Achilles Curse and Remedy: Tendon Diseases from Pathophysiology to Novel Therapeutic Approaches

Dear Colleagues,

In Greek mythology, Achilles, the Greek hero, is almost invulnerable—except for his Achilles heel, whose injury resulted in his death. How could a tendon injury take such a prominent place in Greek mythology? This injury was obviously such a crucial and inexplicable event that it was extensively honored in the legendary Iliad of Homer. Presumably, the ancient Greeks had already asked themselves how it could have happened that the greatest tendon of man could suddenly break, even in a young, vigorous athlete. Tendons are dense connective tissues and critical components for the integrity and function of the musculoskeletal system, as they connect bone to muscle and transmit forces on which locomotion entirely depends. Due to the increasing age of our society and a rise in the engagement of young people in overuse activities or extreme sports, tendon diseases present major clinical and financial challenges in modern medicine. Inevitably, tendinopathies lead to the final stage disease that is tendon rupture, and once this happens, tendon natural healing is slow, often poorly responding to treatments and requiring prolonged rehabilitation in most cases. A major cause of tendon rupture is tendon tissue degeneration, a process that can be considered a failure of matrix adaptation and remodeling because of an imbalance between matrix decomposition and synthesis due to a variety of stresses and mechanical loads. There are three main hypotheses about the cause(s) of tendon degeneration: (1) mechanical overuse (via matrix), (2) neo-vascularization (via exogenous cells), and (3) cell and tissue aging (via endogenous cells). Most likely, all these three triggers cross-talk to and cross-react with one, another ultimately leading to the failure of the whole tendon unit. So far, there have been only a few approved treatments for tendinopathy that are targeted against specific molecular processes, and still, in most cases, there is little to no evidence of therapeutic effectiveness, especially in the long term. Regarding end-stage tendon rupture, there are two main clinical algorithms, namely, subjecting patients to surgical or conservative therapy, as both require months-long periods to achieve mostly partial and rarely full structural and functional tendon reconstitution.

Therefore, this Special Issue aims to embrace studies concentrating on endogenous tendon cells and their governing molecular pathways, the contribution of exogenous cells (vascular, inflammatory, and neuronal), and the significance of niche structural composition and biomechanical properties leading to tendon diseases, as well as studies focusing on novel tendon medicinal and tissue engineering therapeutic approaches with the overall goal to re-define the status quo in the field of tendon disease and therapy.

Prof. Dr. Denitsa Docheva
Guest Editor

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