Abstract
For decades, the study of tissue-engineered skeletal muscle has been driven by a clinical need to treat neuromuscular diseases and volumetric muscle loss. The in vitro fabrication of muscle offers the opportunity to test drug-and cell-based therapies, to study disease processes, and to perhaps, one day, serve as a muscle graft for reconstructive surgery. This study developed a biofabrication technique to engineer muscle for research and clinical applications. A bioprinting protocol was established to deliver primary mouse myoblasts in a gelatin methacryloyl (GelMA) bioink, which was implanted in an in vivo chamber in a nude rat model. For the first time, this work demonstrated the phenomenon of myoblast migration through the bioprinted GelMA scaffold with cells spontaneously forming fibers on the surface of the material. This enabled advanced maturation and facilitated the connection between incoming vessels and nerve axons in vivo without the hindrance of a scaffold material. Immunohistochemistry revealed the hallmarks of tissue maturity with sarcomeric striations and peripherally placed nuclei in the organized bundles of muscle fibers. Such engineered muscle autografts could, with further structural development, eventually be used for surgical reconstructive purposes while the methodology presented here specifically has wide applications for in vitro and in vivo neuromuscular function and disease modelling.
Highlights
Skeletal muscle is a dynamic, vascularized, and innervated tissue that supports stature and all voluntary movement in the body
This study presents a simple single-material bioprinting technique to engineer functional skeletal muscle fibers capable of advanced maturation for in vivo engineered muscle modelling
After only two weeks of implantation in vivo, the engineered tissue was capable of vascular and neural integration. These results present a promising approach for rapid 3D fabrication of functional skeletal muscle constructs, with opportunities arising for both lab-based personalized neuromuscular tissue modelling and, even for clinical applications
Summary
Skeletal muscle is a dynamic, vascularized, and innervated tissue that supports stature and all voluntary movement in the body. While it has the capacity to regenerate and selfrepair from small injuries, volumetric muscle defects and genetic myopathies contribute to a significant healthcare burden [1,2]. The study of these diseases and the development of their treatments require faithful models of skeletal muscle physiology and anatomy in order to demonstrate efficacy and safety prior to translation into clinical trials [3,4]. While traditional muscle regeneration methods endeavor to recapitulate the stem cell niche in two-dimensional cultures, such techniques do not translate well to the fabrication of larger constructs for clinical applications [5].
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