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10.
J Endod ; 44(11): 1665-1670, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30409447

RESUMEN

INTRODUCTION: The outcomes of an immature tooth with necrotic pulp treated with regenerative endodontic procedures (REPs) were assessed clinically and radiographically. Root maturation is an important outcome of REPs, and several radiographic measurement methods have been used to measure this. The aim of this study was to compare radiographic measurement methods, measuring root maturation in immature teeth with necrotic pulp treated with REPs. METHODS: Seventy-one radiographic images of REP cases were measured and compared using 3 radiographic measurement methods described by Bose et al (2009), Alobaid et al (2014), and Flake et al (2014). The intraclass correlation coefficient values were evaluated using the intra- and interobserver reliability test and the effect of the stage of root development. RESULTS: The intra- and interobserver reliability for Alobaid et al's method and Flake et al's method were slightly higher than Bose et al's method as quantified by the intraclass correlation coefficient without a significant difference (P > .05). The stage of root development did not affect the reliability of the measurement methods. A high level of agreement was found among the 3 stages of root development for all 3 quantitative radiographic measurement methods. CONCLUSIONS: All 3 quantitative radiographic measurement methods exhibited high agreement regarding reliability. The stage of root development did not have an impact on the reliability of the measurement methods.


Asunto(s)
Radiografía Dental/métodos , Endodoncia Regenerativa/métodos , Raíz del Diente/diagnóstico por imagen , Raíz del Diente/crecimiento & desarrollo , Diente no Vital/diagnóstico por imagen , Necrosis de la Pulpa Dental/terapia , Humanos , Reproducibilidad de los Resultados
11.
J Endod ; 44(8): 1270-1275, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29935871

RESUMEN

INTRODUCTION: In regenerative endodontic treatment (RET), practitioners favor the placement of bioceramics as sealing materials over blood clots. It is important to understand the interaction between sealing material and cells in the root canal. The purpose of this study was to compare the effectiveness of various bioceramic materials (ProRoot MTA [Dentsply, Tulsa, OK], Biodentine [Septodont, Saint-Maur-des-Fossés, France], and RetroMTA [BioMTA, Seoul, Korea]) as sealing materials in RET for the proliferation and differentiation of stem cells from the apical papilla (SCAPs). METHODS: SCAPs were seeded at 20,000 cells/well and cultured with soluble agents of testing materials through a transwell culture plate. The proliferation of SCAPs was investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on days 1, 3, 7, and 14 of testing. Alizarin red staining and quantitative real-time polymerase chain reaction were used for SCAP differentiation at different time points (1, 7, 14, and 21 days). The odontoblast genes expressed are dentin matrix acidic phosphoprotein 1, dentin sialophosphoprotein, osteocalcin, and matrix extracellular phosphoglycoprotein, which were used in this study. The SCAPs were cultured in odonto/osteogenic induction medium and also contacted soluble agents from the testing materials. RESULTS: All 3 tested biomaterials induced SCAP proliferation. The Biodentine, ProRootMTA, and RetroMTA groups showed significant SCAP proliferation on days 7 and 14 compared with the control. In regard to odontoblastic differentiation, only Biodentine showed positive alizarin red staining. The highest expressions of dentin matrix acidic phosphoprotein 1, dentin sialophosphoprotein, and matrix extracellular phosphoglycoprotein were found on day 21 in the Biodentine group. The expression of osteocalcin was found to be significant on day 7. CONCLUSIONS: Biodentine, ProRootMTA, and RetroMTA can induce SCAP proliferation. Biodentine induced significant SCAP differentiation among the 3 materials.


