RESUMEN
The aim of this study was to evaluate the release of simvastatin from scaffolds composed of poly(lactic-co-glycolic) acid (PLGA) and biphasic ceramic designed for bone engineering and to assess the physico-chemical and mechanical properties of the scaffolds. Samples with 30% and 70% porosity were obtained with 0, 2, 5, and 8 wt %. of simvastatin through the solvent evaporation technique and leaching of sucrose particles. Scaffold degradation and simvastatin release were evaluated in phosphate-buffered saline. Scaffolds were analyzed by scanning electron microscopy and microtomography for two-dimensional and three-dimensional morphological characterization of the porosity, connectivity, and intrinsic permeability. The mechanical characterization was conducted based on the compressive strength and the chemical characterization by differential scanning calorimetry and energy dispersive X-ray spectroscopy. Gradual and prolonged simvastatin release from the scaffolds was observed. The release followed the Korsmeyer kinetics model with the predominance of case II transport for 30% porosity scaffolds, and anomalous behavior for the 70% porosity samples. Simvastatin release was also influenced by the slow scaffold degradation due to the strong chemical interaction between simvastatin and PLGA, as observed by differential scanning calorimetry. The scaffolds presented spherical and sucrose crystal-shaped pores that resulted in a homogenous porosity, with a predominance of open pores, ensuring interconnectivity. Simvastatin incorporation into the scaffolds and increased porosity did not influence the mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties, a promise for applications in bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2152-2164, 2019.
Asunto(s)
Regeneración Ósea , Cerámica/química , Hidroxiapatitas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Simvastatina , Animales , Implantes de Medicamentos/química , Implantes de Medicamentos/farmacocinética , Humanos , Simvastatina/química , Simvastatina/farmacocinéticaRESUMEN
OBJECTIVES: The aim of the present study was to assess the psychometric properties and level of agreement between the self-administered and interviewer-administered Child Perceptions Questionnaire (CPQ) for children between 8 and 10 years of age (CPQ(8-10) ) and between 11 and 14 (CPQ(11-14) ) years of age. METHODS: A randomized cross-over study was carried out, involving 180 children (Group 1 - 90 children between 8 and 10; Group 2 - 90 children between 11 and 14 years of age) in the state of Minas Gerais, Brazil. All children completed both administration modes of the CPQ; half of each group received interviewer-administered mode first [Subgroup A (CPQ(8-10) n = 45) and Subgroup C (CPQ(11-14) n = 45)], and the other half performed the self-administered mode first [Subgroup B (CPQ(8-10) n = 45) and Subgroup D (CPQ(11-14) n = 45)]. Test-retest reliability of each mode of administration was tested on 60 children (30 for CPQ(8-10) ; 30 for CPQ(11-14) ), who were not included in the other analyses. The level of agreement between scores on the self-administered and interviewer-administered versions of the CPQ(8-10) and CPQ(11-14) was established using the intraclass correlation coefficient (ICC). The order of presentation of both instruments was tested considering the four subgroups (A, B, C and D). The calculation of effect size proposed by Cohen (1992) was used to test the clinical significance of the findings. RESULTS: Both the self-administered and interviewer-administered versions of CPQ(8-10) and CPQ(11-14) demonstrated acceptable psychometric properties. Agreement between the administration modes for the CPQ(8-10) and CPQ(11-14) was 0.90 and 0.88 (ICC), respectively. With the exception of the functional limitation subscale, the scores of the subscales and overall score on the CPQ(8-10) were significantly higher in the group of children who responded to the interviewer-administered measure first. With the CPQ(11-14) , statistically significant differences were found only for the emotional well-being subscale. CONCLUSIONS: Both administration modes of the CPQ(8-10) and CPQ(11-14) demonstrated satisfactory psychometric properties and a high level of agreement. Although statistically significant differences were observed for oral symptoms, emotional well-being and social well-being, with the first administration of the interviewer-administered version, the effect of the order of administration had small to medium effects on the CPQ scores.
