Self-curling 3D oriented scaffolds from fish scales for skeletal muscle regeneration

Abstract Background Volumetric muscle loss (VML) due to various reasons may cause motor dysfunction and tissue engineering has been proposed for muscle regeneration. However, developing three-dimensional (3D) tissue-engineered scaffolds that can mimic oriented cell growth of muscle tissues are challenging for regeneration medicine. Herein, we propose a novel self-curling 3D oriented scaffold (SCOS) composed of fish derived gelatin methacrylate (GelMA) and fish scales for repairing skeletal muscles. Methods Fish scales of tilapia were decellularized and decalcified. Then, SCOSs were constructed by ultraviolet-coating methylated fish gelatin on the back of fish scales. C2C12 myoblasts were cultured on SCOSs, and after induction of myogenic differentiation, SCOS/C2C12 transplants were prepared for in vivo experiments. Results Decellularized and decalcified fish scales (DDFSs) became soft and retained the original oriented microgroove surface structure that could induce oriented cell growth. SCOSs could self-curl into 3D structures when immersing in culture medium due to different swelling properties of fish GelMA and DDFSs. Cell experiments demonstrated that SCOSs enhanced the oriented growth and myogenic differentiation of C2C12 myoblasts. By integrating SCOSs and myogenic differentiated C2C12 myoblasts, the resultant SCOS/C2C12 transplants promoted de novo muscle regeneration and functional restoration of muscle activity in the mouse model of VML. Conclusions Our results suggest that SCOSs loaded with myogenic differentiated C2C12 myoblasts can promote muscle regeneration in mice with skeletal muscle injuries, indicating application prospects of such scaffolds in muscle tissue engineering and other related fields.