Tendon tissue engineering: biomechanical considerations

Engineered soft tissue products—both tendon and ligament—have gained tremendous interest in regenerative medicine as alternatives to autograft and allograft treatments due to their potential to overcome limitations such as pain and donor site morbidity. Tendon engineered grafts have focused on the replication of native tendon tissue composition and architecture in the form of scaffolds using synthetic or natural biomaterials seeded with cells and factors. However, these approaches suffer due to static culture environments that fail to mimic the dynamic tissue environment and mechanical forces required to promote tenogenic differentiation of cultured cells. Mechanical stimulation is sensed by cellular mechanosensors such as integrins, focal adhesion kinase, and other transmembrane receptors which promote tenogenic gene expression and synthesis of tendon extracellular matrix components such as Type I collagen. Thus, it is imperative to apply biological and biomechanical aspects to engineer tendon. This review highlights the origin of tendon tissue, its ability to sense forces from its microenvironment, and the biological machinery that helps in mechanosensation. Additionally, this review focuses on use of bioreactors that aid in understanding cell-microenvironment interactions and enable the design of mechanically competent tendon tissue. We categorize these bioreactors based on functional features, sample size/type, and loading regimes and discuss their application in tendon research. The objective of this article is to provide a perspective on biomechanical considerations in the development of functional tendon tissue.