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New, biomechanically sound tendon tissue after injection of uncultured, autologous, adipose derived regenerative cells in partial Achilles tendon defects in rabbits

Schmitz, C.; Alt, C.; Wuerfel, T.; Milz, S.; Dinzey, J.; Hill, A.; Sikes, K. J.; Burton, L.; Easley, J.; Stewart, H. L.; Puttlitz, C.; Gadomski, B. C.; Labus, K.; Pearce, D. A.; Maffulli, N.; Alt, E. U.

2024-02-21 bioengineering
10.1101/2024.02.18.580890 bioRxiv
Show abstract

BackgroundCurrent management options for partial tendon tears may not offer future potential to heal tissue and improve clinical results. This study tested the hypothesis that treatment of a partial rabbit common calcaneus tendon (CCT) defect with uncultured, autologous, adipose derived regenerative cells (UA-ADRCs) enables regenerative healing without scar formation, as recently observed in a biopsy of a human supraspinatus tendon. MethodsA full-thickness hole (diameter, 3 mm) was punched into the midsubstance of the right gastrocnemius tendon (GT; which is a part of the CCT) of adult, female New Zealand white rabbits. Immediately thereafter the rabbits were treated by application of an averaged 28.3x106 UA-ADRCs in 0.5 ml lactated Ringers solution (RLS) into the GT defect and surrounding tendon tissue, or underwent sham treatment. Rabbits were sacrificed either four weeks (W4) or twelve weeks (W12) post-treatment, and the CCTs were investigated using histology, immunohistochemistry and non-destructive biomechanical testing. ResultsNewly formed connective tissue was consistent with the formation of new tendon tissue after treatment with UA-ADRCs, and with the formation of scar tissue after sham treatment, at both W4 and W12 post-treatment. Biomechanical testing demonstrated a significantly higher mean percent relaxation after treatment with UA-ADRCs than after sham treatment (p < 0.05), and significant, negative correlations between the peak stress as well as the equilibrium stress and the cross-sectional area of the CCT (p < 0.05) after treatment with UA-ADRCs but not after sham treatment. ConclusionsManagement of partial tendon tears with UA-ADRCs has the potential to be truly "structure-modifying".

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