# Novel Approaches for the Treatment of Necrotic Immutative
## 1 Introduction  
Apecification used to be the conventional treatment used for necrotic immature teeth (NIT). However, the characteristics of these teeth, which are fragile due to the thin thickness of the root canal dentin, together with the anatomy of an open apex, make it difficult to properly instrumentation, and complete canal obturuation without exceeding the periapical tissues [1]. Since the 1960s, it has been reported that the induction of apical closure due to the formation of hard tissue was achieved by the closure of the root canal using a plug containing calcium hydroxide (Ca(OH)2). To explain that phenomena, it was hypothesized that the epithelial cell rests of Malassez persist throughout life and are capable of resuming the formation of mineralized tissue on the root surface once the source of infection has been removed [2]. However, there are long-term effects of the aforementioned techniqueusing Ca(OH)\({}_{2}\) for NIT treatment. Its disadvantages have been widely debated in the literature, as the need for several material replacements, with the consequent possibility of recontamination of the root canal during the treatment period and the weakening of the root dentin [3]. Another concern was that Ca(OH)\({}_{2}\) could cause damage to the undifferentiated cells present in the ligament or the remnants of mesenchymal tissue, and preventing the root maturation [4]. On the other hand, recently, the introduction of the regenerative endodontic procedures (REPs) implies the induction of a blood clot (BC) which could allow apical revascularization, and would lead to a subsequent apical closure. However, the idea of placing a plug of some material on a BC implies the reconsideration of certain well-established endodontic principles; likewise, the procedure to generate such as a clot (inserting a file beyond the apical radiographic limits) involves that endodontic paradigm changes [5]. Due to this, REP has emerged as an alternative for the treatment of NIT. The goal of REP for the treatment of NIT is to provide a convenient microenvironment for the reestablishment of a rich blood supply and stem cells that allow the root healing [6]. This is possible to achieve due to the fast that the apical papilla and its rich resident stem cell population are capable of surviving infection and advanced apical periodontitis [7]. In REP, the periapical tissues are intentionally damaged to promote bleeding and a fibrin clot acts as a natural scaffold allowing the proliferation and differentiation of dentin-pulp stem cells [8]. Unlike traditional apexification or the use of apical barriers, the success of REP allows increasing both the length of the root and the thickness of the dentin root walls. The vascularization is crucial for the supply of the cells and the scaffolds inside the root canal and for that reason, it is important to cause enough bleed. An adequate BC also prevents the sealing material from collapsing. In addition to BC, it has been postulated that the use of the scaffolds is crucial because it provides a structural organization for stem cells to distribute, proliferate, and differentiate into odontoblasts-like cells [9]. Therefore, recent research has focused on examining different scaffolding models for REP. However, given the range of possibilities, it is important to consider the clinical success of the different scaffolds. REP should be carried out based on evidence-based dentistry. Several reviews of the literature have been published to date, however, the included studies come from case series, clinical cases, or observational studies with very small samples (less than ten participants), which directly impacts the reliability of the conclusions. On the other hand, these reviews also did not present the assessment of risk of bias and the quality assessment of the included studies, as well as a quantitative analysis.