# Novel Approaches for the Treatment of Necrotic Immutative
## 4 Discussion  
Aepeification using Ca(OH)2 or MTA is the standard treatment for NITs. However, with this technique, the treated tooth loses pulp vitality and various unfavorable consequences occur, such as the root development being interrupted. Therefore, the tooth remains with a weak root structure (an inadequate crown-to-root ratio and a high risk of fracture in the cervical root region due to functional stress) [29], which, in the long term, leads to dental extraction [30]. As an alternative option, REP has been proposed because it allows root development of these teeth. As in other endodontic procedures, disinfection is essential for the success of the procedure, which is why irrigants and intracanal antimicrobial agents are used. After that, intentional apical bleeding (BC) is induced to form a BC that serves as a cellular scaffold that promotes adequate apical healing. The BC for apical revascularization has been accepted worldwide and several reviews have shown that this therapy improves clinical success rates (97.3-93.0%). However, there is low consistency in favoring the rates of root elongation (16.1%) and the increase in root thickness (39.8%) [31]. Because of this, the postoperative root development in the NIT still represents a challenge and more efficient scaffold options have been developed. Alternative processes to BC for REP include the use of PRP and PRF. PRP is a derivative that is extracted from autologous blood, which contains three to eight times the concentration of platelets obtained by centrifugation and separation by density gradient. PRP contains several growth factors; hence its usage has been proposed in tissue regeneration [32]. Particularly in dentistry, PRP is used in the treatment of temporomandibular disorders [33], in oral and maxillofacial surgery [34], as well as in REP.  
On the other hand, PRF possesses a tetra-molecular structure that serves as a natural autologous scaffold; it is obtained as a secondary platelet concentrate composed of cells such as leukocytes, stem cells, and platelets, in addition to soluble mediators such as interleukins. This natural scaffold supports micro-vascularization and works as a transport for carrying and differentiating macrophages M2, essentials for tissue regeneration and revascularization [35]. This PRF has mechanical properties and remodeling properties, which resemble the BC. However, there is insufficient information about the effectiveness of PRF and PRP in NIT; most of the research regarding the topic are case reports, case series [36; 37], and just a few clinical trials with a small sample. [PERSON] et al. reported in a systematic review and meta-analysis that the mean success rate for apical reduction or closure was 85.1% for PRP, 85.2% for PRF, and 58.8% for BC with a follow-up of one year. On the other hand, the mean success rate for root lengthening was 64.1% for BC, 64.2% for PRP, and 74.1% for PRF. Besides, dental wall thickening was 100% for BC, 100% for PRP, and 100% for PRF. The majority of effects were similarly effective between the treatments ([PERSON]'s exact test, \(p>0.05\)) except for the apical closure that occurred more frequently following PRP and PRF compared to BC ([PERSON]'s exact test, \(p<0.0011\)) [38]. However, there is a lack of external validity in the meta-analysis. One important point is that in the included studies was that the populations are not sufficiently representatives. Further, the report does not include the impact of each study in the overall estimate, neither does the heterogeneity test with I2. There is not an analysis of the demography, treatments, or other methodological aspects that could act in favor of the intervention. Further, most of the included studies are case reports or case series that exhibited a lack of internal validity. In the present review, it was possible to carry out the meta-analysis in the clinical success and IRL outcomes because the other outcomes exhibited very heterogeneous methodologies and units of measurement that prevent pooled data.