Functional Skeletal Muscle Regeneration Using Muscle Mimetic Tissue Fabricated by Microvalve-assisted Coaxial 3D Bioprinting.

The three-dimensional (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-printer have been studied, it is still challenging to build a functional muscle structure. We propose a strategy using microvalve-assisted coaxial 3D bioprinting in consideration of a functional skeletal muscle fabrication. 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. Specially, 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 AMFs (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. This article is protected by copyright. All rights reserved.