The Self-assembling peptide P11-4 influences viability and osteogenic differentiation of stem cells of the apical papilla (SCAP).

OBJECTIVE: To analyze the effect of P11-4 self-assembly peptide on cell viability and osteogenic capacity of SCAPs through mineral deposition and gene expression of osteogenic markers. METHODS: SCAPs were seeded in contact with P11-4 (10 µg/ml, 100 µg/ml and 1 mg/ml) solution. Cell viability was evaluated using a colorimetric assay MTT: 3-(4,5-dimethyl-thiazolyl-2)-2,5- diphenyltetrazolium bromide) in an experimental time of 24, 48 and 72 h (n = 7). Mineral deposition and quantification provided by the cells was tested using the Alizarin Red staining and Cetylpyridinium Chloride (CPC), respectively, after 30 days (n = 4). Gene expression of Runt-related transcription factor 2 (RUNX2), Alkaline phosphatase (ALP) and Osteocalcin (OCN) was quantified using quantitative polymerase chain reaction (RT-qPCR), at 3 and 7 days with Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as the housekeeping gene, and relative gene expression was measured using the ΔΔCq method. Data were analyzed using Kruskall-Wallis followed by multiple comparisons, and T-test for gene expression with α=0.05. RESULTS: All tested concentrations (10 µg/ml, 100 µg/ml and 1 mg/ml) were not cytotoxic at time 24 and 48 h. After 72 h, a slight decrease in cell viability was observed for the lowest concentration (10 µg/ml). The concentration of 100 µg/ml P11-4 showed the highest mineral deposition. However, qPCR analysis of P11-4 (10 µg/ml) showed upregulation of RUNX2 and OCN at 3 days, with downregulation of ALP at 3 and 7d CONCLUSION: P11-4 did not affect cell viability, induced mineral deposition in SCAPs, and upregulated the expression of RUNX2 and OCN genes at 3 days, while downregulating ALP expression at 3 and 7 days. CLINICAL SIGNIFICANCE: Based on the results obtained in this study it can be stated that self-assembling peptide P11-4 is a potential candidate to induce mineralization on dental stem cells for regenerative purposes and also for a clinical use as a capping agent without compromising the cells health.

Tooth Formation: Are the Hardest Tissues of Human Body Hard to Regenerate?

With increasing life expectancy, demands for dental tissue and whole-tooth regeneration are becoming more significant. Despite great progress in medicine, including regenerative therapies, the complex structure of dental tissues introduces several challenges to the field of regenerative dentistry. Interdisciplinary efforts from cellular biologists, material scientists, and clinical odontologists are being made to establish strategies and find the solutions for dental tissue regeneration and/or whole-tooth regeneration. In recent years, many significant discoveries were done regarding signaling pathways and factors shaping calcified tissue genesis, including those of tooth. Novel biocompatible scaffolds and polymer-based drug release systems are under development and may soon result in clinically applicable biomaterials with the potential to modulate signaling cascades involved in dental tissue genesis and regeneration. Approaches for whole-tooth regeneration utilizing adult stem cells, induced pluripotent stem cells, or tooth germ cells transplantation are emerging as promising alternatives to overcome existing in vitro tissue generation hurdles. In this interdisciplinary review, most recent advances in cellular signaling guiding dental tissue genesis, novel functionalized scaffolds and drug release material, various odontogenic cell sources, and methods for tooth regeneration are discussed thus providing a multi-faceted, up-to-date, and illustrative overview on the tooth regeneration matter, alongside hints for future directions in the challenging field of regenerative dentistry.

Elaboración de un biodiente: enfoque actual y desafíos / Making a Bio-tooth: Current Approaches and Challenges

Antecedentes: El edentulismo es uno de los mayores problemas de salud oral que cause alteraciones fisiológicas, sociales, estéticas, fonéticas y nutricionales. Las terapias actuales para el remplazo dental son artificiales y no satisfacen los requisitos básicos de un diente natural. La bioingeniería de tejidos constituye una alternativa para la sustitución de dientes perdidos. Objetivo: Identificar los enfoques/técnicas disponibles actualmente para obtener un diente completo por bioingeniería (biodiente), así como puntualizar sus desafíos y perspectivas futuras. Métodos: Se realizó una revisión integrativa de la literatura, por medio de las siguientes palabras clave: biodiente, bioingeniería de tejidos, diente entero y células madre. Los años de la búsqueda fueron 2000-2018, en las bases de datos: PubMed, Scopus, EBSCO, Science Direct, Wiley Online Library, Lilacs y Google Académico/Scholar, en inglés y español. Se seleccionaron únicamente artículos y libros de mayor relevancia y pertinencia. Resultados: Se obtuvieron 53 artículos y 10 libros. Para la elaboración de un biodiente se emplean los siguientes métodos: andamios, sin andamios, células madre pluripotentes inducidas, germen de órganos, diente quimérico y estimulación de la formación de la tercera dentición. El tamaño y forma normales del diente, así como la obtención de células epiteliales, son los principales desafíos. Conclusiones: La posibilidad de crear y desarrollar un biodiente en un ambiente oral adulto es cada vez más real gracias a los avances biotecnológicos que ocurren diariamente. Es posible que estos conceptos sean la base de la odontología restauradora en un futuro próximo.

