Biomimetic Conductive Hydrogel Scaffolds with Anisotropy and Electrical Stimulation for In Vivo Skeletal Muscle Reconstruction

Abstract The nature of the hydrogel scaffold mimicking extracellular matrix plays a crucial role in tissue engineering like skeletal muscle repair. Herein, an anisotropic and conductive hydrogel scaffold is fabricated using gelatin methacryloyl (GelMA) as the matrix hydrogel and silver nanowire (AgNW) as the conductive dopant, through a directional freezing technique for muscle defect repair. The scaffold has an anisotropic structure composed of a directional longitudinal section and a honeycomb cross‐section, with high mechanical strength of 10.5 kPa and excellent conductivity of 0.26 S m⁻¹. These properties are similar to native muscle extracellular matrix (ECM) and allow for cell orientation under the guidance of contact cues and electrical stimulation synergistically. In vitro experiments show that the scaffold's oriented structure combined with electrical stimulation results in enhanced myotube formation, with a length of up to 863 µm and an orientation rate of 81%. Furthermore, the electrically stimulated scaffold displays a promoted muscle reconstruction ability when transplanted into rats with muscle defects, achieving a muscle mass and strength restoration ratio of 95% and 99%, respectively, compared to normal levels. These findings suggest that the scaffold has great potential in muscle repair applications.