## 4 Discussion
used Bevacizumab in Achilles tendon therapy; all authors observed improved regeneration of the tissue, established by the Bonar scoring system [1; 39; 40; 53]. Moreover, [PERSON] et al. observed superior biomechanical and histological outcomes in animals treated simultaneously with scaffold and TGF-\(\beta\)[44]. [PERSON] et al. transplanted ASCs, as a progenitor population to fibroblasts, into the injury site and observed improved tendon repair and the prevention of ectopic ossification [52]. On the other hand, [PERSON] et al. and [PERSON] et al. presented a negative influence on tendon regeneration of excessive stress and inferior histopathological outcomes measured using the Bonar system [35; 45]. Further, Isotretinoin, Tanexamic acid, and a low dose of Collagen showed a negative effect on the tendon healing process, leading to more advanced degeneration than that in control groups [34; 36; 37]. Regarding the applied evaluation method, most of the authors used the four-variable Bonar score. However, three authors introduced a fifth variable representing tenocyte proliferation and counted the number of tenocytes. This alteration was also used in the quantification of pathology in tendons tissue with the Bonar scale; nevertheless, this fifth variable should be reconsidered in further human studies [60; 61]. Unfortunately, the number of microscopic investigators in presented studies was often not available or it was a single observer. In the studies of degeneration supported with the Bonar scale, two observers or at least one experienced investigator ensure the objective assessment of tissue [25]. Still, it is not clear how it should be set for human studies. However, the use of two observers is the best solution to avoid bias. The majority of authors were unable to set a certain area of microscopic investigation. This problem was also met in studies of tendon pathology, and authors usually randomly selected the evaluated area of the slide. Regarding additional staining, the most frequent were Alcian Blue and Masson Trichrome methods, which are used for better visualization of ECM alterations. These additional stainings facilitate microscopic assessment of the tendon structure; however, none of the authors proved the necessity of these upgrades. The role that the neovascularization process plays in tendon degeneration and healing is ambiguous; thus, this variable in the Bonar scoring system should be treated with caution [62; 63; 64]. [PERSON] et al. showed that ASCs induced the neovascularization process in the early phase of Achilles tendon healing [52]. Moreover, [PERSON] et al. revealed similar scores for the neovascularization variable in both the PRP-treated group and the control group, despite the significant improvement in the overall Bonar score of subjects who underwent PRP treatment [46]. Furthermore, [PERSON] et al. noticed no statistically significant effect on vascularity in the early phase after local or systematic administration of EPO [49]. EPO is a strong proangiogenic agent, while angiogenesis is crucial in tendon healing. Authors in the late period observed statistically significant differences between locally injected EPO (0 points in Bonar) and both systematically injected EPO and the control group (both 1.33 points in Bonar). They suggested that local EPO administration contributes to vascularization in the late period. However, the vascularization score corresponded to randomly scattered, inconspicuous capillaries. It could be concluded that the EPO application provided a faster reorganization of the angiogenesis process in tendons tissue. New vessel formation is a characteristic feature of the formation phase of the tendon regeneration process which lasts approximately from the 7-8 th day until the third week. On the contrary, the invasion of new vessels is known as a typical sign of tendinopathy and often treated using sclerosing drugs [64]. In turn, [PERSON] et al.