Background: Edentulism is one of the major oral health problems that cause physiological, social, aesthetic, phonetic, and nutritional issues. Current therapies for dental replacement are artificial and do not satisfy the basic requirements of a natural tooth. Tissue bioengineering could be a viable alternative to substitute lost teeth. Objective: To identify current available approaches/techniques to obtain a complete bioengineered tooth (bio-tooth) and to point out future challenges and perspectives. Methods: This was an integrative literature review. Search keywords used were: bio-tooth, tissue bioengineering, whole tooth, stem cells. The search included the years 2000 through 2018, using the databases PubMed, Scopus, EBSCO, Science Direct, Wiley Online Library, Lilacs and Google Scholar, both in English and Spanish. Only relevant and pertinent articles and books were selected. Results: 53 articles and 10 books were obtained. Methods for bio-tooth generation found were: scaffolds, scaffold-free, induced pluripotent stem cells, tooth organ germ, chimeric tooth, and stimulation of third dentition formation. Achieving normal tooth size and shape and obtaining epithelial cells are the main challenges. Conclusions: The possibility of creating and developing a whole bioengineered tooth (bio-tooth) in an adult oral environment is becoming more realistic, considering the daily biotechnological advances. It is possible that these concepts will be the basis of restorative dentistry in a near future.

Bioengineering of dental tissues: bibliometric analysis 2000-2011 / Bioingeniería de tejidos dentales: análisis bibliométrico 2000-2011

Introduction: There has been a noticeable increase in experimental use and therapies based on stem cells over recent years. Nevertheless, there is a lack of information about this progress in the dental field, which makes it difficult to trace development and design policies. The purpose of this study, as a first approach to the subject, is to determine a bibliometric profile for the investigation related to bioengineering of dental tissue at a worldwide scale, based on the MEDLINE database, for the period 2000-2011.Methodology: A bibliometric study was carried out. Every article indexed in the MEDLINE database and associated with the terms “stem cells” and “tooth regeneration” for the period 2000-2011 was included. The analyzed variables were publishing date, country of origin, language and publication type (original or review), journal, author, associated university and tissue source (human or animal). Results: For the entire period included in the study, 257 articles were found. Of these, 149 corresponded to original works published in English; 5 in other languages; 92 comprised literature reviews in English, 9 in other languages and 2 publications were included in the “others” category. The countries with the highest research productivity were the United States (24.51 percent, Japan (20.62 percent) and China (17.90 percent), while Brazil (3.9 percent) was the only Latin-American country found in the list. Animal tissues were used in 59.09 percent of them. The most productive authors were Ueda M (17) and Jin Y (11), whereas Fourth Military University (13), University of Tokyo (12) and Capital Medical University (10) had the largest number of publications. Conclusion: The United States, Japan and China concentrate about two thirds of the production. Latin-America was represented only by Brazil.

Introducción: El creciente uso experimental de células madres y el perfeccionamiento de las terapias con estas es un hecho notorio en los últimos años. Sin embargo, en odontología no existen datos del desarrollo de esta área, lo que hace difícil un seguimiento o diseño de políticas. El objetivo de este estudio, siendo una primera aproximación a la temática, es definir el perfil bibliométrico de la investigación asociada a la bioingeniería de tejidos dentales a nivel mundial en la base de datos MEDLINE para el periodo 2000-2011. Metodología: Estudio bibliométrico. Se incluyeron todos los artículos asociados a los términos “stem cells” y “tooth regeneration” para el periodo 2000-2011, indexadas en MEDLINE. Se analizaron las variables: año de publicación, país de origen, idioma y tipo de publicación (original o revisión), revista, autor, universidad de afiliación y origen del tejido utilizado (humano o animal). Resultados: Para todo el período en estudio se hallaron 257 artículos: 149 trabajos de originales publicados en inglés, 5 en otros idiomas; 92 revisiones de literatura en inglés y 9 en otros idiomas; y 2 publicaciones en categoría otros. Los países más productivos fueron Estados Unidos (24,51 por ciento), Japón (20,62 por ciento), China (17,90 por ciento), el único latinoamericano es Brasil (3,9 por ciento). El 59,09 por ciento utilizó tejidos de origen animal. Los autores más productivos fueron Ueda M (17) y Jin Y (11), en universidades fueron Fourth Military University (13), University of Tokyo (12) y Capital Medical University (10). Conclusión: Estados Unidos, Japón y China concentran dos tercios de la producción, Brasil es el único representante latinoamericano.