EUROPEAN JOURNAL OF PAEDIATRIC DENTISTRY VOL. 21/4-2020 331 Introduction Traumas and dental caries, or variability of dentinal substrate, that compromise adhesion [Campanella, Gallusi, Nardi et al., 2020; Campanella, Gallusi, Di Taranto et al., 2020] in immature teeth may result in pulp damage through bacterial infection [Pinna et al., 2017; Libonati et al., 2019; Gallusi et al., 2020]. In these cases, the tissue also become inflamed, and necrosis can occur. As a result, odontoblast necrosis disturbs root development [Nagata et al., 2014]. After proper and efficient endodontic manual and rotary instrumentation [Libonati et al., 2018; Severino et al., 2019; Campanella, Gianni et al., 2020], traditionally these teeth undergo apexification therapy [American Association of Endodontics,2003]. In this regard, calcium hydroxide and mineral trioxide aggregate (MTA) have been widely used to induce mineralisation and apical barrier formation [Milia et al., 2012; Pinna et al., 2015; Usai et al., 2019; Campanella, Di Taranto, et al., 2020]. However, while E. Milia*, S. Eramo**, C. D’Arcangelo***, C. Santona****, M. Beretta*****, G. Gallusi****** *Department of Medicine, Surgery and Experimental Science, University of Sassari, Sassari, Italy **Department of Surgery and Biomedical Sciences, University of Perugia, Perugia; Italy ***Department of Medical, Oral and Biotechnology Science, University of Chieti, Italy ****Dental Practitioner, Sassari, Italy *****DDS, MS Ortho, MS Digital Dentistry, Private Practice in Varese, Italy ******Department of Clinical Sciences and Translational Medicine, Dental School, University of Rome “Tor Vergata”, Rome, Italy e-mail: gianni.gallusi@gmail.com DOI: 10.23804/ejpd.2020.21.04.14 Dental pulp regeneration: An overview of the current approaches Regenerative Endodontic Procedures (REPs) are biologically based procedures aimed at restoring the damaged structures and physiological functions of the pulp-dentine complex. Clinically, two strategies have been proposed so far to induce REP: cell transplantation and cell homing. REPs success relies primarily on the clinical and biological conditions of the tooth; therefore, cell homing strategies will not be consistently successful in every condition. Root canal treatment remains the standard of care for mature teeth with necrotic pulps and closed apex. Abstract EJPD 2020 CLINICAL FOCUS Paediatric endodontics Part 2: Pulp regeneration: current approaches KEYWORDS Dental pulp regeneration; Cell transplantation; Cell homing. apexification promotes apical closure, it does not allow for root development [Damle et al., 2012]. With the aim to provide an apical healing and root maturation, tissue engineering and biotechnology have suggested biological methods [Chieruzzi et al., 2016]. Regenerative Endodontic Procedures (REPs) are biologically based procedures aimed at restoring the damaged structures and physiological functions of the pulp-dentine complex finally leading to apical closure [Eramo et al., 2018]. Nevertheless, the clinical status of the teeth in need of treatment is to be considered in order to achieve the desired outcome [Schmalz et al., 2000]. REPs are based on the combination and interplay of three key elements: appropriate cells (stem or progenitor cells), appropriate signaling molecules to regulate the cellular processes, and a matrix (scaffold) that allows for cellular growth [Diogenes et al., 2013, Schmalz et al., 2017]. In this context, the dental pulp stem cells (DPSCs), the stem cells from the apical papilla (SCAP), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), dental-follicle-derived stem cells (DFSC), and the bone marrow stem cells (BMSCs) have been largely explored [Campanella, 2018] (Table 1). Concerning the signaling molecules, a great number of molecules have been evaluated using several types of in vitro assays and animal models with the purpose to induce chemotaxis of endogenous cells, proliferation and differentiation of stem/ progenitor cells [Maioli et al., 2015; Moretti et al., 2015; Smith et al., 2016; Wang et al., 2017]. Signaling models have been mainly represented by the stromal cell-derived factor, basic fibroblast growth factor, vascular endothelial growth factor, platelet-derived growth factor, stem cell factor, and granulocyte colony-stimulating factor [Eramo et al., 2017] (Table 2). Regarding the scaffolds, they serve as transient, three-dimensional, extracellular-matrix-mimicking porous templates, which provide mechanical support and regulate cell functions [Li et al., 2005; Bottino et al., 2012]. A wide range of polymer scaffolds have been used with this purpose. Among them, synthetic (i.e. polylactic acid) and natural scaffolds (i.e. collagen), ranging from macroporous structures obtained through salt leaching/solvent casting [Cordeiro et al., 2008] and gas foaming [Huang et al., 2010], to nanofibrous scaffolds processed via electrospinning, self-assembly, and phase-separation. However, there is no single implantable scaffold that can evenly coordinate the growth and development of the different tissue types involved in the functional regeneration of the pulp-dentin complex so far.