**5. Intraarticular delivery of platelet-rich plasma**

Platelet-rich plasma (PRP; blood plasma that has been enriched with platelets) therapies have emerged as a potential approach to enhance tissue repair and regeneration, and have demonstrated to be a safe, resourceful, and effective treatment. They are based on the delivery of growth factors and cytokines from anuclear platelets that can stimulate the healing of various tissues as a consequence of activation of migratory and local cells [60, 61]. Nevertheless, because PRP is autologous, the concentration of the PRP components differs according to the physiological conditions and clinical diseases of patients [62].

The biological effects of PRP are largely attributed to the platelet secretome and some plasma signaling proteins. In fact, the α-granules of platelets within PRP release numerous growth factors and cytokines (TGF-α, TGF-β, HGF, IL-6, EGF, FGF-2, IGF-1, VEGF, and interleukin β1). Moreover, PRP contains proteases, biologically active amines, and cell adhesion molecules such as fibrin, fibronectin, and vitronectin [60]. All those molecules are involved in repair and regeneration processes, including antiapoptosis, cell proliferation, differentiation, migration, angiogenesis, and the synthesis of ECM in both normal and pathological conditions [63]. Cells within the joint add to this milieu by secreting additional biologically active molecules in response to PRP.

PRP is currently used in patients with chronic joint pain caused by progressive cartilage degeneration of the synovial joints. The anti-inflammatory effects are carried out through its effects on nuclear factor κB signaling pathway (including synoviocytes, macrophages, and chondrocytes), but also by reducing TNF-α and IL-1β [64]. A systematic review and meta-analysis related to the clinical efficacy of intraarticular PRP injection in patients with osteoarthritis have shown significant clinical improvements [65, 66].

 Recently, Kütük et al. [67] and Hegab et al. [68] reported that an intraarticular PRP injection is an effective treatment for TMJ osteoarthritis through the regeneration of fibrocartilage and cartilage, bone repair in the TMJ. Moreover, PRP has long-term analgesic effects in most patients with painful TMJ [69, 70]. Nevertheless, a randomized clinical trial in patients with TMJ osteoarthritis suggests that arthrocentesis plus PRP injections is not superior to arthrocentesis alone or combined with HA injection, and PRP does not add any significant improvement to clinical outcomes after surgery in patients with advanced internal derangement of the TMJ [71, 72]. Thus, PRP injection should not be considered as a first-line treatment for TMD, and arthrocentesis plus HA injection would appear to be more acceptable [73]. Nevertheless, other authors observed that PRP performed well than HA in the treatment of TMJ osteoarthritis in terms of pain reduction for the treatment of reducible disc displacement of the TMJ [68, 72, 74]. Future studies will focus on the synergistic actions of HA and PRP in the treatment of TMJ osteoarthritis as in other joints.
