Traumatic injuries, genetic diseases and external harmful agents such as bacteria and acids often compromise tooth integrity. There is an unmet medical need to develop alternative, innovative dental treatments that complement traditional restorative and surgery techniques. Stem cells have transformed the medical field during the last years. The combination of stem cells with bioactive scaffolds and nanostructured materials turn out to be increasingly beneficial in regenerative dental medicine. Stem cell-based regenerative approaches for the formation of dental tissues will significantly improve treatments and will have a major impact in dental practice. To date there is no established and reliable stem cell-based treatment translated into the dental clinics, however, the advances and improved technological knowledge are promising for successful dental therapies in the near future. Here, we review some of the contemporary challenges in dental medicine and describe the benefits and future possibilities of certain novel approaches in the emerging field of regenerative dentistry.

INTRODUCTION – TOOTH SPECIFICITY

Teeth exert fundamental roles in physiological functions, such as mastication and speech, and are a key feature of facial aesthetics. Tooth functioning relies on its unique combination of hard and soft tissues. Enamel is the hardest tissue of the human body with exceptional physical characteristics to withstand masticatory forces and to protect dental tissues from chemical and bacterial assaults (Figure 1A). 1 Ameloblasts synthesize the organic components of enamel, where hydroxyapatite prisms are formed, but these cells are lost upon tooth eruption, making human teeth incapable of regenerating enamel. Dentin forms a less mineralized matrix tightly interconnected with the enamel and dental pulp, a richly vascularized and innervated soft connective tissue that occupies the central portion of teeth (Figure 1A). Dentin is synthesized by pulp-derived odontoblasts and is characterized by the presence of dentinal tubules that contain the cytoplasmic extensions of odontoblasts as well as sensory nerve endings, thus making dentin highly sensitive to external stimuli and permeable to bacteria upon enamel destruction. Upon tooth injury, a newly formed dentin- or bone-like matrix (i.e., tertiary dentin) protects pulp vitality, but more important damage often leads to pulp necrosis. 1 Teeth are anchored to the alveolar bone by their roots that consist of dentin and cementum. The roots are connected to the bone via the periodontal ligament, a connective tissue that provides stability to the teeth and absorbs mechanical stresses during mastication. 2 Traumatic injuries, infections and genetic diseases, combined with age, often result in tooth loss. It is therefore necessary to develop innovative approaches for the repair/regeneration of damaged or missing dental and alveolar bone tissues.3 However, the unique characteristics of enamel and dentin make tooth regeneration particularly challenging. Technological advancements ranging from digitalization to nanotechnology have become an inherent aspect of many medical fields, and the same applies to dentistry. These progresses aim to offer improved, faster, painless and more effective treatments when compared to methods traditionally used in dental clinics.