Abstract

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.