Polymeric Scaffolds for Dental, Oral, and Craniofacial Regenerative Medicine.

Dental, oral, and craniofacial (DOC) regenerative medicine aims to repair or regenerate DOC tissues including teeth, dental pulp, periodontal tissues, salivary gland, temporomandibular joint (TMJ), hard (bone, cartilage), and soft (muscle, nerve, skin) tissues of the craniofacial complex. Polymeric materials have a broad range of applications in biomedical engineering and regenerative medicine functioning as tissue engineering scaffolds, carriers for cell-based therapies, and biomedical devices for delivery of drugs and biologics. The focus of this review is to discuss the properties and clinical indications of polymeric scaffold materials and extracellular matrix technologies for DOC regenerative medicine. More specifically, this review outlines the key properties, advantages and drawbacks of natural polymers including alginate, cellulose, chitosan, silk, collagen, gelatin, fibrin, laminin, decellularized extracellular matrix, and hyaluronic acid, as well as synthetic polymers including polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), poly (ethylene glycol) (PEG), and Zwitterionic polymers. This review highlights key clinical applications of polymeric scaffolding materials to repair and/or regenerate various DOC tissues. Particularly, polymeric materials used in clinical procedures are discussed including alveolar ridge preservation, vertical and horizontal ridge augmentation, maxillary sinus augmentation, TMJ reconstruction, periodontal regeneration, periodontal/peri-implant plastic surgery, regenerative endodontics. In addition, polymeric scaffolds application in whole tooth and salivary gland regeneration are discussed.

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.

Whole-Tooth Regeneration by Allogeneic Cell Reassociation in Pig Jawbone.

IMPACT STATEMENT: The methods developed in this study to manipulate pig tooth germ cells in vitro and in vivo provide a reference for studying whole-tooth regeneration and tooth development in large animals. Of importance, compared with conventional ectopic tooth regeneration, conducted in the omentum, subcutaneous tissues, or kidney capsule (among other locations) with low with immune reactivity in rodent models, this study achieved orthotopic regeneration and development of whole teeth in a large mammal, representing a large stride toward the realization of tooth regenerative therapy for humans with missing teeth.

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.

Whole Tooth Regeneration as a Future Dental Treatment.

Dental problems caused by dental caries, periodontal disease and tooth injury compromise the oral and general health issues. Current advances for the development of regenerative therapy have been influenced by our understanding of embryonic development, stem cell biology, and tissue engineering technology. Tooth regenerative therapy for tooth tissue repair and whole tooth replacement is currently expected a novel therapeutic concept with the full recovery of tooth physiological functions. Dental stem cells and cell-activating cytokines are thought to be candidate approach for tooth tissue regeneration because they have the potential to differentiate into tooth tissues in vitro and in vivo. Whole tooth replacement therapy is considered to be an attractive concept for next generation regenerative therapy as a form of bioengineered organ replacement. For realization of whole tooth regeneration, we have developed a novel three-dimensional cell manipulation method designated the "organ germ method". This method involves compartmentalisation of epithelial and mesenchymal cells at a high cell density to mimic multicellular assembly conditions and epithelial-mesenchymal interactions in organogenesis. The bioengineered tooth germ generates a structurally correct tooth in vitro, and erupted successfully with correct tooth structure when transplanted into the oral cavity. We have ectopically generated a bioengineered tooth unit composed of a mature tooth, periodontal ligament and alveolar bone, and that tooth unit was engrafted into an adult jawbone through bone integration. Bioengineered teeth were also able to perform physiological tooth functions such as mastication, periodontal ligament function and response to noxious stimuli. In this review, we describe recent findings and technologies underpinning whole tooth regenerative therapy.