Complete mid-portion rupture of the rat achilles tendon leads to remote and time-mismatched changes in uninjured regions

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EXPERIMENTAL STUDY

Complete mid‑portion rupture of the rat achilles tendon leads to remote and time‑mismatched changes in uninjured regions Flávio Santos da Silva1   · Bento João Abreu2   · Bengt I. Eriksson3   · Paul W. Ackermann4,5  Received: 7 April 2020 / Accepted: 14 August 2020 © European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2020

Abstract Purpose  To examine healing adaptations over 17 weeks post Achilles tendon (AT) rupture in the injured region (IR) compared to an uninjured region (UIR) of the AT. Methods  Twenty-four rats were subjected to a complete right-sided AT rupture, while the left side served as a control. ATs were harvested at 1, 2, 8 and 17 weeks post-rupture and stained with antibodies specific to Collagen type I (Col I) and II (Col II) as well as Alcian Blue and Picrosirius Red staining techniques. Histopathological changes, proteoglycan content, collagen alignment and immunoexpression were assessed. Results  Both regions examined, IR and UIR, exhibited over weeks 1–17 similar healing adaptations of increasing collagen alignment, decreasing Col I immunoexpression, as well as increasing proteoglycan content and Col II occurrence. Increased proteoglycan content was found already at week 2 in the UIR, while it first increased at week 8 in the IR. The area positive to Col II was increased compared to controls at week 8 in the UIR, whereas it first raised at week 17 in the IR. Collagen disorganization successively declined to reach control levels at week 17 in the UIR, but was still higher in the IR. Conclusion  This study demonstrated that uninjured areas of the AT remote from the rupture site also undergo pronounced remodeling, although with time-span differences relative to injured AT portions. These changes including the pathologic heterotopic mineralization and chondrogenic differentiation observed in both regions may have implications in the choice of rehabilitation regimes in order to prevent secondary rupture. Keywords  Tendon healing · Ossification · Chondrogenesis · Repair

Introduction * Paul W. Ackermann [email protected] https://medarbetare.ki.se/people/pauack Flávio Santos da Silva [email protected] Bento João Abreu [email protected] Bengt I. Eriksson [email protected] 1



Department of Health Sciences, Federal University of the Semiarid Region, Mossoró, Brazil

2



Department of Morphology, Federal University of Rio Grande do Norte, Natal, Brazil

3

Gothenburg University, Gothenburg, Sweden

4

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

5

Department of Orthopedic Surgery, Karolinska University Hospital, 17176 Stockholm, Sweden



Tendons are soft and dynamic connective tissues responsible for transmitting muscle forces to bone in order to perform movement. The Achilles tendon (AT) is the largest tendon in the human body and it is able to withstand loads greater than 12 times the body weight [22]. However, the AT is also found among the most commonly injured tendons [16] and AT tendinopathies may