Person:

McNamara, Stephanie

While mechanical stimulation is known to regulate a wide range of biological processes at the cellular and tissue level, its medical use for tissue regeneration and rehabilitation has been limited by the availability of suitable devices. Here we present a mechanically active gel-elastomer-nitinol tissue adhesive (MAGENTA) that generates and delivers muscle contraction mimicking stimulation to a target tissue with programmed strength and frequency. MAGENTA consists of shape memory alloy spring that enables actuation up to 40% strain, and an adhesive that efficiently transmits the actuation to the underlying tissue. MAGENTA activates mechanosensing pathways involving yes-associated protein (YAP) and myocardin related transcription factor A (MRTFA) and increases the muscle rate of protein synthesis. Disuse muscles treated with MAGENTA exhibit greater size and weight, and generate higher forces compared to untreated muscles, demonstrating prevention of atrophy. MAGENTA has thus promising applications in the treatment of muscle atrophy and regenerative medicine.

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.