Asunto(s)
Materiales Biocompatibles/farmacología , Cerámica/farmacología , Papila Dental/efectos de los fármacos , Odontoblastos/efectos de los fármacos , Células Madre/efectos de los fármacos , Ápice del Diente/citología , Compuestos de Aluminio/farmacología , Compuestos de Calcio/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Papila Dental/citología , Papila Dental/crecimiento & desarrollo , Papila Dental/fisiología , Combinación de Medicamentos , Humanos , Odontoblastos/citología , Odontoblastos/fisiología , Óxidos/farmacología , Endodoncia Regenerativa/métodos , Materiales de Obturación del Conducto Radicular/farmacología , Silicatos/farmacología , Células Madre/fisiología , Ápice del Diente/efectos de los fármacos , Ápice del Diente/crecimiento & desarrollo , Ápice del Diente/fisiología
12.
PLoS One ; 12(10): e0186888, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29084244

RESUMEN

Chemotherapy induced peripheral neuropathy (CIPN), a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described. Studies from animal models have suggested a number of disease etiologies including mitotoxicity, axonal degeneration, immune signaling, and reduced sensory innervations but these outcomes are the result of prolonged treatment paradigms and do not necessarily represent the early formative events associated with CIPN. Here we show that acute exposure to vinca alkaloids results in an immediate pain syndrome in both flies and mice. Furthermore, we demonstrate that exposure of isolated sensory neurons to vinca alkaloids results in the generation of an inward sodium current capable of depolarizing these neurons to threshold resulting in neuronal firing. These neuronal effects of vinca alkaloids require the transient receptor potential ankyrin-1 (TrpA1) channel, and the hypersensitization to painful stimuli in response to the acute exposure to vinca alkaloids is reduced in TrpA1 mutant flies and mice. These findings demonstrate the direct excitation of sensory neurons by CIPN-causing chemotherapy drugs, and identify TrpA1 as an important target during the pathogenesis of CIPN.


Asunto(s)
Dolor/fisiopatología , Células Receptoras Sensoriales/efectos de los fármacos , Canal Catiónico TRPA1/metabolismo , Alcaloides de la Vinca/farmacología , Animales , Humanos , Ratones
13.
J Endod ; 43(9S): S95-S101, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28844309

RESUMEN

Regenerative endodontic procedures (REPs) have been shown to promote the resolution of signs and symptoms of disease and increase survival compared with traditional treatment procedures. However, there is still variable predictability of continued root development and evidence that the tissues formed do not recapitulate the native pulp-dentin complex. There is growing evidence that the apical papilla is capable of surviving prolonged endodontic infection and apical periodontitis and that it represents a rich source of undifferentiated mesenchymal stem cells in REPs. The survival and proper differentiation of stem cells transferred into infected root canals are fraught with challenges. Residual antigens, such as lipopolysaccharides, have been shown to be present in dentin even after adequate chemomechanical debridement. These antigens have a profound effect on stem cell fate by modulating their proliferative capacity and postdifferentiation phenotype. Thus, root canals must be detoxified in addition to disinfection. There is a strong need for translational studies that incorporate all aspects of tissue engineering in endodontics in models that include an existing infection to promote further advancement of the field. This is particularly important to make REPs more predictable when treating immature teeth in young patients. Importantly, regenerative procedures could eventually promote tooth longevity in our aging population. Lessons learned from translational studies that best mimic the clinical challenges could be evaluated in pragmatic clinical trials to determine the effectiveness of these procedures to promote desirable patient-centered outcomes.


Asunto(s)
Pulpa Dental/fisiología , Endodoncia/métodos , Endodoncia/tendencias , Regeneración , Células Madre/microbiología , Ingeniería de Tejidos , Predicción , Humanos
14.
J Am Dent Assoc ; 147(5): 372-80, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27017182

RESUMEN

BACKGROUND AND OVERVIEW: Immature teeth are susceptible to infections due to trauma, anatomic anomalies, and caries. Traditional endodontic therapies for immature teeth, such as apexification procedures, promote resolution of the disease and prevent future infections. However, these procedures fail to promote continued root development, leaving teeth susceptible to fractures. Regenerative endodontic procedures (REPs) have evolved in the past decade, being incorporated into endodontic practice and becoming a viable treatment alternative for immature teeth. The authors have summarized the status of regenerative endodontics on the basis of the available published studies and provide insight into the different levels of clinical outcomes expected from these procedures. CONCLUSIONS: Substantial advances in regenerative endodontics are allowing a better understanding of a multitude of factors that govern stem cell-mediated regeneration and repair of the damaged pulp-dentin complex. REPs promote healing of apical periodontitis, continued radiographic root development, and, in certain cases, vitality responses. Despite the clinical success of these procedures, they appear to promote a guided endodontic repair process rather than a true regeneration of physiological-like tissue. PRACTICAL IMPLICATIONS: Immature teeth with pulpal necrosis with otherwise poor prognosis can be treated with REPs. These procedures do not preclude the possibility of apexification procedures if attempts are unsuccessful. Therefore, REPs may be considered first treatment options for immature teeth with pulpal necrosis.