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Encuestas de Salud Bucal/métodos , Salud Bucal/estadística & datos numéricos , Adolescente , Actitud Frente a la Salud , Brasil , Niño , Estudios Cruzados , Femenino , Humanos , Entrevistas como Asunto , Masculino , Psicometría , Calidad de Vida/psicología , Autoevaluación (Psicología) , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Mineral trioxide aggregate (MTA) and calcium hydroxide [Ca(OH)(2)] are promising biomaterials for stimulating dentinogenesis and cementogenesis. This research was undertaken to understand how MTA and CA(OH)(2) participate in the inflammatory, healing, and biomineralization processes. In this part of the study, we evaluated inflammatory signaling molecules promoted by in vivo host interaction with MTA and Ca(OH)(2). METHODS: Human dentin tubes were filled with ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK), Ca(OH)(2), or kept empty. After 12 hours and 1, 3, 7, 15, 30, and 60 days of implantation in subcutaneous tissues in the backs of mice, the tubes and surrounding tissues were retrieved for cytokine level quantification and histological and immunohistochemical analysis. RESULTS: MTA and Ca(OH)(2) induced proinflammatory cytokine up-regulation for up to 3 days. Moreover, interleukin-10 overexpression was noted on the tissue in contact with the biomaterials during the acute phase of the inflammatory reaction. Immunohistochemical analyses showed an increased expression of myeloperoxidase, nuclear factor kappa B (NF-κB), cyclooxygenase-2, inducible nitric oxide synthase enzymes, and vascular endothelial growth factor on day 1 for all groups. CONCLUSIONS: MTA and Ca(OH)(2) increased the activation of the NF-κB signaling system on day 1 for all groups. This finding can be associated with a proinflammatory and pro-wound healing environment, which was promoted earlier by MTA.
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Compuestos de Aluminio , Compuestos de Calcio , Hidróxido de Calcio , Inflamación/metabolismo , Óxidos , Materiales de Obturación del Conducto Radicular , Transducción de Señal , Silicatos , Animales , Calcificación Fisiológica , Ciclooxigenasa 2/biosíntesis , Combinación de Medicamentos , Humanos , Interleucina-10/biosíntesis , Interleucina-1beta/biosíntesis , Ratones , FN-kappa B/biosíntesis , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Peroxidasa/biosíntesis , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Cicatrización de Heridas/fisiologíaRESUMEN
BACKGROUND: Physiological root resorption differentiates primary from permanent teeth. The understanding of what protects and regulates root resorption might help to develop therapies to its control. AIM: To verify the presence and distribution of ECRM and the expression of CK14, OPG, TRAP and COX-2 in the periodontal ligament (PDL) of human primary and permanent teeth. Design. Eight primary teeth undergoing physiological or pathological root resorption and 4 permanent teeth were immunohistochemically processed for CK14, TRAP, COX-2 and OPG expression. RESULTS: PDL from primary and permanent teeth showed similar morphological features; however, fewer ECRM clusters and higher immunoreactivity to CK14 were found in primary PDL. In permanent teeth, ECRM were distributed along the entire PDL tissue. Howship's lacunae were found only in primary teeth, associated with the presence of TRAP-positive cells and increase in COX-2 expression. OPG expression in primary PDL was detected in nonresorptive cervical areas and in lacunae showing reparative tissue. It was observed higher expression of OPG in all permanent teeth when compared to primary specimens. CONCLUSIONS: It may be concluded that PDL from primary teeth shows less ECRM clusters and lower expression of OPG. These features may be associated with lower protection against root resorption in primary teeth.
