Alexander J. Vervaecke; Andrew D. Carbone; Adam Abraham; Zachary Bernstein; Damien Laudier; Olivier Verborgt; Leesa M. Galatz; Alice H. Huang
Journal of Shoulder and Elbow Surgery, 2022, , ISSN 1058-2746, Published: 04 June 2022
https://doi.org/10.1016/j.jse.2022.05.004
14 citations · 8 en 2025–2026
Les titres, résumés et légendes des publications sont présentés en anglais.
ABSTRACT
Background
High rates of structural failure are reported after rotator cuff repairs due to inability to recreate the native enthesis during healing. The development of biological augmentation methods that mitigate scar formation and regenerate the enthesis is still an unmet need. Since neonatal enthesis is capable of regeneration after injury, this study tested whether delivery of neonatal tendon progenitor cells (TPC) into the adult injured environment can enhance functional and structural supraspinatus enthesis and tendon healing.
Methods
TPCs were isolated from Ai14 Rosa26-TdTomato mouse Achilles tendons and labeled using Adenovirus-Cre. 52 CB57BL/6J mice underwent detachment and acute repair of the supraspinatus tendon and received either a fibrin-only or TPC-fibrin gel. Immunofluorescence analysis was carried out to determine cellularity (DAPI), fibrocartilage (SOX9), macrophages (F4/80), myofibroblasts (αSMA), and scar (laminin). Assays for function (gait and biomechanical testing) and structure (μCT imaging, Picrosirius Red/Alcian Blue staining, type I and III collagen staining) were carried out.
Results
Analysis of TdTomato cells after injury showed minimal retention of TPCs by d7 and d14, with detected cells localized near the bursa and deltoid rather than the enthesis/tendon. However, TPC delivery led to significantly increased %Sox9+ cells in the enthesis at d7 post-injury and decreased laminin intensity across almost all time points compared to fibrin-only. Similarly, TPC-treated mice showed gait recovery by d14 (paw area and stride length) and d28 (stance time) while fibrin-treated mice failed to recover gait parameters. Despite improved gait, biomechanical testing showed no differences between groups. Structural analysis by μCT suggests that TPC application improves cortical thickness after surgery compared to fibrin. Superior collagen alignment at the neo-enthesis was also observed in the TPC-augmented group at d28, but no difference detected in type I and III collagen intensity.
Conclusion
We found that neonatal TPCs improved and restored functional gait by reducing overall scar formation, improving enthesis collagen alignment and altering bony composition response after supraspinatus tendon repair. TPCs did not appear to integrate into the healing tissue, suggesting improved healing may be due to paracrine effects at early stages. Future work will determine the factors secreted by TPCs to develop translational targets.
Keywords
Rotator cuff tear; rotator cuff repair; biological augmentation; tendon progenitor cells; shoulder surgery; enthesis; scar formation; functional healing
Utilisation des équipements
L’étude comprend des essais biomécaniques après détachement et réparation du tendon supra-épineux chez des souris recevant de la fibrine seule ou des cellules progénitrices tendineuses dans un gel de fibrine. Le résumé disponible ne précise ni l’appareil d’essai, ni le mode de chargement, ni les grandeurs mécaniques mesurées. L’utilisation d’un Mach-1 Mechanical Tester ne peut être confirmée.