Asunto(s)
Necrosis de la Pulpa Dental/terapia , Endodoncia/tendencias , Apexificación , Pulpa Dental , Humanos , Regeneración
15.
J Neurosci ; 35(22): 8593-603, 2015 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-26041925

RESUMEN

Nerve growth factor (NGF) is elevated in certain chronic pain conditions and is a sufficient stimulus to cause lasting pain in humans, but the actual mechanisms underlying the persistent effects of NGF remain incompletely understood. We developed a rat model of NGF-induced persistent thermal hyperalgesia and mechanical allodynia to determine the role of transient receptor potential vanilloid 1 (TRPV1) and oxidative mechanisms in the persistent effects of NGF. Persistent thermal hypersensitivity and mechanical allodynia require de novo protein translation and are mediated by TRPV1 and oxidative mechanisms. By comparing effects after systemic (subcutaneous), spinal (intrathecal) or hindpaw (intraplantar) injections of test compounds, we determined that TRPV1 and oxidation mediate persistent thermal hypersensitivity via peripheral and spinal sites of action and mechanical allodynia via only a spinal site of action. Therefore, NGF-evoked thermal and mechanical allodynia are mediated by spatially distinct mechanisms. NGF treatment evoked sustained increases in peripheral and central TRPV1 activity, as demonstrated by increased capsaicin-evoked nocifensive responses, increased calcitonin gene-related peptide release from hindpaw skin biopsies, and increased capsaicin-evoked inward current and membrane expression of TRPV1 protein in dorsal root ganglia neurons. Finally, we showed that NGF treatment increased concentrations of linoleic and arachidonic-acid-derived oxidized TRPV1 agonists in spinal cord and skin biopsies. Furthermore, increases in oxidized TRPV1-active lipids were reduced by peripheral and spinal injections of compounds that completely blocked persistent nociception. Collectively, these data indicate that NGF evokes a persistent nociceptive state mediated by increased TRPV1 activity and oxidative mechanisms, including increased production of oxidized lipid TRPV1 agonists.


Asunto(s)
Factor de Crecimiento Nervioso/farmacología , Nocicepción/efectos de los fármacos , Nocicepción/fisiología , Estrés Oxidativo/fisiología , Canales Catiónicos TRPV/metabolismo , Potenciales de Acción/efectos de los fármacos , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Capsaicina/farmacología , Células Cultivadas , Cicloheximida/farmacología , Ensayo de Inmunoadsorción Enzimática , Ganglios Espinales/citología , Hiperalgesia/etiología , Masculino , Estrés Oxidativo/efectos de los fármacos , Dimensión del Dolor , Inhibidores de la Síntesis de la Proteína/farmacología , Ratas , Ratas Sprague-Dawley , Células Receptoras Sensoriales/efectos de los fármacos , Fármacos del Sistema Sensorial/farmacología , Piel/inervación
16.
J Endod ; 41(5): 663-70, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25687363