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Ligamento Periodontal/metabolismo , Resorción Radicular/prevención & control , Diente Primario/fisiología , Fosfatasa Ácida/biosíntesis , Fosfatasa Ácida/genética , Adulto , Niño , Preescolar , Ciclooxigenasa 2/biosíntesis , Ciclooxigenasa 2/genética , Dentición Permanente , Células Epiteliales/fisiología , Expresión Génica , Humanos , Isoenzimas/biosíntesis , Isoenzimas/genética , Queratina-14/biosíntesis , Queratina-14/genética , Osteoprotegerina/biosíntesis , Osteoprotegerina/genética , Resorción Radicular/metabolismo , Resorción Radicular/fisiopatología , Fosfatasa Ácida Tartratorresistente , Diente Primario/citología , Adulto JovenRESUMEN
Stem cells constitute the source of differentiated cells for the generation of tissues during development, and for regeneration of tissues that are diseased or injured postnatally. In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that span from Alzheimer's disease to cardiac ischemia to bone or tooth loss. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental pulp is considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that dental pulp stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The dental pulp stem cells are highly proliferative. This characteristic facilitates ex vivo expansion and enhances the translational potential of these cells. Notably, the dental pulp is arguably the most accessible source of postnatal stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration. This review discusses fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry.
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Células Madre Adultas , Pulpa Dental/citología , Células Madre Mesenquimatosas , Regeneración , Ingeniería de Tejidos , Animales , Humanos , Péptidos y Proteínas de Señalización Intercelular/fisiología , Células Madre Multipotentes , Neovascularización Fisiológica/fisiología , Andamios del TejidoRESUMEN
INTRODUCTION: The biological processes underlying the ability of mineral trioxide aggregate (MTA) to promote hard-tissue deposition and wound healing remain unclear. To further study these processes, specific signaling molecules related to the inflammatory response and the biomineralization process were analyzed to assess host-MTA interactions in vivo. METHODS: For cytokine level quantification and immunohistochemical analysis, human dentin tubes were filled with ProRoot MTA (Dentsply, Tulsa Dental, OK) or kept empty and were implanted in subcutaneous tissues in the backs of mice. Dentin tubes were retrieved and subsequently observed using a scanning electron microscope. RESULTS: MTA induced a time-dependent proinflammatory cytokine up-regulation up to 3 days. Immunohistochemical analyses showed an up-regulated expression of myeloperoxidase, nuclear factor-kappa B, activating protein-1, cyclooxygenase-2, inducible nitric oxide synthase, and vascular endothelial growth factor on day 1. Scanning electron microscopic examination revealed the presence of apatite-like clusters on collagen fibrils over the surface of tubes containing MTA. With the increase in time after implantation, a more extensive mineralization showing a compact layer of apatite was observed. CONCLUSION: MTA induced a proinflammatory and pro-wound healing environment. The biomineralization process occurred simultaneously at the biomaterial-dentin-tissue interface, with the acute inflammatory response. This promoted the integration of the biomaterial into the environment.
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Compuestos de Aluminio/farmacología , Calcificación Fisiológica/efectos de los fármacos , Compuestos de Calcio/farmacología , Mediadores de Inflamación/metabolismo , Óxidos/farmacología , Materiales de Obturación del Conducto Radicular/farmacología , Transducción de Señal/efectos de los fármacos , Silicatos/farmacología , Animales , Apatitas/análisis , Colágeno/efectos de los fármacos , Ciclooxigenasa 2/efectos de los fármacos , Dentina/ultraestructura , Combinación de Medicamentos , Humanos , Interleucina-10/análisis , Interleucina-1beta/efectos de los fármacos , Linfocitos/patología , Macrófagos/patología , Masculino , Ratones , FN-kappa B/efectos de los fármacos , Neutrófilos/patología , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Peroxidasa/efectos de los fármacos , Tejido Subcutáneo/efectos de los fármacos , Factores de Tiempo , Factor de Transcripción AP-1/efectos de los fármacos , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacosRESUMEN
AIM: The aim of this paper is to present a review and discussion of the current status of stem cell research with regard to tooth generation. BACKGROUND: Stem cells have been isolated from the pulp tissue of both deciduous and permanent teeth as well as from the periodontal ligament. Dental pulp stem cells demonstrate the capacity to form a dentin pulp-like complex in immunocompromised mice. A tooth-like structure was successfully formed, using a heterogeneous mixture of dental enamel epithelium, pulp mesenchymal cells, and scaffolds. CONCLUSION: The scientific community understands the need for more investigations to completely understand the conditions that would best favor the creation of a tooth substitute. Recent gains in the understanding of the molecular regulation of tooth morphogenesis, stem cell biology, and biotechnology offers the opportunity to realize this goal. CLINICAL SIGNIFICANCE: These findings, combined with the recent progress in stem cell research and tissue engineering, might allow the development of alternatives for current materials and therapies used to treat tooth tissue loss (e.g., enamel, dentin, pulp), reconstruct dentoalveolar and craniofacial bone defects, and eventually replace an entire tooth.
