Mechanical Loading Improves Engineered Tendon Formation with Muscle-Derived Cells: An In Vivo Analysis

The authors' previous study showed that muscle-derived cells could regenerate strong engineered tendon with better tissue structure. However, little was known about the mechanism of neotendon built by muscle-derived cells, and the development and maturation of the cells. The authors hypothesized that mechanical loading modulated this process. The aim of this study was to investigate whether mechanical loading could regulate muscle-derived cell-based engineered tendon formation and maturation.

Muscle-derived cells were isolated, expanded, and seeded onto polyglycolic acid 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 and 24 weeks after implantation, histologic examinations, ultrastructure, and biomechanical characteristics were evaluated.

Gross observation results showed that under mechanical loading, neotendon 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 morphologic cells were observed on histologic examination under mechanical loading. In contrast, the nonload group failed to form neotendon, but formed disorganized fibrous tissue with significantly worse mechanical properties and poor collagen fibril structure.

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 neotendon regeneration, stress deprivation resulted in a distinctly inferior maturity level of engineered tendon.