## 2 Neovascularization in Tendon Disorders and Its Therapeutic Potential
The question arises as to whether the neovascularization found in these studies reflected a physiological or a pathological response. This is especially interesting considering a surprising phenomenon observed in the tendinous tissue of smokers. It indicates that cigarette smoking inhibits the neovascularization process [21; 35]. Although neovascularization in smokers was deeply reduced, it did not correlate with the clinical outcomes. It clearly shows that microscopic evaluation of the new vessel formation may not be fully comparable with clinical parameters of patients. [PERSON] et al. suggested that the complete lack of vascularity in the obtained pathological tendons, as well as the excessive expansion of new capillaries, should be graded as extreme pathology in the histopathological score--the Bonar scoring system [36]. Tendinous tissue after the injury requires the regeneration process, which consists of three main phases, while the most intensive neoangiogenesis is observed in the formation phase [2]. Tendons in response to hypoxia secrete angiogenic growth factors that induce the growth of neovessels [20; 37; 38]. However, in tendinopathy, we can observe that this mechanism fails, which results in an impaired delivery of oxygen and nutrients, which are required for tissue regeneration. The ECM regulates the topology and elongation of vessels, using the proteases to form the area for new capillaries [39]. Interestingly, some authors observed that angiogenesis is significantly reduced in the areas of the tendinous tissue with the increased production and aggregation of non-collagenous ECM (glucosaminoglicans and mucopolisacharides) [21; 40]. [PERSON] et al. using a 3D angiogenesis model showed that glycosaminoglycan accumulation impaired the biological activity of vascular endothelial growth factor (VEGF) [41]. [PERSON] et al. also revealed that non-collagenous components of the ECM inhibit VEGF receptor signaling [42]. VEGF, the major role of which is related to the stimulation of the angiogenesis process, is elevated after the inflammatory phase, during the formation and remodeling phases [7]. Studies in cancer biology or retinopathy revealed that hypoxia-induced newly formed capillaries are hyperpermeable and characterized by impaired perfusion [20; 37]. In turn, in tendinopathy, the immaturity of vessels may be responsible for persisting hypoxia within regions of neovascularization [20; 37]. From a clinical research perspective, neovascularization can be defined in different ways. The summarized definitions and clinical implications are presented in Table 1.  
The experimental evidence that growth factors in platelets enhance the recruitment, proliferation, and differentiation of cells involved in tissue regeneration allowed for the widespread use of PRP in the therapy of tendinopathy [46]. The potential effect of PRP on neovessels has already been extensively studied in Achilles tendinopathy [5]. Based on these studies, it was suggested that the formation of neovessels is related to the release of VEGF as a potential angiogenic trigger factor. [PERSON] et al. assessed the