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Células Madre Adultas/citología , Células Madre Mesenquimatosas/citología , Odontogénesis/fisiología , Regeneración/fisiología , Diente/fisiología , Animales , Diferenciación Celular/fisiología , Pulpa Dental/citología , Humanos , Ratones , Ingeniería de Tejidos/métodosRESUMEN
Stem cells from human exfoliated deciduous teeth (SHED) have been isolated and characterized as multipotent cells. However, it is not known whether SHED can generate a dental pulp-like tissue in vivo. The purpose of this study was to evaluate morphologic characteristics of the tissue formed when SHED seeded in biodegradable scaffolds prepared within human tooth slices are transplanted into immunodeficient mice. We observed that the resulting tissue presented architecture and cellularity that closely resemble those of a physiologic dental pulp. Ultrastructural analysis with transmission electron microscopy and immunohistochemistry for dentin sialoprotein suggested that SHED differentiated into odontoblast-like cells in vivo. Notably, SHED also differentiated into endothelial-like cells, as demonstrated by B-galactosidase staining of cells lining the walls of blood-containing vessels in tissues engineered with SHED stably transduced with LacZ. This work suggests that exfoliated deciduous teeth constitute a viable source of stem cells for dental pulp tissue engineering.
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Pulpa Dental/irrigación sanguínea , Pulpa Dental/citología , Células Madre Multipotentes/trasplante , Neovascularización Fisiológica , Ingeniería de Tejidos , Animales , Diferenciación Celular , Células Cultivadas , Células Endoteliales/trasplante , Proteínas de la Matriz Extracelular/biosíntesis , Humanos , Operón Lac , Masculino , Ratones , Ratones SCID , Odontoblastos/citología , Fosfoproteínas , Regeneración , Sialoglicoproteínas , Andamios del Tejido , Diente Primario , Transducción Genética , beta-Galactosidasa/biosíntesisRESUMEN
Field cancerization involves the lateral spread of premalignant or malignant disease and contributes to the recurrence of head and neck tumors. The overall hypothesis underlying this work is that endothelial cells actively participate in tumor cell invasion by secreting chemokines and creating a chemotactic gradient for tumor cells. Here we demonstrate that conditioned medium from head and neck tumor cells enhance Bcl-2 expression in neovascular endothelial cells. Oral squamous cell carcinoma-3 (OSCC3) and Kaposi's sarcoma (SLK) show enhanced invasiveness when cocultured with pools of human dermal microvascular endothelial cells stably expressing Bcl-2 (HDMEC-Bcl-2), compared to cocultures with empty vector controls (HDMEC-LXSN). Xenografted OSCC3 tumors vascularized with HDMEC-Bcl-2 presented higher local invasion than OSCC3 tumors vascularized with control HDMEC-LXSN. CXCL1 and CXCL8 were upregulated in primary endothelial cells exposed to vascular endothelial growth factor (VEGF), as well as in HDMEC-Bcl-2. Notably, blockade of CXCR2 signaling, but not CXCR1, inhibited OSCC3 and SLK invasion toward endothelial cells. These data demonstrate that CXC chemokines secreted by endothelial cells induce tumor cell invasion and suggest that the process of lateral spread of tumor cells observed in field cancerization is guided by chemotactic signals that originated from endothelial cells.