Functional Skeletal Muscle Regeneration Using Muscle Mimetic Tissue Fabricated by Microvalve‐Assisted Coaxial 3D Bioprinting

Abstract 3D‐printed artificial skeletal muscle, which mimics the structural and functional characteristics of native skeletal muscle, is a promising treatment method for muscle reconstruction. Although various fabrication techniques for skeletal muscle using 3D bio‐printers are studied, it is still challenging to build a functional muscle structure. A strategy using microvalve‐assisted coaxial 3D bioprinting in consideration of functional skeletal muscle fabrication is reported. The unit (artificial muscle fascicle: AMF) of muscle mimetic tissue is composed of a core filled with medium‐based C2C12 myoblast aggregates as a role of muscle fibers and a photo cross‐linkable hydrogel‐based shell as a role of connective tissue in muscles that enhances printability and cell adhesion and proliferation. Especially, a microvalve system is applied for the core part with even cell distribution and strong cell–cell interaction. This system enhances myotube formation and consequently shows spontaneous contraction. A multi‐printed AMF (artificial muscle tissue: AMT) as a piece of muscle is implanted into the anterior tibia (TA) muscle defect site of immunocompromised rats. As a result, the TA‐implanted AMT responds to electrical stimulation and represents histologically regenerated muscle tissue. This microvalve‐assisted coaxial 3D bioprinting shows a significant step forward to mimicking native skeletal muscle tissue.