RESUMEN

INTRODUCTION: Scaffolds often fail to mimic essential functions of the physiologic extracellular matrix (ECM) that regulates cell-cell communication in tissue microenvironments. The development of scaffold-free microtissues containing stem cell-derived ECM may serve as a successful alternative to the use of artificial scaffolds. The current study aimed to fabricate 3-dimensional microtissue spheroids of dental pulp cells (DPCs) prevascularized by human umbilical vein endothelial cells (HUVECs) and to characterize these scaffold-free spheroids for the in vitro formation of pulplike tissue constructs. METHODS: Three-dimensional microtissue spheroids of DPC alone and DPC-HUVEC co-cultures were fabricated using agarose micro-molds. Cellular organization within the spheroids and cell viability (live/dead assay) were assessed at days 1, 7, and 14. Microtissue spheroids were allowed to self-assemble into macrotissues, induced for odontogenic differentiation (21 days), and examined for expression levels of osteo/odontogenic markers: alkaline phosphatase, bone sialoprotein and RUNX2 (Real-time PCR), mineralization (von-Kossa), and prevascularisation (immunohistochemistry for CD31). RESULTS: The DPC microtissue microenvironment supported HUVEC survival and capillary network formation in the absence of a scaffolding material and external angiogenic stimulation. Immunohistochemical staining for CD31 showed the capillary network formed by HUVECs did sustain-for a prolonged period-even after the microtissues transformed into a macrotissue. Induced, prevascularized macrotissues showed enhanced differentiation capacity compared with DPC alone macrotissues, as shown by higher osteo/odontogenic gene expression levels and mineralization. CONCLUSIONS: These findings provide insight into the complex intercellular cross talk occurring between DPCs and HUVECs in the context of angiogenesis and pulp regeneration and highlight the significance of developing a favorable 3-dimensional microenvironment that can, in turn, contribute toward successful pulp regeneration strategies.


Asunto(s)
Pulpa Dental/citología , Células Endoteliales/fisiología , Esferoides Celulares/fisiología , Ingeniería de Tejidos/métodos , Comunicación Celular , Células Cultivadas , Técnicas de Cocultivo , Humanos , Venas Umbilicales
17.
Tissue Eng Part A ; 21(3-4): 550-63, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25203774

RESUMEN

Securing an adequate blood supply for the survival of cell transplants is critical for a successful outcome in tissue engineering. Interactions between endothelial and progenitor/stem cells are important for vascularization of regenerating tissue. Recently, self-assembling peptide nanofibers were described as a promising environment for pulp regeneration due to their synthetic nature and controlled physicochemical properties. In this study, the peptide hydrogel PuraMatrix™ was used as a scaffold system to investigate the role of dental pulp stem cells (DPSCs) in triggering angiogenesis and the potential for regenerating vascularized pulp in vivo. Human umbilical vein endothelial cells (HUVECs), DPSCs, or cocultures of both cell types were encapsulated in three-dimensional PuraMatrix. The peptide nanofiber microenvironment supported cell survival, cell migration, and capillary network formation in the absence of exogenous growth factors. DPSCs increased early vascular network formation by facilitating the migration of HUVECs and by increasing vascular endothelial growth factor (VEGF) expression. Both the DPSC-monoculture and coculture groups exhibited vascularized pulp-like tissue with patches of osteodentin after transplantation in mice. The cocultured groups exhibited more extracellular matrix, vascularization, and mineralization than the DPSC-monocultures in vivo. The DPSCs play a critical role in initial angiogenesis, whereas coordinated efforts by the HUVECs and DPSCs are required to achieve a balance between extracellular matrix deposition and mineralization. The findings of this study also highlighted the importance of a microenvironment that supports cell-cell interactions and cell migration, which contribute to successful dental pulp regeneration.


Asunto(s)
Pulpa Dental/citología , Pulpa Dental/crecimiento & desarrollo , Células Endoteliales/citología , Neovascularización Fisiológica/fisiología , Péptidos/administración & dosificación , Células Madre/citología , Adolescente , Adulto , Animales , Comunicación Celular/fisiología , Diferenciación Celular , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Pulpa Dental/irrigación sanguínea , Células Endoteliales/fisiología , Femenino , Humanos , Hidrogeles/administración & dosificación , Hidrogeles/química , Inyecciones , Masculino , Ensayo de Materiales , Ratones , Péptidos/química , Regeneración/fisiología , Trasplante de Células Madre , Células Madre/fisiología , Adulto Joven
18.
J Endod ; 40(7): 891-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24935531

