Engineering the Tenogenic Niche In Vitro with Microenvironmental Tools

Tendon injuries affect millions of people worldwide annually. Considering that traditional approaches (e.g., surgery, exercise, steroid injections) have failed to reinstate tendon function following injury, recent efforts have been directed toward the development of cell‐based tendon repair and regeneration therapies. However, tenocytes readily lose their phenotype in culture and implantation of naïve stem cells is often associated with ectopic bone formation. To this end, there has been a surge in efforts to engineer the optimal tenogenic niche in vitro that will either maintain the phenotype of tenocytes or direct other cell types toward tenogenic lineage. Mono‐domain biochemical (e.g., media supplements, substrate coatings, oxygen tension), biological (e.g., growth factors, co‐culture systems), or biophysical (topography, rigidity, mechanical stimulation, macromolecular crowding) cues that replicate the native tendon milieu have shown some level of success, but they have failed to provide a functional therapy. Considering the complexity of the native tissue microenvironment together with recent advances in chemistry, biology, and engineering, it is anticipated that in the years to come multifactorial approaches are likely to yield a functional cell‐based therapy for tendon repair and regeneration.