The biophysical, biochemical, and biological toolbox for tenogenic phenotype maintenance in vitro

Tendon injuries constitute an unmet clinical need, with 3 to 5 million new incidents occurring annually worldwide. Tissue grafting and biomaterial-based approaches fail to provide environments that are conducive to regeneration; instead they lead to nonspecific cell adhesion and scar tissue formation, which collectively impair functionality. Cell based therapies may potentially recover native tendon function, if tenocyte trans-differentiation can be evaded and stem cell differentiation towards tenogenic lineage is attained. To this end, recreating an artificial in vivo tendon niche by engineering functional in vitro microenvironments is a research priority. Clinically relevant cell based therapies for tendon repair and regeneration could be created using tools that harness biophysical beacons (surface topography, mechanical loading), biochemical cues (oxygen tension), and biological signals (growth factors).