Artikel
Longitudinal analysis of early healing events after human Achilles tendon tear
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Veröffentlicht: | 23. Oktober 2017 |
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Gliederung
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Objectives: After tendon tear, inferior scar tissue is formed and can result in a recurrent defect. The biological processes behind the inferior healing potential are so far less understood. Therefore more knowledge about the healing phases in human tendons are needed. With the present longitudinal investigation of the early human Achilles tendon healing, new insights into the temporal changes of immunological processes and formation as well as degradation of the extracellular matrix will be provided.
Methods: After local IRB approval, tendon tissue samples were collected from 40 patients (Age: 39±10) with acute Achilles tendon tears directly from the tear site. The surgery was performed 2 to 11 days after trauma and the samples were grouped accordingly: early (2-4 days; n=15), middle (5-6 days; n=15) and late (>7 days; n=10). Histological evaluations (modified Movin score) were used to determine pathologic tendon changes. The expression of immunological factors (IL-6, IL-1ß, TNF-a, IL-10, TGF-ß, Cox-2), Proteolytic enzymes (MMP-1, -2, -3, -9, -10, -13) and their inhibitors (TIMP-1 to -4) was analyzed by qRT-PCR. Statistics: Mann-Whitney-U Test, p<0.05.
Results and Conclusion: The histological score significantly increased from the early time point post tear compared to the late time point (6.5±2.3 versus 8.8±2.0), with a lower amount of aligned collagen, a higher amount of fat tissue, as well as a higher cellularity and vascularity. The expression of MMP-2, -9, and -13 significantly increased with the time after trauma, whereas the expression of MMP-3 and MMP-10 significantly decreased over time, and TIMP-1 only tended to be decreased. The expression of Col I and Col III significantly increased over time post trauma. The immunological factors were clearly expressed in the samples but without significant differences between the groups. However, independent from the time point, in some patients a strong increase in immunological factors could be detected.
The study shows for the first time alterations of important MMPs and TIMPs as well as structural tendon changes in a longitudinal human Achilles tendon tear analysis. As shown previously the same MMP regulations were found in tenocytes of supraspinatus tendons of patients with higher age and degenerative status of the tendon [Klatte-Schulz et al. 2015]. This might imply that the later the Achilles tendon surgery takes place after trauma the more the tendon tissue is turning into a degenerative milieu, which could also be confirmed by the increasing histological score and might impede tendon healing processes. Therefore, the time point of surgical intervention after trauma might be critical and should be considered to obtain an optimal functional outcome. It has to be clarified in future follow-up studies if the strong expression of immunological factors in some patients is additionally related to an inferior tendon healing outcome for the patient.