Biomimetic Electroconductive Nanofibrous Matrices for Skeletal Muscle Regenerative Engineering

Background: The regeneration of the muscles of the rotator cuff represents a grand challenge in musculoskeletal regenerative engineering. Several types of matrices have been proposed for skeletal muscle regeneration. However, biomimetic matrices to promote muscle regeneration and mimic native muscle tissue have not been successfully engineered. Besides topographical cues, an electrical stimulus may serve as a critical cue to improve interactions between materials and cells in scenarios fostering muscle regeneration. In this in vitro study, we engineered a novel stimulus-responsive conductive nanocomposite matrix and studied its ability to regulate muscle cell adhesion, proliferation, and differentiation. Electroconductive nanocomposite matrices demonstrated tunable conductivity and biocompatibility. Under the optimum concentration of conductive material, the matrices facilitated muscle cell adhesion, proliferation, and differentiation. Importantly, aligned conductive fibrous matrices were effective in promoting myoblast differentiation by upregulation of myogenic markers. The results demonstrated a promising potential of aligned conductive fibrous matrices for skeletal muscle regenerative engineering. Lay Summary: Around 40% of the human body mass consists of skeletal muscle. Musculoskeletal disorders such as muscle atrophy and fatty infiltration after rotator cuff injury lead to disability and pain and increase the rate of retear after rotator cuff surgery. The study showed the potential of novel engineered matrix to regenerate skeletal muscle by utilizing conductive material and nanofiber-based matrices. The incorporation of conductive material and aligned nanofibers as electrical and topographical cues significantly impacted cell viability and differentiation to support muscle regeneration. Future Work: The study demonstrated that electroconductive nanocomposite matrix can favorably modulate myoblast proliferation and differentiation. Future study will investigate the in vivo efficacy of the engineered matrix using a rat rotator cuff tear model to understand the ability of the engineered matrix in reducing the fatty infiltration.