Collagen Scaffold Viscoelasticity Regulates Muscle Cell Phenotype

Current biomaterial strategies are typically unable to return skeletal muscle to pre‐injury function following damage, resulting in permanent loss of muscle function. Recently, there has been a growing appreciation for the role of matrix viscoelasticity in regenerative processes, and here we address the hypothesis that changes in matrix viscoelasticity regulate muscle cell function. Using norbornene‐modified type I collagen hydrogels with a tetrazine‐based crosslinker, it is found that myoblast spreading, proliferation, and differentiation are improved on and within slow‐relaxing hydrogels. However, satellite cell stemness is maintained only with soft, fast‐relaxing hydrogels. This indicates that there is a direct link between the viscoelasticity of collagen‐based substrates and muscle cell phenotype in vitro. Together, these studies further the understanding of the role of tissue mechanical properties in directing muscle cell function and provide a tool for guiding specific behaviors necessary for muscle regeneration.