Mechanical loading improve engineered tendon formation with muscle derived cells: an in vivo analysis

Background: Our previous study showed that muscle-derived cells could regenerate strong engineered tendon with better tissue structure. However, little was known about the mechanism of neo-tendon built by muscle-derived cells, and the development and maturation of the cells. We hypothesized that mechanical loading modulated this process. The aim of this study is to investigate whether mechanical loading could regulate muscle-derived cells engineered tendon formation and maturation. Methods: Muscle-derived cells were isolated, expanded and seeded on polyglycolic acid (PGA) fibers that formed a cell-scaffold complex. After in vitro culture for 2 weeks, half of them were implanted without loading and the other half were sutured to mouse fascia that could provide a natural dynamic loading. At 12 weeks and 24 weeks after implantation, histological examinations, ultrastructure and biomechanical characteristics were evaluated. Results: Gross observation results showed that under mechanical loading neo-tendon tissue could be generated with muscle-derived cells and the tissue structure became more mature with the increase of culture time. Well-organized aligned collagen fibers and elongated morphological cells were observed in histology under mechanical loading. In contrast, the non-load group failed to form neo-tendon, but formed disorganized fibrous tissue with significantly worse mechanical properties and poor collagen fibril structure. Conclusions: This study demonstrates that mechanical loading is indispensable in tendon tissue engineering with muscle-derived cells. Although muscle-derived cells have a potential advantage in neo-tendon regeneration, stress deprivation resulted in a distinctly inferior maturity level of engineered tendon. 1 Authors who contributed equally Disclosure: The authors have no commercial associations that might pose or create a conflict of interest with the information presented in this article. ACKNOWLEDGMENTS: This study was supported by National Natural Science Foundation of China (31300807), Beijing Natural Science Foundation (7144239) and Research Fund for the Doctoral Program of Higher Education of China (20131106120015). Corresponding author: Yuanbo Liu, M.D., Department of Plastic and Reconstructive Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 33 Ba-Da-Chu Road, Beijing 100144, PR China. E-mail addresses: ybpumc@sina.com (Yuanbo Liu) ©2018American Society of Plastic Surgeons

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