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.

Current Biomedical Applications of 3D-Printed Hydrogels

“…In muscle tissue engineering, the scaffold design may incorporate aligned fibers or microstructures to facilitate cell alignment and muscle tissue formation. Artificial muscle tissue made of GelMA and glycidyl methacrylated hyaluronic acid implanted in the anterior tibia of rats has been shown to respond to electrical stimulation and correspond to histologically regenerated muscle tissue [137]. In another study, both short-and long-term repair results have also demonstrated the ability of a scaffold made of fibrinogen and GelMA to enhance functional skeletal muscle tissue regeneration in a rat volumetric muscle-loss model [53].…”

Macrostructure and Microenvironment Biomimetic Hydrogel: Design, Properties, and Tissue Engineering Application

“…Lee et al, drawing inspiration from the structures and functions of natural skeletal muscle, employed microvalveassisted coaxial 3D bioprinting to create photo-cross-linked hydrogels that mimic muscle fascicles (Figure 16a). 218 By mimicking the complex, multilevel, and highly ordered structure of muscle tissue, the hydrogels solved the problem of cell impenetrability and the lack of cell−ECM interaction. The hydrogels exhibited a core−shell structure.…”

“…(a) Preparation of a photo-cross-linked hydrogel with microvalve-assisted coaxial 3D bioprinting for muscle repair. Reproduced from ref . Copyright 2022 John Wiley and Sons.…”

Functional hydrogels for the repair and regeneration of tissue defects

“… Alheib et al (2022) designed a laminin-biofunctionalized gellan gum hydrogel capable of loading myogenic cells for the treatment of moderate muscle injuries that exceed the ability of muscle tissue to heal itself. Hydrogels have unique bionic properties in that their three-dimensional skeletal fibres can mimic the uniaxially oriented muscle fibres of natural skeletal muscle by adjusting the synthesis strategy and manufacturing process; Lee et al (2022) successfully fabricated artificial functional skeletal muscle using photocrosslinked hydrogels with the help of Microvalve-Assisted Coaxial 3D Bioprinting for tissue reconstruction after muscle defects. Hydrogels with tissue adhesion and self-healing properties can withstand external tension, mechanical stress and fatigue during the repair of skeletal muscle; Carleton et al (2021) reported a multifunctional hydrogel (MAA-collagen) based on methacrylic acid and collagen for the treatment of volumetric muscle loss.…”