RESUMEN

INTRODUCTION: Effective root canal disinfection is a fundamental component of successful root canal treatment. Photodynamic therapy (PDT) has been proposed as a new adjunctive method for additional disinfection of the root canal system with the possibility of improved treatment outcomes. The aim of this systematic review was to investigate the effect of PDT on bacterial load reduction during root canal disinfection. METHODS: Two reviewers independently conducted a comprehensive literature search using a combination of medical subject heading terms and key words to identify studies relevant to the Population Intervention Control Outcome question. The selection of articles for inclusion was performed in 2 phases based on predetermined eligibility criteria according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inter-reviewer agreement for each phase was recorded. The effect of PDT on bacterial load reduction during root canal disinfection was evaluated as the primary outcome variable during data extraction. RESULTS: The literature search provided 57 titles and abstracts. Three articles met the inclusion criteria and were selected for this systematic review. The reasons for study exclusion in each phase were recorded. Because of the heterogeneity in clinical indications and PDT protocols among the included studies, a meta-analysis could not be performed. All included studies showed a positive effect of PDT in the reduction of microbial load in root canal treatment ranging from 91.3%-100%. CONCLUSIONS: Limited clinical information is currently available on the use of PDT in root canal disinfection. If supported by future clinical research, PDT may have efficacy for additional root canal disinfection, especially in the presence of multi-drug-resistant bacteria.


Asunto(s)
Cavidad Pulpar/microbiología , Desinfección/métodos , Fotoquimioterapia/métodos , Irrigantes del Conducto Radicular/uso terapéutico , Preparación del Conducto Radicular/métodos , Carga Bacteriana/efectos de los fármacos , Terapia Combinada/métodos , Cavidad Pulpar/efectos de los fármacos , Humanos
19.
J Endod ; 40(4 Suppl): S52-7, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24698694

RESUMEN

The endodontic management of permanent immature teeth is fraught with challenges. Although treatment modalities for vital pulp therapy in these teeth provide long-term favorable outcome, the outcomes from the treatment of pulp necrosis and apical periodontitis are significantly less predictable. Immature teeth diagnosed with pulp necrosis have been traditionally treated with apexification or apexogenesis approaches. Unfortunately, these treatments provide little to no benefit in promoting continued root development. Regenerative endodontic procedures have emerged as an important alternative in treating teeth with otherwise questionable long-term prognosis because of thin, fragile dentinal walls and a lack of immunocompetency. These procedures rely heavily on root canal chemical disinfection of the root canal system. Traditionally, irrigants and medicaments have been chosen for their maximum antimicrobial effect without consideration for their effects on stem cells and the dentinal microenvironment. Translational research has been crucial to provide evidence for treatment modifications that aim to increase favorable outcome while steering away from common pitfalls in the currently used protocols. In this review, recent advances learned from translational research related to disinfection in regenerative endodontics are presented and discussed.


Asunto(s)
Enfermedades de la Pulpa Dental/terapia , Desinfección/métodos , Tratamiento del Conducto Radicular/métodos , Apexificación/métodos , Microambiente Celular/fisiología , Pulpa Dental/fisiología , Dentina/fisiología , Humanos , Regeneración/fisiología , Irrigantes del Conducto Radicular/uso terapéutico , Células Madre/fisiología , Investigación en Medicina Traslacional
20.
J Endod ; 40(4 Suppl): S65-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24698697

RESUMEN

Regenerative endodontic procedures are rapidly gaining the attention of clinicians and investigators alike. However, it is often challenging to understand various regenerative studies and to interpret their results. The present review addresses this problem by focusing on recent strategies for developing standardized clinical protocols, understanding the full spectrum of clinical and translational research and its relationship to selection of proper outcome measures, as well as reviewing the fundamental role of paradigms in designing and interpreting regenerative studies.


Asunto(s)
Enfermedades de la Pulpa Dental/terapia , Pulpa Dental/fisiología , Regeneración/fisiología , Proyectos de Investigación , Protocolos Clínicos/normas , Endodoncia/normas , Odontología Basada en la Evidencia , Humanos , Proyectos de Investigación/normas
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