Tendons are collagen-based fibrous tissues that connect and transmit forces from muscle to bone. These tissues, which are high in collagen type I content, have been studied extensively to understand collagen fibrillogenesis. Although the mechanisms have not been fully elucidated, our understanding has continued to progress. Here, we review two prevailing models of collagen fibrillogenesis and discuss the regulation of the process by candidate cellular and extracellular matrix molecules. Although numerous molecules have been implicated in the regulation of collagen fibrillogenesis, we focus on those that have been suggested to be particularly relevant to collagen type I fibril formation during tendon development, including members of the collagen and small leucine-rich proteoglycan families, as well as other molecules, including scleraxis, cartilage oligomeric matrix protein, and cytoskeletal proteins.

Tendon repair after injury poses a significant problem due to variable success rates. Consequently, tissue engineering with stem cells has been explored to enable replacement of damaged tendon with regenerated, living tissue. Interestingly, there are no known growth factors available to induce and guide stem cell differentiation toward the tendon lineage in a tissue engineering system. This is due largely to limited understanding of the role of growth factors in tendon development. We propose to identify and characterize these candidate growth factors, and derive new growth factor-directed tendon tissue regeneration strategies. In this study, we investigated the effects of musclederived growth factors on embryonic tendon cells in an in vitro culture system. Our results demonstrated that apparent soluble muscle signaling factors downregulated proliferation, increased metabolic activity, and induced morphological changes in the ETCs. Identification of signaling molecules capable of enhancing and guiding stem cell differentiation into tendon fibroblasts and development into new tissue will lead to innovative new tendon tissue engineering strategies.