## 4 Discussion
In-vitro culture studies [36; 37] and experiment comparing L-PRF and PRP gel show that the L-PRF membrane remains intact after seven days, therefore confirming that the fibrin architecture is stronger in the PRF subfamilies when compared to the PRP gel classes [38]. The extrinsic form of L-PRF as a solid dense fibrin membrane makes it a suitable biomaterial to be used as an adjunct to stimulate tissue healing and regeneration, by serving as a biological healing matrix while maintaining a slow, sustained release of growth factors and key adhesion proteins during the healing period. The ease of preparation, relatively inexpensive technique, and ability to produce high-quantity L-PRF clots simultaneously without the use of chemicals are the several advantages of L-PRF, making it a novel addition to the surgeon's arsenal in regeneration of hard and soft tissue defects. Management of necrotic defects of jawbones (both ORN and MRONJ) is often challenging. This is due to the compromised host healing process and existing tissue destruction that cannot be reversed into regeneration. The concept of using platelet concentrates is aimed at enhancing the compromised natural healing biology of the host. The slow and sustained release of mitogenic growth factors (TGF81, PDGF-AB, and VEGF) and key adhesion proteins (TSP-1, fibronectin, and vitronectin) from L-PRF play an important role in re-orchestrating the molecular cascade of healing. The therapeutic advantage of L-PRF to promote tissue regeneration is derived through the ability to restore the natural healing process by stimulating the different pathways that ultimately lead to the activation of gene expression and the production of necessary proteins for healing [39]. The PRF clot has been shown to quickly stimulate tissue healing by significantly increasing the recruitment and proliferation of a variety of cells, including endothelial cells, gingival fibroblast, chondrocytes, and osteoblast, thereby heavily promoting tissue repair and angiogenesis at site of injury [40]. These processes are regulated by local concentration of cytokines and growth factors trapped within the fibrous scaffolding. The increase of leucocytes and macrophages in the microenvironment can offer additional antibacterial defense against potential pathogens and reduce the risk of bacterial infection. Additionally, macrophages have been shown to be key mediators in osseous healing both during modeling and remodeling [41]. The biological effects of PRF in bone regeneration was investigated and proven. In a study conducted by [PERSON] et al. [42], PRF was found to increase human osteoblast attachment and proliferation by enhancing Akt phosphorylation pathway and simultaneously upregulating collagen-related protein production by increasing expression of heat shock protein 47 (HSP47) and lysyl oxidase (LOX) in human osteoblasts, resulting in increased production of a collagen matrix for bone regeneration. PRF has superior potential in promoting bone regeneration as compared to PRP. The activation of thrombin during PRP preparation resulted in large, immediate release of growth factors for a short duration, and this release could be lost in the interstitium in vivo before the onset of osteoblasts ingrowth. It was found that 81% of total TGF-81 and similar levels of total PDGF-AB are released within the first day, with significantly decreased release on the 3 rd, 7 th, and 14 th day [5; 43]. The first report on the use of platelet concentrate as a surgical adjunct in management of ORN was by [PERSON] et al. in 2011 [44]. In this case, PRP was used, successful healing of a mandibular ORN was observed, and the beneficial effects of PRP on healing of ORN was described. However, results from a double blinded randomized controlled trial failed to show any benefit of PRP in the prevention of ORN [45]. There is a paucity of high-level evidence data in the therapeutic value of platelet concentrate as surgical adjunct in the management of ORN.