## 3 Neovascularization in Meniscal Lesions and Its Therapeutic Potential  
Menisci are a vital contributor to proper knee joint congruence and kinematics. Thus, it is suggested that the absence of the meniscus inevitably leads to cartilage lesion and the development of osteoarthritis [54]. Restoration of meniscal integrity is thought to be an essential step in joint preservation surgery. The role of menisci in the knee joint is complex. It is responsible for load transmission, shock absorption, proprioception, articular cartilage nutrition, lubrication, and protection [55; 56; 57; 58]. Meniscal tissue consists of cells suspended in an ECM composed mainly of collagen (type 1), glycoproteins, proteoglycans, and elastin [44]. The disruption in collagen type 1 architecture with progressive loss of proteoglycans are signs of the meniscal degeneration [59]. There is a strong relationship between meniscus degeneration and articular cartilage damage, which inevitably leads to the development of osteoarthritis (OA) [60]. The meniscectomy in osteoarthritis (OA) can lead to a reduction in pain; however, the exact mechanisms are not yet established [44; 61]. [PERSON] et al. indicated that the nerve fibers and endings were localized in the menisci with concomitant capillary vessels mainly in the outer third portion of the meniscus [62]. Moreover, some studies clearly showed the variations in vascularization and the innervation of the meniscus; however, it is uncertain what is responsible for this phenomenon [63]. The healing potential of the meniscus depends on the blood supply. Blood vessels mainly origin from the medial and lateral geniculate arteries. However, in the mature skeleton, only the peripheral 10-25% of the meniscus receives blood supply from vessels attached to the synovial membrane [45]. This area is called the red-red zone [56]. The inner 10-25% of the meniscus is called the white zone and is nourished by diffusion from the synovial fluid. The transient central region of the meniscus is called the red-white region and has features of each zone. Former recommendation advised suturing menisci only in the red-red zone, but [PERSON] et al. proved that the meniscus also has regenerative potential in the hypovascular zone, with an 86% rate of healed menisci in the red-white zone [64]. [PERSON] et al. investigated the prevalence of vascular and neural ingrowth in OA [44]. The authors observed that in knee joints with more severe arthrosis, there was more abundant collagen degeneration in the outer third of the meniscus and these regions were more vascularized. Moreover, the calcitonin gene-related peptide (CGRP)-immunoreactive nerve profiles were identified alongside blood vessels. Again, it was commonly observed in the outer third part of the meniscus [44]. The inner region of the meniscus was mostly aneural [44]. These results suggest that neoangiogenesis and concomitant nerve ingrowth may contribute to pain in knee OA [44, 65]. On the other hand, the neovascularization in the meniscus may be a regenerative response similar to the one observed in the tendinous tissue. The revascularization in the meniscus structure after transplantation is commonly observed and crucial to the healing process [45]. In the last decade, there has been a growing interest in using biological agents to enhance the healing of degenerative tissues in the knee joint [66, 67, 68]. The efficacy of PRP was examined in meniscal mechanisms under normal and post-traumatic inflammatory conditions in the New Zealand white rabbit model [69]. A reproducible defect on the meniscus was used to implant fibrin glue or PRP. The study showed that PRP treatment increases catabolic molecules, especially those related to inflammation, which may accelerate fibrosis instead of meniscal cartilage regeneration. In human randomized clinical trials, [PERSON] et al. showed that PRP augmentation in suturing bucket-handle meniscal tears and trephination for degenerative meniscal tears are more effective than placebo [70, 71].