## 2 Neovascularization in Tendon Disorders and Its Therapeutic Potential  
Tendons are structures responsible for the distribution of force generated by muscles. They are designed to contribute to human body movements, stabilize joints, and absorb the shocks [6; 7; 8]. The special properties of tendons tissue allow for the high load toleration, which results mainly from the organized structure often described as \"synthetic climbing rope\" [7]. This unique construction of the tendon allows for the spreading of stress and decreases the risk of rupture [7; 9]. Tendinous tissue is classified as dense regular connective tissue formed and supported by specialized fibroblasts called tendon cells (tenocytes). The extracellular matrix (ECM), abundant with densely packed and regularly arranged collagen fibrils, forms a scaffold for tenocytes, capillary vessels, nerve endings, and creates an environment for metabolic reactions [10; 11]. Tendons are metabolically active structures, and like other tissues, they require a blood supply. However, its vascular perfusion is relatively weak compared to other types of connective tissue, such as muscles [2; 12]. In healthy tendons, vascularization is extremely limited, with a small number of capillaries localized between bundles of collagen. These capillaries arise mainly from the musculotendinous junction, osteotendinous junction, and connective tissue sheath [2]. There is a group of tendons that contain specific hypovascular regions that lead to poor regeneration and predispose the tendons to pathology [4; 6; 7; 13; 14; 15; 16; 17; 18; 19]. Moreover, these specific tendons are usually exposed to increased forces with various vectors of action, e.g., the rotator cuff tendons, the long head of the biceps tendon, Achilles tendon, posterior tibialis tendon, patellar tendon, gluteal tendons, and the tibialis anterior tendon. The excessive load acting on tendons tissue from these certain regions, in the presence of risk factors, may lead to the development of pathology--tendinopathy, which manifests microscopically as a degenerative process. The etiopathogenesis of tendinopathy indicates hypoxia and an anaerobic environment within degenerated tendinous tissue lesions [20]. These specific conditions activate the metabolic pathways to save tissue from hypoxia, and the abundant expansion of newly formed capillaries followed by the chaotic production of ECM components is observed [21; 22; 23] (Figure 1). Figure 1: Arthroscopic view of the long head of the biceps brachii muscle tendon. The neovessels in the proximal part of tendon are seen (arrows) in the patient with symptomatic tendinopathy. In the 1990s, blood flow in symptomatic tendons assessed by ultrasound (US) and power Doppler modality was described by [PERSON] et al. [24]. Hypothetically, the concomitant nerve ending ingrowth that accompanies new vessel formation is thought to be responsible for pain. Neurovascular ingrowth in painful areas of tendons has been described in a few studies [12; 25; 26; 27]. Moreover, it was supported by the detection of several sensory neurotransmitters within and around the tendons using microdialysis [28]. Additionally, [PERSON] and [PERSON] presented US-guided techniques to reduce neovascularization by injecting the sclerosants in the most abundant regions of neovascularization [29]. On the other hand, some recent studies revealed that neovascularization in tendon disorders has a mythological status and does not necessarily correspond to the clinical outcome [5; 18; 20; 21; 30; 31]. Various authors clearly showed that there is no connection between neoangiogenesis and pain [19; 30; 31]. Neovascular was also found in Achilles tendons among asymptomatic athletes [1]. Most of the studies which presented the negative impact of neovascularization were related to the Achilles tendon, but more recent research showed that neovessels are detected in 29% of asymptomatic athletes, and in 100% of subjects after strenuous exercise [1; 29; 32; 33; 34].