimaisRESUMO
Sufficient alveolar bone is a safeguard for achieving desired outcomes in orthodontic treatment. Moving a tooth into an alveolar bony defect may result in a periodontal defect or worse-tooth loss. Therefore, when facing a pathologic situation such as periodontal bone loss, alveolar clefts, long-term tooth loss, trauma, and thin phenotype, bone grafting is often necessary to augment bone for orthodontic treatment purposes. Currently, diverse bone grafts are used in clinical practice, but no single grafting material shows absolutely superior results over the others. All available materials demonstrate pros and cons, most notably donor morbidity and adverse effects on orthodontic treatment. Here, we review newly developed graft materials that are still in the pre-clinical stage, as well as new combinations of existing materials, by highlighting their effects on alveolar bone regeneration and orthodontic tooth movement. In addition, novel manufacturing techniques, such as bioprinting, will be discussed. This mini-review article will provide state-of-the-art information to assist clinicians in selecting grafting material(s) that enhance alveolar bone augmentation while avoiding unfavorable side effects during orthodontic treatment.
RESUMO
Bacteria and fungi can interact to form inter-kingdom biofilms in the oral cavity. Streptococcus mutans and Candida albicans are frequently detected in saliva and in dental biofilms associated with early childhood caries (tooth-decay), a prevalent oral disease induced by dietary sugars. However, how different sugars influence this bacterial-fungal interaction remains unclear. Here, we investigate whether specific sugars affect the inter-kingdom interaction in saliva and subsequent biofilm formation on tooth-mimetic surfaces. The microbes were incubated in saliva containing common dietary sugars (glucose and fructose, sucrose, starch, and combinations) and analyzed via fluorescence imaging and quantitative computational analyses. The bacterial and fungal cells in saliva were then transferred to hydroxyapatite discs (tooth mimic) to allow microbial binding and biofilm development. We found diverse bacterial-fungal aggregates which varied in size, structure, and spatial organization depending on the type of sugars. Sucrose and starch+sucrose induced the formation of large mixed-species aggregates characterized by bacterial clusters co-bound with fungal cells, whereas mostly single-cells were found in the absence of sugar or in the presence of glucose and fructose. Notably, both colonization and further growth on the apatitic surface were dependent on sugar-mediated aggregation, leading to biofilms with distinctive spatial organizations and 3D architectures. Starch+sucrose and sucrose-mediated aggregates developed into large and highly acidogenic biofilms with complex network of bacterial and fungal cells (yeast and hyphae) surrounded by an intricate matrix of extracellular glucans. In contrast, biofilms originated from glucose and fructose-mediated consortia (or without sugar) were sparsely distributed on the surface without structural integration, growing predominantly as individual species with reduced acidogenicity. These findings reveal the impact of dietary sugars on inter-kingdom interactions in saliva and how they mediate biofilm formation with distinctive structural organization and varying acidogenicity implicated with human tooth-decay.
Assuntos
Açúcares da Dieta , Saliva , Pré-Escolar , Humanos , Saliva/microbiologia , Apatitas , Streptococcus mutans , Biofilmes , Sacarose/farmacologia , Amido/farmacologia , Frutose , GlucoseRESUMO
Objective: To determine if oral health indicators (dental caries experience andperiodontitis) associate with mental and cardiovascular health issues in AsianAmericans. Methods: Medical history data, dental caries experience (DMFT andDMFS; Decayed, Missing due to caries, Filled Teeth/Surface), and periodontitisstatus of Asian Americans were obtained from the Dental Registry and DNARepository at University of Pittsburgh School of Dental Medicine. A total of 6,117individuals were evaluated and among which dental status of 309 Asian Americansubjects (292 adults and 17 children under the age of twelve) were analyzed. Thefrequency of mental health issues and hypertension depending on dental cariesexperience (Decayed, Missing due to caries, Filled Teeth or Surfaces, DMFT/DMFS)and periodontitis were evaluated and chi-square or Fisher's exact test were usedwith an alpha of 0.05 to determine statistical differences. Results: For the 292Asian American adult subjects, the mean DMFT was 10.1 and mean DMFS was 27.5,which is similar to the expected values in adult DMFT (9.0-11.3) for the UnitedStates. For the 17 Asian American children subjects under age of twelve, the meanDMFT was 1.8 and mean DMFS was 3.8, which also fell into the expected values forchildren DMFT for the United States (1.2-2.6). More severe dental caries experiencewas associated with having an underlying mental health issue (p=0.02) andhypertension (p=0.02). No associations between having periodontitis and mentalor cardiovascular issues were found in the cohort. Conclusion: More severe dentalcaries experience of Asian Americans associate with mental and cardiovascularissues.
Objetivo: Determinar se medidas de saúde oral (cárie dentária e periodontite)estão associadas com doenças cardiovasculares e mentais em asiáticosamericanos. Métodos: Dados de saúde, experiência de cárie (CPOD e CPOS) eperiodontitie de asiáticos americanos foram obtidos do Registro Odontológico eRepositório de DNA da Universidade de Pittsburgh. O total de 6.117 pessoas estavadisponível no registro e 309 asiáticos americanos foram estudados (292 adultos e17 crianças abaixo de 12 anos). As frequências de doença mental e hipertensão,dependendo da experiência de cárie e periodontite, foram avaliadas e os testesqui-quadrado e exato de Fisher foram usados com alfa de 0,05 para determinardiferenças estatísticas. Resultados: A média de CPOD dos 292 adultos foi de 10,1e a média de CPOS foi 27,5, o que é parecido com os valores esperados de CPODde adultos nos Estados Unidos (9,0-11,3). A média de CPOD das 17 crianças menoresde 12 anos foi 1,8 e a do CPOS foi 3,8, o que também é similar aos valores de CPODem crianças dos Estaods Unidos (1,2-2,6). Experiência de cárie mais severaassociou-se com ter problema de saúde mental (p=0,02) e hipertensão (p=0,02).Não se encontrou associação entre periodontite e problemas mentais oucardiovasculares na amostra. Conclusão: Experiência de cárie mais severa emasiáticos americanos associa-se com doença mental e cardiovascular.