Mechanical Stimulation of Scaffold-Free, Cell-Based Single Fibers for Tissue Engineered Tendon

The clinical demand for tendon replacements following injury, surgical excision, or disease drives current tissue engineering endeavors. Great strides have been made in producing functional tissues, but none have gained clinical acceptance. Scaffold-free and cell-based engineered tissue constructs allow the use of autologous cells and avoid potential scaffold-based complications such as immune rejection and breakdown byproducts. However, scaffold-free approaches have yet to replicate the mechanical properties of tendon [1,2]. In an effort to mimic some key aspects of in vivo embryonic tendon development, such as high cellularity and subsequent cell-to-cell contact, we have utilized a cell-based and scaffold-free method to direct fibroblast cell growth through geometric constraint to form single fibers [3,4]. Early application of mechanical cues (within hours of cell attachment) is essential for cell and collagen fiber alignment, as well as tissue maturation through matrix protein synthesis, and perhaps most importantly, these structural changes will result in altered mechanical properties. We recently established a method to apply mechanical stimulation to developing scaffold-free, cell-based fibers with the goal of replicating tenogenic development cues [5]. As an important step towards scaffold-free tendon replacements, the objective of this study was to demonstrate the influence of dynamic mechanical cues on growing fibers, which can ultimately be optimized to achieve tendon-like structure and mechanical properties.